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1. Evaluation of drivers of treatment switch in relapsing multiple sclerosis: a study from the Italian MS Registry

Author: Iaffaldano, P, Lucisano, G, Guerra, T, Patti, F, Cocco, E, De Luca, G, Brescia Morra, V, Pozzilli, C, Zaffaroni, M, Ferraro, D, Gasperini, C, Salemi, G, Bergamaschi, R, Lus, G, Inglese, M, Romano, S, Bellantonio, P, Di Monte, E, Maniscalco, G, Conte, A, Lugaresi, A, Vianello, M, Torri Clerici, V, Di Sapio, A, Pesci, I, Granella, F, Totaro, R, Marfia, G, Danni, M, Cavalla, P, Valentino, P, Aguglia, U, Montepietra, S, Ferraro, E, Protti, A, Spitaleri, D, Avolio, C, De Riz, M, Maimone, D, Cavaletti, G, Gazzola, P, Tedeschi, G, Sessa, M, Rovaris, M, Di Palma, F, Gatto, M, Cargnelutti, D, De Robertis̄, F, Logullo, F, Rini, A, Meucci, G, Ardito, B, Banfi, P, Nasuelli, D, Paolicelli, D, Rocca, M, Portaccio, E, Chisari, C, Fenu, G, Onofrj, M, Carotenuto, A, Ruggieri, S, Tortorella, C, Ragonese, P, Nica, M, Amato, M, Filippi, M, Trojano, M, Iaffaldano P., Lucisano G., Guerra T., Patti F., Cocco E., De Luca G., Brescia Morra V., Pozzilli C., Zaffaroni M., Ferraro D., Gasperini C., Salemi G., Bergamaschi R., Lus G., Inglese M., Romano S., Bellantonio P., Di Monte E., Maniscalco G. T., Conte A., Lugaresi A., Vianello M., Torri Clerici V. L. A., Di Sapio A., Pesci I., Granella F., Totaro R., Marfia G. A., Danni M. C., Cavalla P., Valentino P., Aguglia U., Montepietra S., Ferraro E., Protti A., Spitaleri D., Avolio C., De Riz M., Maimone D., Cavaletti G., Gazzola P., Tedeschi G., Sessa M., Rovaris M., Di Palma F., Gatto M., Cargnelutti D., De Robertis̄ F., Logullo F. O., Rini A., Meucci G., Ardito B., Banfi P., Nasuelli D., Paolicelli D., Rocca M. A., Portaccio E., Chisari C. G., Fenu G., Onofrj M., Carotenuto A., Ruggieri S., Tortorella C., Ragonese P., Nica M., Amato M. P., Filippi M., Trojano M., Iaffaldano, P, Lucisano, G, Guerra, T, Patti, F, Cocco, E, De Luca, G, Brescia Morra, V, Pozzilli, C, Zaffaroni, M, Ferraro, D, Gasperini, C, Salemi, G, Bergamaschi, R, Lus, G, Inglese, M, Romano, S, Bellantonio, P, Di Monte, E, Maniscalco, G, Conte, A, Lugaresi, A, Vianello, M, Torri Clerici, V, Di Sapio, A, Pesci, I, Granella, F, Totaro, R, Marfia, G, Danni, M, Cavalla, P, Valentino, P, Aguglia, U, Montepietra, S, Ferraro, E, Protti, A, Spitaleri, D, Avolio, C, De Riz, M, Maimone, D, Cavaletti, G, Gazzola, P, Tedeschi, G, Sessa, M, Rovaris, M, Di Palma, F, Gatto, M, Cargnelutti, D, De Robertis̄, F, Logullo, F, Rini, A, Meucci, G, Ardito, B, Banfi, P, Nasuelli, D, Paolicelli, D, Rocca, M, Portaccio, E, Chisari, C, Fenu, G, Onofrj, M, Carotenuto, A, Ruggieri, S, Tortorella, C, Ragonese, P, Nica, M, Amato, M, Filippi, M, Trojano, M, Iaffaldano P., Lucisano G., Guerra T., Patti F., Cocco E., De Luca G., Brescia Morra V., Pozzilli C., Zaffaroni M., Ferraro D., Gasperini C., Salemi G., Bergamaschi R., Lus G., Inglese M., Romano S., Bellantonio P., Di Monte E., Maniscalco G. T., Conte A., Lugaresi A., Vianello M., Torri Clerici V. L. A., Di Sapio A., Pesci I., Granella F., Totaro R., Marfia G. A., Danni M. C., Cavalla P., Valentino P., Aguglia U., Montepietra S., Ferraro E., Protti A., Spitaleri D., Avolio C., De Riz M., Maimone D., Cavaletti G., Gazzola P., Tedeschi G., Sessa M., Rovaris M., Di Palma F., Gatto M., Cargnelutti D., De Robertis̄ F., Logullo F. O., Rini A., Meucci G., Ardito B., Banfi P., Nasuelli D., Paolicelli D., Rocca M. A., Portaccio E., Chisari C. G., Fenu G., Onofrj M., Carotenuto A., Ruggieri S., Tortorella C., Ragonese P., Nica M., Amato M. P., Filippi M., and Trojano M.
Abstract: Background: Active relapsing–remitting (RR) and secondary progressive (SP) multiple sclerosis (MS) are currently defined as “relapsing MS” (RMS). The aim of this cross-sectional study was to assess drivers of treatment switches due to clinical relapses in a population of RMS patients collected in the Italian MS and Related Disorders Register (I-MS&RD). Methods: RRMS and SPMS patients with at least one relapse in a time window of 2 years before of data extraction were defined as RMS. Factors associated with disease-modifying therapy (DMT) switching due to clinical activity were assessed through multivariable logistic regression models in which treatment exposure was included as the last recorded DMT and the last DMT’s class [moderate-efficacy (ME), high-efficacy (HE) DMTs and anti-CD20 drugs]. Results: A cohort of 4739 RMS patients (4161 RRMS, 578 SPMS) was extracted from the I-MS&RD. A total of 2694 patients switching DMTs due to relapses were identified. Switchers were significantly (p < 0.0001) younger, less disabled, more frequently affected by an RR disease course in comparison to non-switcher patients. The multivariable logistic regression models showed that Alemtuzumab (OR 0.08, 95% CI 0.02–0.37), Natalizumab (0.48, 0.30–0.76), Ocrelizumab (0.1, 0.02–0.45) and Rituximab (0.23, 0.06–0.82) exposure was a protective factor against treatment switch due to relapses. Moreover, the use of HE DMTs (0.43, 0.31–0.59), especially anti-CD20 drugs (0.14, 0.05–0.37), resulted to be a protective factor against treatment switch due to relapses in comparison with ME DMTs. Conclusions: More than 50% of RMS switched therapy due to disease activity. HE DMTs, especially anti-CD20 drugs, significantly reduce the risk of treatment switch.
Published: 2023

2. Data monitoring roadmap. The experience of the Italian Multiple Sclerosis and Related Disorders Register

Author: Mosconi, P, Guerra, T, Paletta, P, D'Ettorre, A, Ponzio, M, Battaglia, M, Amato, M, Bergamaschi, R, Capobianco, M, Comi, G, Gasperini, C, Patti, F, Pugliatti, M, Ulivelli, M, Trojano, M, Lepore, V, Aguglia, U, Ancona, A, Ardito, B, Avolio, C, Balgera, R, Banfi, P, Barcella, V, Barone, P, Bellantonio, P, Berardinelli, A, Bertora, P, Bianchi, M, Bramanti, P, Brescia Morra, V, Brichetto, G, Brioschi, A, Buccafusca, M, Bucello, S, Busillo, V, Calchetti, B, Cantello, R, Capone, F, Capone, L, Cargnelutti, D, Carozzi, M, Cartechini, E, Cavaletti, G, Cavalla, P, Celani, M, Clerici, R, Clerico, M, Cocco, E, Torri Clerici, V, Coniglio, M, Conte, A, Corea, F, Cottone, S, Crociani, P, D'Andrea, F, Danni, M, De Luca, G, de Pascalis, D, De Riz, M, De Robertis, F, De Rosa, G, De Stefano, N, Della Corte, M, Di Sapio, A, Docimo, R, Falcini, M, Falcone, N, Fermi, S, Ferraro, E, Ferro, M, Fortunato, M, Foschi, M, Gajofatto, A, Gallo, A, Gallo, P, Gatto, M, Gazzola, P, Giordano, A, Granella, F, Grasso, M, Grimaldi, L, Iaffaldano, P, Immovilli, P, Imperiale, D, Inglese, M, Iodice, R, Leva, S, Leuzzi, V, Lugaresi, A, Lus, G, Maimone, D, Mancinelli, L, Maniscalco, G, Marfia, G, Margari, L, Marinelli, F, Marini, B, Marson, A, Mascoli, N, Massacesi, L, Melani, F, Merello, M, Fioretti, C, Mirabella, M, Montepietra, S, Nasuelli, D, Nicolao, P, Pasquali, L, Passantino, F, Pecori, C, Peresson, M, Pesci, I, Piantadosi, C, Piras, M, Pizzorno, M, Plewnia, K, Pozzilli, C, Protti, A, Quatrale, R, Realmuto, S, Ribizzi, G, Rinalduzzi, S, Rini, A, Romano, S, Filippi, M, Ronzoni, M, Rossi, P, Rovaris, M, Salemi, G, Santangelo, G, Santangelo, M, Leone, A, Sarchielli, P, Sinisi, L, Ferraro, D, Solaro, C, Spitaleri, D, Strumia, S, Tassinari, T, Santuccio, G, Tortorella, C, Totaro, R, Tozzo, A, Trivelli, G, Turano, G, Valentino, P, Venturi, S, Vianello, M, Zaffaroni, M, Zarbo, R, Mosconi P., Guerra T., Paletta P., D'Ettorre A., Ponzio M., Battaglia M. A., Amato M. P., Bergamaschi R., Capobianco M., Comi G., Gasperini C., Patti F., Pugliatti M., Ulivelli M., Trojano M., Lepore V., Aguglia U., Amato M., Ancona A., Ardito B., Avolio C., Balgera R., Banfi P., Barcella V., Barone P., Bellantonio P., Berardinelli A., Bertora P., Bianchi M., Bramanti P., Brescia Morra V., Brichetto G., Brioschi A., Buccafusca M., Bucello S., Busillo V., Calchetti B., Cantello R., Capone F., Capone L., Cargnelutti D., Carozzi M., Cartechini E., Cavaletti G., Cavalla P., Celani M., Clerici R., Clerico M., Cocco E., Torri Clerici V., Coniglio M., Conte A., Corea F., Cottone S., Crociani P., D'Andrea F., Danni M., De Luca G., de Pascalis D., De Riz M., De Robertis F., De Rosa G., De Stefano N., Della Corte M., Di Sapio A., Docimo R., Falcini M., Falcone N., Fermi S., Ferraro E., Ferro M., Fortunato M., Foschi M., Gajofatto A., Gallo A., Gallo P., Gatto M., Gazzola P., Giordano A., Granella F., Grasso M., Grimaldi L., Iaffaldano P., Immovilli P., Imperiale D., Inglese M., Iodice R., Leva S., Leuzzi V., Lugaresi A., Lus G., Maimone D., Mancinelli L., Maniscalco G., Marfia G., Margari L., Marinelli F., Marini B., Marson A., Mascoli N., Massacesi L., Melani F., Merello M., Fioretti C., Mirabella M., Montepietra S., Nasuelli D., Nicolao P., Pasquali L., Passantino F., Pecori C., Peresson M., Pesci I., Piantadosi C., Piras M., Pizzorno M., Plewnia K., Pozzilli C., Protti A., Quatrale R., Realmuto S., Ribizzi G., Rinalduzzi S., Rini A., Romano S., Filippi M., Ronzoni M., Rossi P., Rovaris M., Salemi G., Santangelo G., Santangelo M., Leone A., Sarchielli P., Sinisi L., Ferraro D., Solaro C., Spitaleri D., Strumia S., Tassinari T., Santuccio G., Tortorella C., Totaro R., Tozzo A., Trivelli G., Turano G., Valentino P., Venturi S., Vianello M., Zaffaroni M., Zarbo R., Mosconi, P, Guerra, T, Paletta, P, D'Ettorre, A, Ponzio, M, Battaglia, M, Amato, M, Bergamaschi, R, Capobianco, M, Comi, G, Gasperini, C, Patti, F, Pugliatti, M, Ulivelli, M, Trojano, M, Lepore, V, Aguglia, U, Ancona, A, Ardito, B, Avolio, C, Balgera, R, Banfi, P, Barcella, V, Barone, P, Bellantonio, P, Berardinelli, A, Bertora, P, Bianchi, M, Bramanti, P, Brescia Morra, V, Brichetto, G, Brioschi, A, Buccafusca, M, Bucello, S, Busillo, V, Calchetti, B, Cantello, R, Capone, F, Capone, L, Cargnelutti, D, Carozzi, M, Cartechini, E, Cavaletti, G, Cavalla, P, Celani, M, Clerici, R, Clerico, M, Cocco, E, Torri Clerici, V, Coniglio, M, Conte, A, Corea, F, Cottone, S, Crociani, P, D'Andrea, F, Danni, M, De Luca, G, de Pascalis, D, De Riz, M, De Robertis, F, De Rosa, G, De Stefano, N, Della Corte, M, Di Sapio, A, Docimo, R, Falcini, M, Falcone, N, Fermi, S, Ferraro, E, Ferro, M, Fortunato, M, Foschi, M, Gajofatto, A, Gallo, A, Gallo, P, Gatto, M, Gazzola, P, Giordano, A, Granella, F, Grasso, M, Grimaldi, L, Iaffaldano, P, Immovilli, P, Imperiale, D, Inglese, M, Iodice, R, Leva, S, Leuzzi, V, Lugaresi, A, Lus, G, Maimone, D, Mancinelli, L, Maniscalco, G, Marfia, G, Margari, L, Marinelli, F, Marini, B, Marson, A, Mascoli, N, Massacesi, L, Melani, F, Merello, M, Fioretti, C, Mirabella, M, Montepietra, S, Nasuelli, D, Nicolao, P, Pasquali, L, Passantino, F, Pecori, C, Peresson, M, Pesci, I, Piantadosi, C, Piras, M, Pizzorno, M, Plewnia, K, Pozzilli, C, Protti, A, Quatrale, R, Realmuto, S, Ribizzi, G, Rinalduzzi, S, Rini, A, Romano, S, Filippi, M, Ronzoni, M, Rossi, P, Rovaris, M, Salemi, G, Santangelo, G, Santangelo, M, Leone, A, Sarchielli, P, Sinisi, L, Ferraro, D, Solaro, C, Spitaleri, D, Strumia, S, Tassinari, T, Santuccio, G, Tortorella, C, Totaro, R, Tozzo, A, Trivelli, G, Turano, G, Valentino, P, Venturi, S, Vianello, M, Zaffaroni, M, Zarbo, R, Mosconi P., Guerra T., Paletta P., D'Ettorre A., Ponzio M., Battaglia M. A., Amato M. P., Bergamaschi R., Capobianco M., Comi G., Gasperini C., Patti F., Pugliatti M., Ulivelli M., Trojano M., Lepore V., Aguglia U., Amato M., Ancona A., Ardito B., Avolio C., Balgera R., Banfi P., Barcella V., Barone P., Bellantonio P., Berardinelli A., Bertora P., Bianchi M., Bramanti P., Brescia Morra V., Brichetto G., Brioschi A., Buccafusca M., Bucello S., Busillo V., Calchetti B., Cantello R., Capone F., Capone L., Cargnelutti D., Carozzi M., Cartechini E., Cavaletti G., Cavalla P., Celani M., Clerici R., Clerico M., Cocco E., Torri Clerici V., Coniglio M., Conte A., Corea F., Cottone S., Crociani P., D'Andrea F., Danni M., De Luca G., de Pascalis D., De Riz M., De Robertis F., De Rosa G., De Stefano N., Della Corte M., Di Sapio A., Docimo R., Falcini M., Falcone N., Fermi S., Ferraro E., Ferro M., Fortunato M., Foschi M., Gajofatto A., Gallo A., Gallo P., Gatto M., Gazzola P., Giordano A., Granella F., Grasso M., Grimaldi L., Iaffaldano P., Immovilli P., Imperiale D., Inglese M., Iodice R., Leva S., Leuzzi V., Lugaresi A., Lus G., Maimone D., Mancinelli L., Maniscalco G., Marfia G., Margari L., Marinelli F., Marini B., Marson A., Mascoli N., Massacesi L., Melani F., Merello M., Fioretti C., Mirabella M., Montepietra S., Nasuelli D., Nicolao P., Pasquali L., Passantino F., Pecori C., Peresson M., Pesci I., Piantadosi C., Piras M., Pizzorno M., Plewnia K., Pozzilli C., Protti A., Quatrale R., Realmuto S., Ribizzi G., Rinalduzzi S., Rini A., Romano S., Filippi M., Ronzoni M., Rossi P., Rovaris M., Salemi G., Santangelo G., Santangelo M., Leone A., Sarchielli P., Sinisi L., Ferraro D., Solaro C., Spitaleri D., Strumia S., Tassinari T., Santuccio G., Tortorella C., Totaro R., Tozzo A., Trivelli G., Turano G., Valentino P., Venturi S., Vianello M., Zaffaroni M., and Zarbo R.
Abstract: Introduction: Over the years, disease registers have been increasingly considered a source of reliable and valuable population studies. However, the validity and reliability of data from registers may be limited by missing data, selection bias or data quality not adequately evaluated or checked. This study reports the analysis of the consistency and completeness of the data in the Italian Multiple Sclerosis and Related Disorders Register. Methods: The Register collects, through a standardized Web-based Application, unique patients. Data are exported bimonthly and evaluated to assess the updating and completeness, and to check the quality and consistency. Eight clinical indicators are evaluated. Results: The Register counts 77,628 patients registered by 126 centres. The number of centres has increased over time, as their capacity to collect patients. The percentages of updated patients (with at least one visit in the last 24 months) have increased from 33% (enrolment period 2000–2015) to 60% (enrolment period 2016–2022). In the cohort of patients registered after 2016, there were ≥ 75% updated patients in 30% of the small centres (33), in 9% of the medium centres (11), and in all the large centres (2). Clinical indicators show significant improvement for the active patients, expanded disability status scale every 6 months or once every 12 months, visits every 6 months, first visit within 1 year and MRI every 12 months. Conclusions: Data from disease registers provide guidance for evidence-based health policies and research, so methods and strategies ensuring their quality and reliability are crucial and have several potential applications.
Published: 2023

3. Data monitoring roadmap. The experience of the Italian Multiple Sclerosis and Related Disorders Register

Author: Mosconi, P., Guerra, T., Paletta, P., D’Ettorre, A., Ponzio, M., Battaglia, M. A., Amato, M. P., Bergamaschi, R., Capobianco, M., Comi, G., Gasperini, C., Patti, F., Pugliatti, M., Ulivelli, M., Trojano, M., Lepore, V., Aguglia, U., Amato, M., Ancona, A., Ardito, B., Avolio, C., Balgera, R., Banfi, P., Barcella, V., Barone, P., Bellantonio, P., Berardinelli, A., Bertora, P., Bianchi, M., Bramanti, P., Brescia Morra, V., Brichetto, G., Brioschi, A., Buccafusca, M., Bucello, S., Busillo, V., Calchetti, B., Cantello, R., Capone, F., Capone, L., Cargnelutti, D., Carozzi, M., Cartechini, E., Cavaletti, G., Cavalla, P., Celani, M., Clerici, R., Clerico, M., Cocco, E., Torri Clerici, V., Coniglio, M., Conte, A., Corea, F., Cottone, S., Crociani, P., D’Andrea, F., Danni, M., De Luca, G., de Pascalis, D., De Riz, M., De Robertis, F., De Rosa, G., De Stefano, N., Della Corte, M., Di Sapio, A., Docimo, R., Falcini, M., Falcone, N., Fermi, S., Ferraro, E., Ferrò, M., Fortunato, M., Foschi, M., Gajofatto, A., Gallo, A., Gallo, P., Gatto, M., Gazzola, P., Giordano, A., Granella, F., Grasso, M., Grimaldi, L., Iaffaldano, P., Immovilli, P., Imperiale, D., Inglese, M., Iodice, R., Leva, S., Leuzzi, V., Lugaresi, A., Lus, G., Maimone, D., Mancinelli, L., Maniscalco, G., Marfia, G., Margari, L., Marinelli, F., Marini, B., Marson, A., Mascoli, N., Massacesi, L., Melani, F., Merello, M., Fioretti, C., Mirabella, Massimiliano, Montepietra, S., Nasuelli, D., Nicolao, P., Pasquali, L., Passantino, F., Pecori, C., Peresson, M., Pesci, I., Piantadosi, C., Piras, M. L., Pizzorno, M., Plewnia, K., Pozzilli, C., Protti, A., Quatrale, R., Realmuto, S., Ribizzi, G., Rinalduzzi, S., Rini, A., Romano, S., Filippi, M., Ronzoni, M., Rossi, P., Rovaris, M., Salemi, G., Santangelo, G., Santangelo, M., Leone, A., Sarchielli, P., Sinisi, L., Ferraro, D., Solaro, C., Spitaleri, D., Strumia, S., Tassinari, T., Santuccio, G., Tortorella, C., Totaro, R., Tozzo, A., Trivelli, G., Turano, G., Valentino, P., Venturi, S., Vianello, M., Zaffaroni, M., Zarbo, R., Mirabella M. (ORCID:0000-0002-7783-114X), Mosconi, P., Guerra, T., Paletta, P., D’Ettorre, A., Ponzio, M., Battaglia, M. A., Amato, M. P., Bergamaschi, R., Capobianco, M., Comi, G., Gasperini, C., Patti, F., Pugliatti, M., Ulivelli, M., Trojano, M., Lepore, V., Aguglia, U., Amato, M., Ancona, A., Ardito, B., Avolio, C., Balgera, R., Banfi, P., Barcella, V., Barone, P., Bellantonio, P., Berardinelli, A., Bertora, P., Bianchi, M., Bramanti, P., Brescia Morra, V., Brichetto, G., Brioschi, A., Buccafusca, M., Bucello, S., Busillo, V., Calchetti, B., Cantello, R., Capone, F., Capone, L., Cargnelutti, D., Carozzi, M., Cartechini, E., Cavaletti, G., Cavalla, P., Celani, M., Clerici, R., Clerico, M., Cocco, E., Torri Clerici, V., Coniglio, M., Conte, A., Corea, F., Cottone, S., Crociani, P., D’Andrea, F., Danni, M., De Luca, G., de Pascalis, D., De Riz, M., De Robertis, F., De Rosa, G., De Stefano, N., Della Corte, M., Di Sapio, A., Docimo, R., Falcini, M., Falcone, N., Fermi, S., Ferraro, E., Ferrò, M., Fortunato, M., Foschi, M., Gajofatto, A., Gallo, A., Gallo, P., Gatto, M., Gazzola, P., Giordano, A., Granella, F., Grasso, M., Grimaldi, L., Iaffaldano, P., Immovilli, P., Imperiale, D., Inglese, M., Iodice, R., Leva, S., Leuzzi, V., Lugaresi, A., Lus, G., Maimone, D., Mancinelli, L., Maniscalco, G., Marfia, G., Margari, L., Marinelli, F., Marini, B., Marson, A., Mascoli, N., Massacesi, L., Melani, F., Merello, M., Fioretti, C., Mirabella, Massimiliano, Montepietra, S., Nasuelli, D., Nicolao, P., Pasquali, L., Passantino, F., Pecori, C., Peresson, M., Pesci, I., Piantadosi, C., Piras, M. L., Pizzorno, M., Plewnia, K., Pozzilli, C., Protti, A., Quatrale, R., Realmuto, S., Ribizzi, G., Rinalduzzi, S., Rini, A., Romano, S., Filippi, M., Ronzoni, M., Rossi, P., Rovaris, M., Salemi, G., Santangelo, G., Santangelo, M., Leone, A., Sarchielli, P., Sinisi, L., Ferraro, D., Solaro, C., Spitaleri, D., Strumia, S., Tassinari, T., Santuccio, G., Tortorella, C., Totaro, R., Tozzo, A., Trivelli, G., Turano, G., Valentino, P., Venturi, S., Vianello, M., Zaffaroni, M., Zarbo, R., and Mirabella M. (ORCID:0000-0002-7783-114X)
Abstract: IntroductionOver the years, disease registers have been increasingly considered a source of reliable and valuable population studies. However, the validity and reliability of data from registers may be limited by missing data, selection bias or data quality not adequately evaluated or checked.This study reports the analysis of the consistency and completeness of the data in the Italian Multiple Sclerosis and Related Disorders Register.MethodsThe Register collects, through a standardized Web-based Application, unique patients.Data are exported bimonthly and evaluated to assess the updating and completeness, and to check the quality and consistency. Eight clinical indicators are evaluated.ResultsThe Register counts 77,628 patients registered by 126 centres. The number of centres has increased over time, as their capacity to collect patients.The percentages of updated patients (with at least one visit in the last 24 months) have increased from 33% (enrolment period 2000-2015) to 60% (enrolment period 2016-2022). In the cohort of patients registered after 2016, there were >= 75% updated patients in 30% of the small centres (33), in 9% of the medium centres (11), and in all the large centres (2).Clinical indicators show significant improvement for the active patients, expanded disability status scale every 6 months or once every 12 months, visits every 6 months, first visit within 1 year and MRI every 12 months.ConclusionsData from disease registers provide guidance for evidence-based health policies and research, so methods and strategies ensuring their quality and reliability are crucial and have several potential applications.
Published: 2023

4. Disease-Modifying Treatments and Time to Loss of Ambulatory Function in Patients with Primary Progressive Multiple Sclerosis

Author: Portaccio, E, Fonderico, M, Iaffaldano, P, Pasto, L, Razzolini, L, Bellinvia, A, De Luca, G, Ragonese, P, Patti, F, Brescia Morra, V, Cocco, E, Sola, P, Inglese, M, Lus, G, Pozzilli, C, Maimone, D, Lugaresi, A, Gazzola, P, Comi, G, Pesci, I, Spitaleri, D, Rezzonico, M, Vianello, M, Avolio, C, Logullo, F, Granella, F, Salvetti, M, Zaffaroni, M, Lucisano, G, Filippi, M, Trojano, M, Amato, M, Cavaletti, G, Portaccio E., Fonderico M., Iaffaldano P., Pasto L., Razzolini L., Bellinvia A., De Luca G., Ragonese P., Patti F., Brescia Morra V., Cocco E., Sola P., Inglese M., Lus G., Pozzilli C., Maimone D., Lugaresi A., Gazzola P., Comi G., Pesci I., Spitaleri D., Rezzonico M., Vianello M., Avolio C., Logullo F. O., Granella F., Salvetti M., Zaffaroni M., Lucisano G., Filippi M., Trojano M., Amato M. P., Cavaletti G., Portaccio, E, Fonderico, M, Iaffaldano, P, Pasto, L, Razzolini, L, Bellinvia, A, De Luca, G, Ragonese, P, Patti, F, Brescia Morra, V, Cocco, E, Sola, P, Inglese, M, Lus, G, Pozzilli, C, Maimone, D, Lugaresi, A, Gazzola, P, Comi, G, Pesci, I, Spitaleri, D, Rezzonico, M, Vianello, M, Avolio, C, Logullo, F, Granella, F, Salvetti, M, Zaffaroni, M, Lucisano, G, Filippi, M, Trojano, M, Amato, M, Cavaletti, G, Portaccio E., Fonderico M., Iaffaldano P., Pasto L., Razzolini L., Bellinvia A., De Luca G., Ragonese P., Patti F., Brescia Morra V., Cocco E., Sola P., Inglese M., Lus G., Pozzilli C., Maimone D., Lugaresi A., Gazzola P., Comi G., Pesci I., Spitaleri D., Rezzonico M., Vianello M., Avolio C., Logullo F. O., Granella F., Salvetti M., Zaffaroni M., Lucisano G., Filippi M., Trojano M., Amato M. P., and Cavaletti G.
Abstract: Importance: Except for ocrelizumab, treatment options in primary progressive multiple sclerosis (PPMS) are lacking. Objective: To investigate the effectiveness of DMTs on the risk of becoming wheelchair dependent in a real-world population of patients with PPMS. Design, Setting, and Participants: This was a multicenter, observational, retrospective, comparative effectiveness research study. Data were extracted on November 28, 2018, from the Italian multiple sclerosis register and analyzed from June to December 2021. Mean study follow-up was 11 years. Included in the study cohort were patients with a diagnosis of PPMS and at least 3 years of Expanded Disability Status Scale (EDSS) evaluations and 3 years of follow-up. Main Outcomes and Measures: The risk of reaching an EDSS score of 7.0 was assessed through multivariable Cox regression models. Exposures: Patients who received DMT before the outcome were considered treated. DMT was assessed as a time-dependent variable and by class of DMT (moderately and highly effective). Results: From a total of 3298 patients with PPMS, 2633 were excluded because they did not meet the entry criteria for the phase 3, multicenter, randomized, parallel-group, double-blind, placebo-controlled study to evaluate the efficacy and safety of ocrelizumab in adults with PPMS (ORATORIO) trial. Among the remaining 665 patients (mean [SD] age, 43.0 [10.7] years; 366 female patients [55.0%]), 409 were further selected for propensity score matching (288 treated and 121 untreated patients). In the matched cohort, during the study follow-up, 37% of patients (152 of 409) reached an EDSS score of 7.0 after a mean (SD) follow-up of 10.6 (5.6) years. A higher EDSS score at baseline (adjusted hazard ratio [aHR], 1.32; 95% CI, 1.13-1.55; P <.001), superimposed relapses (aHR, 2.37; 95% CI, 1.24-4.54; P =.009), and DMT exposure (aHR, 1.75; 95% CI, 1.04-2.94; P =.03) were associated with a higher risk of an EDSS score of 7.0, whereas the interaction term b
Published: 2022

5. Do patients' and referral centers' characteristics influence multiple sclerosis phenotypes? Results from the Italian multiple sclerosis and related disorders register

Author: Bergamaschi, Roberto, Beghi, Ettore, Bosetti, Cristina, Ponzio, Michela, Santucci, Claudia, Lepore, Vito, Mosconi, Paola, Aguglia, U, Amato, M P, Ancona, A L, Ardito, B, Avolio, C, Balgera, R, Banfi, P, Barcella, V, Barone, P, Bellantonio, P, Berardinelli, A, Bergamaschi, R, Bertora, P, Bianchi, M, Bramanti, P, Morra, V Brescia, Brichetto, G, Brioschi, A M, Buccafusca, M, Bucello, S, Busillo, V, Calchetti, B, Cantello, R, Capobianco, M, Capone, F, Capone, L, Cargnelutti, D, Carrozzi, M, Cartechini, E, Cavaletti, G, Cavalla, P, Celani, M G, Clerici, R, Clerico, M, Cocco, E, Confalonieri, P, Coniglio, M G, Conte, A, Corea, F, Cottone, S, Crociani, P, D'Andrea, F, Danni, M C, De Luca, G, de Pascalis, D, De Riz, M, De Robertis, F, De Rosa, G, De Stefano, N, Corte, M Della, Di Sapio, A, Docimo, R, Falcini, M, Falcone, N, Fermi, S, Ferraro, E, Ferrò, M T, Fortunato, M, Foschi, M, Gajofatto, A, Gallo, A, Gallo, P, Gatto, M, Gazzola, P, Giordano, A, Granella, F, Grasso, M F, Grasso, M G, Grimaldi, L M E, Iaffaldano, P, Imperiale, D, Inglese, M, Iodice, R, Leva, S, Luezzi, V, Lugaresi, A, Lus, G, Maimone, D, Mancinelli, L, Maniscalco, G T, Marfia, G A, Marini, B, Marson, A, Mascoli, N, Massacesi, L, Melani, F, Merello, M, Meucci, G, Mirabella, M, Montepietra, S, Nasuelli, D, Nicolao, P, Passantino, F, Patti, F, Peresson, M, Pesci, I, Piantadosi, C, Piras, M L, Pizzorno, M, Plewnia, K, Pozzilli, C, Protti, A, Quatrale, R, Realmuto, S, Ribizzi, G, Rinalduzzi, S, Rini, A, Romano, S, Romeo, M, Ronzoni, M, Rossi, P, Rovaris, M, Salemi, G, Santangelo, G, Santangelo, M, Santuccio, G, Sarchielli, P, Sinisi, L, Sola, P, Solaro, C, Spitaleri, D, Strumia, S, Tassinari, T, Tonietti, S, Tortorella, C, Totaro, R, Tozzo, A, Trivelli, G, Ulivelli, M, Valentino, P, Venturi, S, Vianello, M, Zaffaroni, M, Zarbo, R, Trojano, Maria, Battaglia, Mario Alberto, Capobianco, Marco, Pugliatti, Maura, Ulivelli, Monica, Gasperini, Claudio, Patti, Francesco, Amato, Maria Pia, Comi, Giancarlo, Bergamaschi, R, Beghi, E, Bosetti, C, Ponzio, M, Santucci, C, Lepore, V, Mosconi, P, Aguglia, U, Amato, M, Ancona, A, Ardito, B, Avolio, C, Balgera, R, Banfi, P, Barcella, V, Barone, P, Bellantonio, P, Berardinelli, A, Bertora, P, Bianchi, M, Bramanti, P, Morra, V, Brichetto, G, Brioschi, A, Buccafusca, M, Bucello, S, Busillo, V, Calchetti, B, Cantello, R, Capobianco, M, Capone, F, Capone, L, Cargnelutti, D, Carrozzi, M, Cartechini, E, Cavaletti, G, Cavalla, P, Celani, M, Clerici, R, Clerico, M, Cocco, E, Confalonieri, P, Coniglio, M, Conte, A, Corea, F, Cottone, S, Crociani, P, D'Andrea, F, Danni, M, De Luca, G, de Pascalis, D, De Riz, M, De Robertis, F, De Rosa, G, De Stefano, N, Corte, M, Di Sapio, A, Docimo, R, Falcini, M, Falcone, N, Fermi, S, Ferraro, E, Ferrò, M, Fortunato, M, Foschi, M, Gajofatto, A, Gallo, A, Gallo, P, Gatto, M, Gazzola, P, Giordano, A, Granella, F, Grasso, M, Grimaldi, L, Iaffaldano, P, Imperiale, D, Inglese, M, Iodice, R, Leva, S, Luezzi, V, Lugaresi, A, Lus, G, Maimone, D, Mancinelli, L, Maniscalco, G, Marfia, G, Marini, B, Marson, A, Mascoli, N, Massacesi, L, Melani, F, Merello, M, Meucci, G, Mirabella, M, Montepietra, S, Nasuelli, D, Nicolao, P, Passantino, F, Patti, F, Peresson, M, Pesci, I, Piantadosi, C, Piras, M, Pizzorno, M, Plewnia, K, Pozzilli, C, Protti, A, Quatrale, R, Realmuto, S, Ribizzi, G, Rinalduzzi, S, Rini, A, Romano, S, Romeo, M, Ronzoni, M, Rossi, P, Rovaris, M, Salemi, G, Santangelo, G, Santangelo, M, Santuccio, G, Sarchielli, P, Sinisi, L, Sola, P, Solaro, C, Spitaleri, D, Strumia, S, Tassinari, T, Tonietti, S, Tortorella, C, Totaro, R, Tozzo, A, Trivelli, G, Ulivelli, M, Valentino, P, Venturi, S, Vianello, M, Zaffaroni, M, Zarbo, R, Trojano, M, Battaglia, M, Pugliatti, M, Gasperini, C, Comi, G, Bergamaschi, Roberto, Beghi, Ettore, Bosetti, Cristina, Ponzio, Michela, Santucci, Claudia, Lepore, Vito, Mosconi, Paola, Amato, M P, Ancona, A L, Morra, V Brescia, Brioschi, A M, Celani, M G, Coniglio, M G, Danni, M C, Corte, M Della, Ferrò, M T, Grasso, M F, Grasso, M G, Grimaldi, L M E, Maniscalco, G T, Marfia, G A, Piras, M L, Trojano, Maria, Battaglia, Mario Alberto, Capobianco, Marco, Pugliatti, Maura, Ulivelli, Monica, Gasperini, Claudio, Patti, Francesco, Amato, Maria Pia, and Comi, Giancarlo
Subjects: Multiple Sclerosis, Centers’ characteristics, Italian Multiple Sclerosis Register, Multiple sclerosis phenotypes, Real-world data, Settore MED/42 - Igiene Generale e Applicata, Dermatology, General Medicine, Multiple Sclerosis, Chronic Progressive, Settore MED/26, Settore SECS-S/04 - Demografia, Multiple sclerosis phenotype, Settore MED/01 - Statistica Medica, Psychiatry and Mental health, Multiple Sclerosis, Relapsing-Remitting, Phenotype, Recurrence, Humans, Female, Settore MED/26 - Neurologia, Neurology (clinical), Centers’ characteristic, Referral and Consultation
Abstract: Background Multiple sclerosis (MS) is characterized by phenotypical heterogeneity, partly resulting from demographic and environmental risk factors. Socio-economic factors and the characteristics of local MS facilities might also play a part. Methods This study included patients with a confirmed MS diagnosis enrolled in the Italian MS and Related Disorders Register in 2000–2021. Patients at first visit were classified as having a clinically isolated syndrome (CIS), relapsing–remitting (RR), primary progressive (PP), progressive-relapsing (PR), or secondary progressive MS (SP). Demographic and clinical characteristics were analyzed, with centers’ characteristics, geographic macro-areas, and Deprivation Index. We computed the odds ratios (OR) for CIS, PP/PR, and SP phenotypes, compared to the RR, using multivariate, multinomial, mixed effects logistic regression models. Results In all 35,243 patients from 106 centers were included. The OR of presenting more advanced MS phenotypes than the RR phenotype at first visit significantly diminished in relation to calendar period. Females were at a significantly lower risk of a PP/PR or SP phenotype. Older age was associated with CIS, PP/PR, and SP. The risk of a longer interval between disease onset and first visit was lower for the CIS phenotype, but higher for PP/PR and SP. The probability of SP at first visit was greater in the South of Italy. Discussion Differences in the phenotype of MS patients first seen in Italian centers can be only partly explained by differences in the centers’ characteristics. The demographic and socio-economic characteristics of MS patients seem to be the main determinants of the phenotypes at first referral.
Published: 2022

6. Detection of disability worsening in relapsing-remitting multiple sclerosis patients: a real-world roving Expanded Disability Status Scale reference analysis from the Italian Multiple Sclerosis Register

Author: Lepore, V, Bosetti, C, Santucci, C, Iaffaldano, P, Trojano, M, Mosconi, P, Totaro, R, Coniglio, M, Bossio, R, Valentino, P, Gatto, M, Paolicelli, D, Ardito, B, Barcella, V, Capone, L, Nicolao, P, Lugaresi, A, Rini, A, Bianchi, M, Plasmati, I, Cocco, E, Docimo, R, De Luca, G, Mondino, F, Di Sapio, A, Clerici, R, Mascoli, N, Ferro, M, Chisari, C, Maimone, D, Strumia, S, Pugliatti, M, Cargnelutti, D, Caniatti, L, Avolio, C, Crociani, P, Amato, M, Massacesi, L, Malagu, S, Ribizzi, G, Inglese, M, Venturi, S, Gazzola, P, Pizio, N, Brichetto, G, Plewnia, K, Bellantonio, P, Balgera, R, De Robertis, F, Fermi, S, Fausto, F, Mazzoni, M, Meucci, G, Cartechini, E, Cavaletti, G, Buccafusca, M, Bramanti, P, Romeo, M, Rovaris, M, Ronzoni, M, Confalonieri, P, Chiveri, L, Bertora, P, Tonietti, S, De Riz, M, Protti, A, Sola, P, Maremmani, C, Lus, G, Gallo, A, Maniscalco, G, Morra, V, Cacchio, G, Iodice, R, Ragno, M, Sinisi, L, Cantello, R, Piras, M, Salemi, G, Cottone, S, Grimaldi, L, Corea, F, Santangelo, G, Immovili, P, Gallo, P, D'Andrea, F, Frittelli, C, Pasquali, L, Falcini, M, Granella, F, Pesci, I, Ancona, A, Bergamaschi, R, Giordano, A, Di Napoli, M, Romano, S, Pozzilli, C, Mirabella, M, Conte, A, Galgani, S, Peresson, M, Grasso, M, Ferraro, E, Capone, F, Marfia, G, de Pascalis, D, Piantadosi, C, Valeriani, M, Busillo, V, Barone, P, De Stefano, N, Ulivelli, M, Santuccio, G, Parodi, S, Bucello, S, Traccis, S, Zarbo, R, Tassinari, T, Bandini, F, Cavalla, P, Clerico, M, De Rosa, G, Bertolotto, A, Imperiale, D, Sarchielli, P, Celani, M, Vianello, M, Marini, B, Fortunato, M, Zaffaroni, M, Nasuelli, D, Banfi, P, Brioschi, A, Solaro, C, Quatrale, R, Rossi, P, Gajofatto, A, Battaglia, M, Capobianco, M, Patti, F, Comi, G, Lepore V., Bosetti C., Santucci C., Iaffaldano P., Trojano M., Mosconi P., Totaro R., Coniglio M. G., Bossio R. B., Valentino P., Gatto M., Paolicelli D., Ardito B., Barcella V., Capone L., Nicolao P., Lugaresi A., Rini A., Bianchi M., Plasmati I., Cocco E., Docimo R., De Luca G., Mondino F., Di Sapio A., Clerici R., Mascoli N., Ferro M. T., Chisari C. G., Maimone D., Strumia S., Pugliatti M., Cargnelutti D., Caniatti L. M., Avolio C., Crociani P., Amato M. P., Massacesi L., Malagu S., Ribizzi G., Inglese M., Venturi S., Gazzola P., Pizio N. R., Brichetto G., Plewnia K., Bellantonio P., Balgera R., De Robertis F., Fermi S., Fausto F., Mazzoni M., Meucci G., Cartechini E., Cavaletti G., Buccafusca M., Bramanti P., Romeo M., Rovaris M., Ronzoni M., Confalonieri P., Chiveri L., Bertora P., Tonietti S., De Riz M., Protti A., Sola P., Maremmani C., Lus G., Gallo A., Maniscalco G. T., Morra V. B., Cacchio G., Iodice R., Ragno M., Sinisi L., Cantello R., Piras M. L., Salemi G., Cottone S., Grimaldi L. M. E., Corea F., Santangelo G., Immovili P., Gallo P., D'Andrea F., Frittelli C., Pasquali L., Falcini M., Granella F., Pesci I., Ancona A. L., Bergamaschi R., Giordano A., Di Napoli M., Romano S., Pozzilli C., Mirabella M., Conte A., Galgani S., Peresson M., Grasso M. G., Ferraro E., Capone F., Marfia G. A., de Pascalis D., Piantadosi C., Valeriani M., Busillo V., Barone P., De Stefano N., Ulivelli M., Santuccio G., Parodi S., Bucello S., Traccis S., Zarbo R., Tassinari T., Bandini F., Cavalla P., Clerico M., De Rosa G., Bertolotto A., Imperiale D., Sarchielli P., Celani M. G., Vianello M., Marini B., Fortunato M., Zaffaroni M., Nasuelli D., Banfi P., Brioschi A. M., Solaro C., Quatrale R., Rossi P., Gajofatto A., Battaglia M. A., Capobianco M., Patti F., Comi G., Lepore, V, Bosetti, C, Santucci, C, Iaffaldano, P, Trojano, M, Mosconi, P, Totaro, R, Coniglio, M, Bossio, R, Valentino, P, Gatto, M, Paolicelli, D, Ardito, B, Barcella, V, Capone, L, Nicolao, P, Lugaresi, A, Rini, A, Bianchi, M, Plasmati, I, Cocco, E, Docimo, R, De Luca, G, Mondino, F, Di Sapio, A, Clerici, R, Mascoli, N, Ferro, M, Chisari, C, Maimone, D, Strumia, S, Pugliatti, M, Cargnelutti, D, Caniatti, L, Avolio, C, Crociani, P, Amato, M, Massacesi, L, Malagu, S, Ribizzi, G, Inglese, M, Venturi, S, Gazzola, P, Pizio, N, Brichetto, G, Plewnia, K, Bellantonio, P, Balgera, R, De Robertis, F, Fermi, S, Fausto, F, Mazzoni, M, Meucci, G, Cartechini, E, Cavaletti, G, Buccafusca, M, Bramanti, P, Romeo, M, Rovaris, M, Ronzoni, M, Confalonieri, P, Chiveri, L, Bertora, P, Tonietti, S, De Riz, M, Protti, A, Sola, P, Maremmani, C, Lus, G, Gallo, A, Maniscalco, G, Morra, V, Cacchio, G, Iodice, R, Ragno, M, Sinisi, L, Cantello, R, Piras, M, Salemi, G, Cottone, S, Grimaldi, L, Corea, F, Santangelo, G, Immovili, P, Gallo, P, D'Andrea, F, Frittelli, C, Pasquali, L, Falcini, M, Granella, F, Pesci, I, Ancona, A, Bergamaschi, R, Giordano, A, Di Napoli, M, Romano, S, Pozzilli, C, Mirabella, M, Conte, A, Galgani, S, Peresson, M, Grasso, M, Ferraro, E, Capone, F, Marfia, G, de Pascalis, D, Piantadosi, C, Valeriani, M, Busillo, V, Barone, P, De Stefano, N, Ulivelli, M, Santuccio, G, Parodi, S, Bucello, S, Traccis, S, Zarbo, R, Tassinari, T, Bandini, F, Cavalla, P, Clerico, M, De Rosa, G, Bertolotto, A, Imperiale, D, Sarchielli, P, Celani, M, Vianello, M, Marini, B, Fortunato, M, Zaffaroni, M, Nasuelli, D, Banfi, P, Brioschi, A, Solaro, C, Quatrale, R, Rossi, P, Gajofatto, A, Battaglia, M, Capobianco, M, Patti, F, Comi, G, Lepore V., Bosetti C., Santucci C., Iaffaldano P., Trojano M., Mosconi P., Totaro R., Coniglio M. G., Bossio R. B., Valentino P., Gatto M., Paolicelli D., Ardito B., Barcella V., Capone L., Nicolao P., Lugaresi A., Rini A., Bianchi M., Plasmati I., Cocco E., Docimo R., De Luca G., Mondino F., Di Sapio A., Clerici R., Mascoli N., Ferro M. T., Chisari C. G., Maimone D., Strumia S., Pugliatti M., Cargnelutti D., Caniatti L. M., Avolio C., Crociani P., Amato M. P., Massacesi L., Malagu S., Ribizzi G., Inglese M., Venturi S., Gazzola P., Pizio N. R., Brichetto G., Plewnia K., Bellantonio P., Balgera R., De Robertis F., Fermi S., Fausto F., Mazzoni M., Meucci G., Cartechini E., Cavaletti G., Buccafusca M., Bramanti P., Romeo M., Rovaris M., Ronzoni M., Confalonieri P., Chiveri L., Bertora P., Tonietti S., De Riz M., Protti A., Sola P., Maremmani C., Lus G., Gallo A., Maniscalco G. T., Morra V. B., Cacchio G., Iodice R., Ragno M., Sinisi L., Cantello R., Piras M. L., Salemi G., Cottone S., Grimaldi L. M. E., Corea F., Santangelo G., Immovili P., Gallo P., D'Andrea F., Frittelli C., Pasquali L., Falcini M., Granella F., Pesci I., Ancona A. L., Bergamaschi R., Giordano A., Di Napoli M., Romano S., Pozzilli C., Mirabella M., Conte A., Galgani S., Peresson M., Grasso M. G., Ferraro E., Capone F., Marfia G. A., de Pascalis D., Piantadosi C., Valeriani M., Busillo V., Barone P., De Stefano N., Ulivelli M., Santuccio G., Parodi S., Bucello S., Traccis S., Zarbo R., Tassinari T., Bandini F., Cavalla P., Clerico M., De Rosa G., Bertolotto A., Imperiale D., Sarchielli P., Celani M. G., Vianello M., Marini B., Fortunato M., Zaffaroni M., Nasuelli D., Banfi P., Brioschi A. M., Solaro C., Quatrale R., Rossi P., Gajofatto A., Battaglia M. A., Capobianco M., Patti F., and Comi G.
Abstract: Background and purpose: In relapsing-remitting multiple sclerosis patients (RRMS) disability progressively accumulates over time. To compare the cumulative probability of 6-month confirmed disability-worsening events using a fixed baseline or a roving Expanded Disability Status Scale (EDSS) reference, in a real-world setting. Methods: A cohort of 7964 RRMS patients followed for 2 or more years, with EDSS scores recorded every 6 months, was selected from the Italian Multiple Sclerosis Register. The overall probability of confirmed disability-worsening events and of confirmed disability-worsening events unrelated to relapse was evaluated using as reference a fixed baseline EDSS score or a roving EDSS score in which the increase had to be separated from the last EDSS assessment by at least 6 or 12 months. Results: Using a fixed baseline EDSS reference, the cumulative probability of 6-year overall confirmed disability-worsening events was 33.2%, and that of events unrelated to relapse was 10.9% (33% of overall confirmed disability-worsening events). Using a roving EDSS, the proportions were respectively 35.2% and 21.3% (61% of overall confirmed disability-worsening events). Conclusions: In a real-world setting, roving EDSS reference scores appear to be more sensitive for detecting confirmed disability-worsening events unrelated to relapse in RRMS patients.
Published: 2021

7. Real world comparison of teriflunomide and dimethyl fumarate in naïve relapsing multiple sclerosis patients: Evidence from the Italian MS register

Author: Zanghi, A., Avolio, C., Amato, M. P., Filippi, M., Trojano, M., Patti, F., Amico, E. D., Zanghi, A., Avolio, C., Amato, M. P., Filippi, M., Trojano, M., Patti, F., and Amico, E. D.
Subjects: Multiple Sclerosis, Efficacy, Toluidines, Dimethyl Fumarate, Hydroxybutyrates, General Medicine, Discontinuation, Dimethyl fumarate, Multiple Sclerosis, Relapsing-Remitting, Neurology, Recurrence, Crotonates, Teriflunomide, Nitriles, Humans, Neurology (clinical), Immunosuppressive Agents
Abstract: Background: Teriflunomide (TERI) and dimethyl fumarate (DMF) are licensed as first-line disease-modifying treatments (DMTs) for relapsing remitting Multiple Sclerosis (RRMS) and are largely replacing injectable DMTs. Methods: All RRMS patients starting TERI or DMF between January 1, 2013, and December 31, 2017, were included in the analysis. Time to first relapse, time to confirmed disability progression (CDP), and time to DMT discontinuation have been investigated. Propensity score with inverse probability treatment weighting (IPTW-PS) was used to adjust comparisons for baseline confounders. The aim of the study was to compare the effectiveness, and rate of discontinuation of TERI and DMF as first therapeutic choice in the Italian MS register. Results: A total of 683 patients were considered for the analyses, 185 on TERI and 498 on DMF. Patients on TERI had higher number of relapses (2.3 ± 1.4 vs 1.9 ± 1.1, p=.033) and higher baseline disability level assessed by Expanded Disability Status Scale (EDSS) (2.0, interquartile range-IQR 1.0–3.0 vs 1.5, IQR 1.0–2.0, p=.013). IPTW adjusted Cox models did not reveal any difference between the investigated DMTs for the investigated outcomes. Conclusions: TERI and DMF have similar effectiveness and rate of discontinuation when employed as first therapeutic choice in RRMS patients.
Published: 2021

8. Do patients' and referral centers' characteristics influence multiple sclerosis phenotypes? Results from the Italian multiple sclerosis and related disorders register

Author: Bergamaschi, R, Beghi, E, Bosetti, C, Ponzio, M, Santucci, C, Lepore, V, Mosconi, P, Aguglia, U, Amato, M, Ancona, A, Ardito, B, Avolio, C, Balgera, R, Banfi, P, Barcella, V, Barone, P, Bellantonio, P, Berardinelli, A, Bertora, P, Bianchi, M, Bramanti, P, Morra, V, Brichetto, G, Brioschi, A, Buccafusca, M, Bucello, S, Busillo, V, Calchetti, B, Cantello, R, Capobianco, M, Capone, F, Capone, L, Cargnelutti, D, Carrozzi, M, Cartechini, E, Cavaletti, G, Cavalla, P, Celani, M, Clerici, R, Clerico, M, Cocco, E, Confalonieri, P, Coniglio, M, Conte, A, Corea, F, Cottone, S, Crociani, P, D'Andrea, F, Danni, M, De Luca, G, de Pascalis, D, De Riz, M, De Robertis, F, De Rosa, G, De Stefano, N, Corte, M, Di Sapio, A, Docimo, R, Falcini, M, Falcone, N, Fermi, S, Ferraro, E, Ferrò, M, Fortunato, M, Foschi, M, Gajofatto, A, Gallo, A, Gallo, P, Gatto, M, Gazzola, P, Giordano, A, Granella, F, Grasso, M, Grimaldi, L, Iaffaldano, P, Imperiale, D, Inglese, M, Iodice, R, Leva, S, Luezzi, V, Lugaresi, A, Lus, G, Maimone, D, Mancinelli, L, Maniscalco, G, Marfia, G, Marini, B, Marson, A, Mascoli, N, Massacesi, L, Melani, F, Merello, M, Meucci, G, Mirabella, M, Montepietra, S, Nasuelli, D, Nicolao, P, Passantino, F, Patti, F, Peresson, M, Pesci, I, Piantadosi, C, Piras, M, Pizzorno, M, Plewnia, K, Pozzilli, C, Protti, A, Quatrale, R, Realmuto, S, Ribizzi, G, Rinalduzzi, S, Rini, A, Romano, S, Romeo, M, Ronzoni, M, Rossi, P, Rovaris, M, Salemi, G, Santangelo, G, Santangelo, M, Santuccio, G, Sarchielli, P, Sinisi, L, Sola, P, Solaro, C, Spitaleri, D, Strumia, S, Tassinari, T, Tonietti, S, Tortorella, C, Totaro, R, Tozzo, A, Trivelli, G, Ulivelli, M, Valentino, P, Venturi, S, Vianello, M, Zaffaroni, M, Zarbo, R, Trojano, M, Battaglia, M, Pugliatti, M, Gasperini, C, Comi, G, Bergamaschi, Roberto, Beghi, Ettore, Bosetti, Cristina, Ponzio, Michela, Santucci, Claudia, Lepore, Vito, Mosconi, Paola, Amato, M P, Ancona, A L, Morra, V Brescia, Brioschi, A M, Celani, M G, Coniglio, M G, Danni, M C, Corte, M Della, Ferrò, M T, Grasso, M F, Grasso, M G, Grimaldi, L M E, Maniscalco, G T, Marfia, G A, Piras, M L, Trojano, Maria, Battaglia, Mario Alberto, Capobianco, Marco, Pugliatti, Maura, Ulivelli, Monica, Gasperini, Claudio, Patti, Francesco, Amato, Maria Pia, Comi, Giancarlo, Bergamaschi, R, Beghi, E, Bosetti, C, Ponzio, M, Santucci, C, Lepore, V, Mosconi, P, Aguglia, U, Amato, M, Ancona, A, Ardito, B, Avolio, C, Balgera, R, Banfi, P, Barcella, V, Barone, P, Bellantonio, P, Berardinelli, A, Bertora, P, Bianchi, M, Bramanti, P, Morra, V, Brichetto, G, Brioschi, A, Buccafusca, M, Bucello, S, Busillo, V, Calchetti, B, Cantello, R, Capobianco, M, Capone, F, Capone, L, Cargnelutti, D, Carrozzi, M, Cartechini, E, Cavaletti, G, Cavalla, P, Celani, M, Clerici, R, Clerico, M, Cocco, E, Confalonieri, P, Coniglio, M, Conte, A, Corea, F, Cottone, S, Crociani, P, D'Andrea, F, Danni, M, De Luca, G, de Pascalis, D, De Riz, M, De Robertis, F, De Rosa, G, De Stefano, N, Corte, M, Di Sapio, A, Docimo, R, Falcini, M, Falcone, N, Fermi, S, Ferraro, E, Ferrò, M, Fortunato, M, Foschi, M, Gajofatto, A, Gallo, A, Gallo, P, Gatto, M, Gazzola, P, Giordano, A, Granella, F, Grasso, M, Grimaldi, L, Iaffaldano, P, Imperiale, D, Inglese, M, Iodice, R, Leva, S, Luezzi, V, Lugaresi, A, Lus, G, Maimone, D, Mancinelli, L, Maniscalco, G, Marfia, G, Marini, B, Marson, A, Mascoli, N, Massacesi, L, Melani, F, Merello, M, Meucci, G, Mirabella, M, Montepietra, S, Nasuelli, D, Nicolao, P, Passantino, F, Patti, F, Peresson, M, Pesci, I, Piantadosi, C, Piras, M, Pizzorno, M, Plewnia, K, Pozzilli, C, Protti, A, Quatrale, R, Realmuto, S, Ribizzi, G, Rinalduzzi, S, Rini, A, Romano, S, Romeo, M, Ronzoni, M, Rossi, P, Rovaris, M, Salemi, G, Santangelo, G, Santangelo, M, Santuccio, G, Sarchielli, P, Sinisi, L, Sola, P, Solaro, C, Spitaleri, D, Strumia, S, Tassinari, T, Tonietti, S, Tortorella, C, Totaro, R, Tozzo, A, Trivelli, G, Ulivelli, M, Valentino, P, Venturi, S, Vianello, M, Zaffaroni, M, Zarbo, R, Trojano, M, Battaglia, M, Pugliatti, M, Gasperini, C, Comi, G, Bergamaschi, Roberto, Beghi, Ettore, Bosetti, Cristina, Ponzio, Michela, Santucci, Claudia, Lepore, Vito, Mosconi, Paola, Amato, M P, Ancona, A L, Morra, V Brescia, Brioschi, A M, Celani, M G, Coniglio, M G, Danni, M C, Corte, M Della, Ferrò, M T, Grasso, M F, Grasso, M G, Grimaldi, L M E, Maniscalco, G T, Marfia, G A, Piras, M L, Trojano, Maria, Battaglia, Mario Alberto, Capobianco, Marco, Pugliatti, Maura, Ulivelli, Monica, Gasperini, Claudio, Patti, Francesco, Amato, Maria Pia, and Comi, Giancarlo
Abstract: Background: Multiple sclerosis (MS) is characterized by phenotypical heterogeneity, partly resulting from demographic and environmental risk factors. Socio-economic factors and the characteristics of local MS facilities might also play a part. Methods: This study included patients with a confirmed MS diagnosis enrolled in the Italian MS and Related Disorders Register in 2000–2021. Patients at first visit were classified as having a clinically isolated syndrome (CIS), relapsing–remitting (RR), primary progressive (PP), progressive-relapsing (PR), or secondary progressive MS (SP). Demographic and clinical characteristics were analyzed, with centers’ characteristics, geographic macro-areas, and Deprivation Index. We computed the odds ratios (OR) for CIS, PP/PR, and SP phenotypes, compared to the RR, using multivariate, multinomial, mixed effects logistic regression models. Results: In all 35,243 patients from 106 centers were included. The OR of presenting more advanced MS phenotypes than the RR phenotype at first visit significantly diminished in relation to calendar period. Females were at a significantly lower risk of a PP/PR or SP phenotype. Older age was associated with CIS, PP/PR, and SP. The risk of a longer interval between disease onset and first visit was lower for the CIS phenotype, but higher for PP/PR and SP. The probability of SP at first visit was greater in the South of Italy. Discussion: Differences in the phenotype of MS patients first seen in Italian centers can be only partly explained by differences in the centers’ characteristics. The demographic and socio-economic characteristics of MS patients seem to be the main determinants of the phenotypes at first referral.
Published: 2022

9. The Italian multiple sclerosis register

Author: Trojano, M, Bergamaschi, R, Amato, M, Comi, G, Ghezzi, A, Lepore, V, Marrosu, M, Mosconi, P, Patti, F, Ponzio, M, Zaratin, P, Battaglia, M, Acquistapace, D, Aguglia, U, Annunziata, P, Ardito, B, Avolio, C, Balgera, R, Bandini, F, Banfi, P, Barone, P, Bellantonio, P, Bertolotto, A, Bertora, P, Bombardi, R, Bosco Zimatore, G, Bossio, R, Bramanti, P, Brescia Morra, V, Brioschi, A, Bruzzone, M, Buccafusca, M, Busillo, V, Caneve, G, Caniatti, L, Capone, L, Capone, F, Cappellani, A, Cargnelutti, D, Cavaletti, G, Cavalla, P, Celani, M, Centonze, D, Chiveri, L, Clerici, R, Clerico, M, Cocco, E, Comi, C, Coniglio, M, Cordera, S, Corea, F, Cortese, A, Costantino, G, Cottone, S, Crociani, P, D’Andrea, F, Danni, M, De Luca, G, de Pascalis, D, De Robertis, F, De Stefano, N, Di Battista, G, Di Napoli, M, Falcini, M, Fausto, F, Ferrò, M, Florio, C, Fortunato, M, Frittelli, C, Galgani, S, Gallo, P, Gatto, M, Gazzola, P, Geda, C, Giordano, A, Granella, F, Grasso, M, Grimaldi, L, Imperiale, D, Lo Russo, L, Logullo, F, Lugaresi, A, Lus, G, Maccarrone, G, Maimone, D, Malagù, S, Marconi, R, Maritato, P, Massacesi, L, Mazzoni, M, Meucci, G, Mirabella, M, Montepietra, S, Nasuelli, D, Neri, W, Orefice, G, Parodi, S, Pasquali, L, Passarella, B, Peresson, M, Perla, F, Pesci, I, Piantadosi, C, Piras, M, Pizio, N, Pozzilli, C, Protti, A, Pugliatti, M, Quatrale, R, Ragno, M, Rezzonico, M, Ribizzi, G, Riva, M, Ronzoni, M, Rosso, M, Rottoli, M, Rovaris, M, Salemi, G, Salvetti, M, Santangelo, M, Santangelo, G, Santuccio, G, Sarchielli, P, Scarpini, E, Sechi, G, Severi, S, Sinisi, L, Sola, P, Spitaleri, D, Tassinari, T, Tedeschi, G, Tonietti, S, Torri Clerici, V, Totaro, R, Traccis, S, Turla, M, Uccelli, A, Ulivelli, M, Valentino, P, Valeriani, M, Venturi, S, Vianello, M, Zaffaroni, M, Trojano, Maria, Bergamaschi, Roberto, Amato, Maria Pia, Comi, Giancarlo, Ghezzi, Angelo, Lepore, Vito, Marrosu, Maria Giovanna, Mosconi, Paola, Patti, Francesco, Ponzio, Michela, Zaratin, Paola, Battaglia, Mario Alberto, Acquistapace, D., Aguglia, U., Amato, M. P., Annunziata, P., Ardito, B., Avolio, C., Balgera, R., Bandini, F., Banfi, P., Barone, P., Bellantonio, P., Bergamaschi, R., Bertolotto, A., Bertora, P., Bombardi, R., Bosco Zimatore, G., Bossio, R. B., Bramanti, P., Brescia Morra, V., Brioschi, A. M., Bruzzone, M., Buccafusca, M., Busillo, V., Caneve, G., Caniatti, L. M., Capone, L., Capone, F., Cappellani, A., Cargnelutti, D., Cavaletti, G., Cavalla, P., Celani, M. G., Centonze, D., Chiveri, L., Clerici, R., Clerico, M., Cocco, E., Comi, G., Comi, C., Coniglio, M. G., Cordera, S., Corea, F., Cortese, A., Costantino, G., Cottone, S., Crociani, P., D’Andrea, F., Danni, M. C., De Luca, G., de Pascalis, D., De Robertis, F., De Stefano, N., Di Battista, G., Di Napoli, M., Falcini, M., Fausto, F., Ferrò, M. T., Florio, C., Fortunato, M., Frittelli, C., Galgani, S., Gallo, P., Gatto, M., Gazzola, P., Geda, C., Giordano, A., Granella, F., Grasso, M. G., Grimaldi, L. M. E., Imperiale, D., Lo Russo, L., Logullo, F. O., Lugaresi, A., Lus, G., Maccarrone, G., Maimone, D., Malagù, S., Marconi, R., Maritato, P., Massacesi, L., Mazzoni, M., Meucci, G., Mirabella, M., Montepietra, S., Nasuelli, D., Neri, W., Orefice, G., Parodi, S., Pasquali, L., Passarella, B., Patti, F., Peresson, M., Perla, F., Pesci, I., Piantadosi, C., Piras, M. L., Pizio, N. R., Pozzilli, C., Protti, A., Pugliatti, M., Quatrale, R., Ragno, M., Rezzonico, M., Ribizzi, G., Riva, M., Ronzoni, M., Rosso, M. G., Rottoli, M., Rovaris, M., Salemi, G., Salvetti, M., Santangelo, M., Santangelo, G., Santuccio, G., Sarchielli, P., Scarpini, E., Sechi, G. P., Severi, S., Sinisi, L., Sola, P., Spitaleri, D., Tassinari, T., Tedeschi, G., Tonietti, S., Torri Clerici, V., Totaro, R., Traccis, S., Trojano, M., Turla, M., Uccelli, A., Ulivelli, M., Valentino, P., Valeriani, M., Venturi, S., Vianello, M., Zaffaroni, M., Trojano, M, Bergamaschi, R, Amato, M, Comi, G, Ghezzi, A, Lepore, V, Marrosu, M, Mosconi, P, Patti, F, Ponzio, M, Zaratin, P, Battaglia, M, Acquistapace, D, Aguglia, U, Annunziata, P, Ardito, B, Avolio, C, Balgera, R, Bandini, F, Banfi, P, Barone, P, Bellantonio, P, Bertolotto, A, Bertora, P, Bombardi, R, Bosco Zimatore, G, Bossio, R, Bramanti, P, Brescia Morra, V, Brioschi, A, Bruzzone, M, Buccafusca, M, Busillo, V, Caneve, G, Caniatti, L, Capone, L, Capone, F, Cappellani, A, Cargnelutti, D, Cavaletti, G, Cavalla, P, Celani, M, Centonze, D, Chiveri, L, Clerici, R, Clerico, M, Cocco, E, Comi, C, Coniglio, M, Cordera, S, Corea, F, Cortese, A, Costantino, G, Cottone, S, Crociani, P, D’Andrea, F, Danni, M, De Luca, G, de Pascalis, D, De Robertis, F, De Stefano, N, Di Battista, G, Di Napoli, M, Falcini, M, Fausto, F, Ferrò, M, Florio, C, Fortunato, M, Frittelli, C, Galgani, S, Gallo, P, Gatto, M, Gazzola, P, Geda, C, Giordano, A, Granella, F, Grasso, M, Grimaldi, L, Imperiale, D, Lo Russo, L, Logullo, F, Lugaresi, A, Lus, G, Maccarrone, G, Maimone, D, Malagù, S, Marconi, R, Maritato, P, Massacesi, L, Mazzoni, M, Meucci, G, Mirabella, M, Montepietra, S, Nasuelli, D, Neri, W, Orefice, G, Parodi, S, Pasquali, L, Passarella, B, Peresson, M, Perla, F, Pesci, I, Piantadosi, C, Piras, M, Pizio, N, Pozzilli, C, Protti, A, Pugliatti, M, Quatrale, R, Ragno, M, Rezzonico, M, Ribizzi, G, Riva, M, Ronzoni, M, Rosso, M, Rottoli, M, Rovaris, M, Salemi, G, Salvetti, M, Santangelo, M, Santangelo, G, Santuccio, G, Sarchielli, P, Scarpini, E, Sechi, G, Severi, S, Sinisi, L, Sola, P, Spitaleri, D, Tassinari, T, Tedeschi, G, Tonietti, S, Torri Clerici, V, Totaro, R, Traccis, S, Turla, M, Uccelli, A, Ulivelli, M, Valentino, P, Valeriani, M, Venturi, S, Vianello, M, Zaffaroni, M, Trojano, Maria, Bergamaschi, Roberto, Amato, Maria Pia, Comi, Giancarlo, Ghezzi, Angelo, Lepore, Vito, Marrosu, Maria Giovanna, Mosconi, Paola, Patti, Francesco, Ponzio, Michela, Zaratin, Paola, Battaglia, Mario Alberto, Acquistapace, D., Aguglia, U., Amato, M. P., Annunziata, P., Ardito, B., Avolio, C., Balgera, R., Bandini, F., Banfi, P., Barone, P., Bellantonio, P., Bergamaschi, R., Bertolotto, A., Bertora, P., Bombardi, R., Bosco Zimatore, G., Bossio, R. B., Bramanti, P., Brescia Morra, V., Brioschi, A. M., Bruzzone, M., Buccafusca, M., Busillo, V., Caneve, G., Caniatti, L. M., Capone, L., Capone, F., Cappellani, A., Cargnelutti, D., Cavaletti, G., Cavalla, P., Celani, M. G., Centonze, D., Chiveri, L., Clerici, R., Clerico, M., Cocco, E., Comi, G., Comi, C., Coniglio, M. G., Cordera, S., Corea, F., Cortese, A., Costantino, G., Cottone, S., Crociani, P., D’Andrea, F., Danni, M. C., De Luca, G., de Pascalis, D., De Robertis, F., De Stefano, N., Di Battista, G., Di Napoli, M., Falcini, M., Fausto, F., Ferrò, M. T., Florio, C., Fortunato, M., Frittelli, C., Galgani, S., Gallo, P., Gatto, M., Gazzola, P., Geda, C., Giordano, A., Granella, F., Grasso, M. G., Grimaldi, L. M. E., Imperiale, D., Lo Russo, L., Logullo, F. O., Lugaresi, A., Lus, G., Maccarrone, G., Maimone, D., Malagù, S., Marconi, R., Maritato, P., Massacesi, L., Mazzoni, M., Meucci, G., Mirabella, M., Montepietra, S., Nasuelli, D., Neri, W., Orefice, G., Parodi, S., Pasquali, L., Passarella, B., Patti, F., Peresson, M., Perla, F., Pesci, I., Piantadosi, C., Piras, M. L., Pizio, N. R., Pozzilli, C., Protti, A., Pugliatti, M., Quatrale, R., Ragno, M., Rezzonico, M., Ribizzi, G., Riva, M., Ronzoni, M., Rosso, M. G., Rottoli, M., Rovaris, M., Salemi, G., Salvetti, M., Santangelo, M., Santangelo, G., Santuccio, G., Sarchielli, P., Scarpini, E., Sechi, G. P., Severi, S., Sinisi, L., Sola, P., Spitaleri, D., Tassinari, T., Tedeschi, G., Tonietti, S., Torri Clerici, V., Totaro, R., Traccis, S., Trojano, M., Turla, M., Uccelli, A., Ulivelli, M., Valentino, P., Valeriani, M., Venturi, S., Vianello, M., and Zaffaroni, M.
Abstract: The past decade has seen extraordinary increase in worldwide availability of and access to several large multiple sclerosis (MS) databases and registries. MS registries represent powerful tools to provide meaningful information on the burden, natural history, and long-term safety and effectiveness of treatments. Moreover, patients, physicians, industry, and policy makers have an active interest in real-world observational studies based on register data, as they have the potential to answer the questions that are most relevant to daily treatment decision-making. In 2014, the Italian MS Foundation, in collaboration with the Italian MS clinical centers, promoted and funded the creation of the Italian MS Register, a project in continuity with the existing Italian MS Database Network set up from 2001. Main objective of the Italian MS Register is to create an organized multicenter structure to collect data of all MS patients for better defining the disease epidemiology, improving quality of care, and promoting research projects in high-priority areas. The aim of this article is to present the current framework and network of the Italian MS register, including the methodology used to improve the quality of data collection and to facilitate the exchange of data and the collaboration among national and international groups.
Published: 2019

10. Detection of disability worsening in relapsing-remitting multiple sclerosis patients: a real-world roving Expanded Disability Status Scale reference analysis from the Italian Multiple Sclerosis Register

Author: Lepore, V., Bosetti, C., Santucci, C., Iaffaldano, P., Trojano, M., Mosconi, P., Totaro, R., Coniglio, M. G., Bossio, R. B., Valentino, P., Gatto, M., Paolicelli, D., Ardito, B., Barcella, V., Capone, L., Nicolao, P., Lugaresi, A., Rini, A., Bianchi, M., Plasmati, I., Cocco, E., Docimo, R., De Luca, G., Mondino, F., Di Sapio, A., Clerici, R., Mascoli, N., Ferro, M. T., Chisari, C. G., Maimone, D., Strumia, S., Pugliatti, M., Cargnelutti, D., Caniatti, L. M., Avolio, C., Crociani, P., Amato, M. P., Massacesi, L., Malagu, S., Ribizzi, G., Inglese, M., Venturi, S., Gazzola, P., Pizio, N. R., Brichetto, G., Plewnia, K., Bellantonio, P., Balgera, R., De Robertis, F., Fermi, S., Fausto, F., Mazzoni, M., Meucci, G., Cartechini, E., Cavaletti, G., Buccafusca, M., Bramanti, P., Romeo, M., Rovaris, M., Ronzoni, M., Confalonieri, P., Chiveri, L., Bertora, P., Tonietti, S., De Riz, M., Protti, A., Sola, P., Maremmani, C., Lus, G., Gallo, A., Maniscalco, G. T., Morra, V. B., Cacchio, G., Iodice, R., Ragno, M., Sinisi, L., Cantello, R., Piras, M. L., Salemi, G., Cottone, S., Grimaldi, L. M. E., Corea, F., Santangelo, G., Immovili, P., Gallo, P., D'Andrea, F., Frittelli, C., Pasquali, L., Falcini, M., Granella, F., Pesci, I., Ancona, A. L., Bergamaschi, R., Di Napoli, M., Romano, S., Pozzilli, C., Mirabella, Massimiliano, Conte, A., Galgani, S., Peresson, M., Grasso, M. G., Ferraro, E., Capone, F., Marfia, G. A., de Pascalis, D., Piantadosi, C., Valeriani, M., Busillo, V., Barone, P., De Stefano, N., Ulivelli, M., Santuccio, G., Parodi, S., Bucello, S., Traccis, S., Zarbo, R., Tassinari, T., Bandini, F., Cavalla, P., Clerico, M., De Rosa, G., Bertolotto, A., Imperiale, D., Sarchielli, P., Celani, M. G., Vianello, M., Marini, B., Fortunato, M., Zaffaroni, M., Nasuelli, D., Banfi, P., Brioschi, A. M., Solaro, C., Quatrale, R., Rossi, P., Gajofatto, A., Battaglia, M. A., Capobianco, M., Patti, F., Comi, G., Giordano, A., Mirabella M. (ORCID:0000-0002-7783-114X), Lepore, V., Bosetti, C., Santucci, C., Iaffaldano, P., Trojano, M., Mosconi, P., Totaro, R., Coniglio, M. G., Bossio, R. B., Valentino, P., Gatto, M., Paolicelli, D., Ardito, B., Barcella, V., Capone, L., Nicolao, P., Lugaresi, A., Rini, A., Bianchi, M., Plasmati, I., Cocco, E., Docimo, R., De Luca, G., Mondino, F., Di Sapio, A., Clerici, R., Mascoli, N., Ferro, M. T., Chisari, C. G., Maimone, D., Strumia, S., Pugliatti, M., Cargnelutti, D., Caniatti, L. M., Avolio, C., Crociani, P., Amato, M. P., Massacesi, L., Malagu, S., Ribizzi, G., Inglese, M., Venturi, S., Gazzola, P., Pizio, N. R., Brichetto, G., Plewnia, K., Bellantonio, P., Balgera, R., De Robertis, F., Fermi, S., Fausto, F., Mazzoni, M., Meucci, G., Cartechini, E., Cavaletti, G., Buccafusca, M., Bramanti, P., Romeo, M., Rovaris, M., Ronzoni, M., Confalonieri, P., Chiveri, L., Bertora, P., Tonietti, S., De Riz, M., Protti, A., Sola, P., Maremmani, C., Lus, G., Gallo, A., Maniscalco, G. T., Morra, V. B., Cacchio, G., Iodice, R., Ragno, M., Sinisi, L., Cantello, R., Piras, M. L., Salemi, G., Cottone, S., Grimaldi, L. M. E., Corea, F., Santangelo, G., Immovili, P., Gallo, P., D'Andrea, F., Frittelli, C., Pasquali, L., Falcini, M., Granella, F., Pesci, I., Ancona, A. L., Bergamaschi, R., Di Napoli, M., Romano, S., Pozzilli, C., Mirabella, Massimiliano, Conte, A., Galgani, S., Peresson, M., Grasso, M. G., Ferraro, E., Capone, F., Marfia, G. A., de Pascalis, D., Piantadosi, C., Valeriani, M., Busillo, V., Barone, P., De Stefano, N., Ulivelli, M., Santuccio, G., Parodi, S., Bucello, S., Traccis, S., Zarbo, R., Tassinari, T., Bandini, F., Cavalla, P., Clerico, M., De Rosa, G., Bertolotto, A., Imperiale, D., Sarchielli, P., Celani, M. G., Vianello, M., Marini, B., Fortunato, M., Zaffaroni, M., Nasuelli, D., Banfi, P., Brioschi, A. M., Solaro, C., Quatrale, R., Rossi, P., Gajofatto, A., Battaglia, M. A., Capobianco, M., Patti, F., Comi, G., Giordano, A., and Mirabella M. (ORCID:0000-0002-7783-114X)
Abstract: Background and purpose: In relapsing-remitting multiple sclerosis patients (RRMS) disability progressively accumulates over time. To compare the cumulative probability of 6-month confirmed disability-worsening events using a fixed baseline or a roving Expanded Disability Status Scale (EDSS) reference, in a real-world setting. Methods: A cohort of 7964 RRMS patients followed for 2 or more years, with EDSS scores recorded every 6 months, was selected from the Italian Multiple Sclerosis Register. The overall probability of confirmed disability-worsening events and of confirmed disability-worsening events unrelated to relapse was evaluated using as reference a fixed baseline EDSS score or a roving EDSS score in which the increase had to be separated from the last EDSS assessment by at least 6 or 12 months. Results: Using a fixed baseline EDSS reference, the cumulative probability of 6-year overall confirmed disability-worsening events was 33.2%, and that of events unrelated to relapse was 10.9% (33% of overall confirmed disability-worsening events). Using a roving EDSS, the proportions were respectively 35.2% and 21.3% (61% of overall confirmed disability-worsening events). Conclusions: In a real-world setting, roving EDSS reference scores appear to be more sensitive for detecting confirmed disability-worsening events unrelated to relapse in RRMS patients.
Published: 2020

11. Effectiveness of Natalizumab on Multiple Sclerosis patients: the Italian registry experience

Author: Chisari, C., Comi, G., Zaffaroni, M., Morra, V. Brescia, Trojano, M., Iaffaldano, P., Cocco, E., Centonze, D., Uccelli, A., Pozzilli, C., Salemi, G., Luca, G., Cottone, S., Millefiorini, E., Salvetti, M., Aguglia, U., Costantino, G., Florio, C., Galgani, S., Pesci, I., Amato, M. P., Rovaris, M., Gazzola, P., Lus, G., Maimone, D., Grimaldi, L. M., Bergamaschi, R., Granella, F., Bertolotto, A., Totaro, R., Vianello, M., Bellantonio, P., Cavalla, P., Di Battista, G., Spitaleri, D., Tedeschi, G., Valzania, F., Scarpini, E., Gatto, M., Valentino, P., Renato Mantegazza, Rezzonico, M., Passarella, B., Avolio, C., Logullo, F. O., Cavalletti, G., Corea, F., Clerico, M., Lugaresi, A., and Patti, F.
Published: 2019

12. Environmental Factors and Their Regulation of Immunity in Multiple Sclerosis

Author: Trojano, M. and Avolio, C.
Subjects: Multiple sclerosis, Environment–immune interplay, Epigenetic mechanisms, Microbiota, Virus infection, Smoking, Environmental factors, Sunlight exposure, Vitamin D, Article
Abstract: In multiple sclerosis (MS), environmental factors and genetic traits cooperate in the induction of the chronic activation of immune cells to produce the brain pathology. Epidemiology has focused on different environmental risk factors but certainly virus infection, smoking, vitamin D levels, and sunlight exposure are the most relevant. What is certainly less clear is the way in which these external factors are able to induce and sustain the internal pathology process of the disease. Epigenetics has been recently focused on trying to shed light on this aspect. As a matter of fact epigenetic changes are highly sensitive to environmental factors that therefore may influence the susceptibility to the disease by acting through epigenetic modifications. In this chapter we discuss the most relevant environmental factors and how they may affect the immune response in MS. Finally, we discuss the possible role of the microbiota in inducing autoimmunity in MS.
Published: 2016

13. No evidence of disease activity (NEDA-3) and disability improvement after alemtuzumab treatment for multiple sclerosis: a 36-month real-world study

Author: Prosperini, L., Annovazzi, P., Boffa, L., Buscarinu, M. C., Gallo, A., Matta, M., Moiola, L., Musu, L., Perini, P., Avolio, C., Barcella, V., Bianco, Assunta, Farina, D., Ferraro, E., Pontecorvo, S., Granella, F., Grimaldi, L. M. E., Laroni, A., Lus, G., Patti, F., Pucci, E., Pasca, M., Sarchielli, P., Ghezzi, A., Zaffaroni, M., Baroncini, D., Buttari, F., Centonze, D., Fornasiero, A., Salvetti, M., Docimo, R., Signoriello, E., Tedeschi, G., Bertolotto, A., Capobianco, M., Comi, G., Cocco, E., Gallo, P., Puthenparampil, M., Grasso, R., Di Francescantonio, V., Rottoli, M. R., Mirabella, Massimiliano, Lugaresi, A., De Luca, G., Di Ioia, M., Di Tommaso, V., Mancinelli, L., Di Battista, G., Francia, A., Ruggieri, S., Pozzilli, C., Curti, E., Tsantes, E., Palmeri, B., Lapicci, C., Mancardi, G. L., Uccelli, A., Chisari, C., D'Amico, E., Cartechini, E., Repice, A. M., Magnani, E., Massaccesi, L., Calabresi, Paolo, Di Filippo, Mario, Di Gregorio, M., Bianco A., Mirabella M. (ORCID:0000-0002-7783-114X), Calabresi P. (ORCID:0000-0003-0326-5509), Di Filippo M., Prosperini, L., Annovazzi, P., Boffa, L., Buscarinu, M. C., Gallo, A., Matta, M., Moiola, L., Musu, L., Perini, P., Avolio, C., Barcella, V., Bianco, Assunta, Farina, D., Ferraro, E., Pontecorvo, S., Granella, F., Grimaldi, L. M. E., Laroni, A., Lus, G., Patti, F., Pucci, E., Pasca, M., Sarchielli, P., Ghezzi, A., Zaffaroni, M., Baroncini, D., Buttari, F., Centonze, D., Fornasiero, A., Salvetti, M., Docimo, R., Signoriello, E., Tedeschi, G., Bertolotto, A., Capobianco, M., Comi, G., Cocco, E., Gallo, P., Puthenparampil, M., Grasso, R., Di Francescantonio, V., Rottoli, M. R., Mirabella, Massimiliano, Lugaresi, A., De Luca, G., Di Ioia, M., Di Tommaso, V., Mancinelli, L., Di Battista, G., Francia, A., Ruggieri, S., Pozzilli, C., Curti, E., Tsantes, E., Palmeri, B., Lapicci, C., Mancardi, G. L., Uccelli, A., Chisari, C., D'Amico, E., Cartechini, E., Repice, A. M., Magnani, E., Massaccesi, L., Calabresi, Paolo, Di Filippo, Mario, Di Gregorio, M., Bianco A., Mirabella M. (ORCID:0000-0002-7783-114X), Calabresi P. (ORCID:0000-0003-0326-5509), and Di Filippo M.
Abstract: In this retrospective, multicenter, real-world study we collected clinical and magnetic resonance imaging (MRI) data of all patients (n = 40) with relapsing-remitting multiple sclerosis (RRMS) treated with alemtuzumab according to a “free-of-charge” protocol available before the drug marketing approval in Italy. Almost all (39/40) started alemtuzumab after discontinuing multiple disease-modifying treatments (DMTs) because of either lack of response or safety concerns. We considered the proportion of alemtuzumab-treated patients who had no evidence of disease activity (NEDA-3) and disability improvement over a 36-month follow-up period. NEDA-3 was defined as absence of relapses, disability worsening, and MRI activity. Disability improvement was defined as a sustained reduction of ≥ 1-point in Expanded Disability Status Scale (EDSS) score. At follow-up, 18 (45%) patients achieved NEDA-3, 30 (75%) were relapse-free, 33 (82.5%) were EDSS worsening-free, and 25 (62.5%) were MRI activity-free. Eleven (27.5%) patients had a sustained disability improvement. We found no predictor for the NEDA-3 status, while the interaction of higher EDSS score by higher number of pre-alemtuzumab relapses was associated with a greater chance of disability improvement (odds ratio 1.10, p = 0.049). Our study provides real-world evidence that alemtuzumab can promote clinical and MRI disease remission, as well as disability improvement, in a significant proportion of patients with RRMS despite prior multiple DMT failures. The drug safety profile was consistent with data available from clinical trials.
Published: 2018

14. Defining the electroclinical phenotype and outcome of PCDH19-related epilepsy: A multicenter study

Author: Trivisano, M., Pietrafusa, N., Terracciano, A., Marini, C., Mei, D., Darra, F., Accorsi, P., Battaglia, Domenica Immacolata, Caffi, L., Canevini, M. P., Cappelletti, S., Cesaroni, E., de Palma, L., Costa, Paolo, Cusmai, R., Giordano, Liliana, Ferrari, A., Freri, E., Fusco, L., Granata, T., Martino, T., Mastrangelo, Marica, Bova, S. M., Parmeggiani, L., Ragona, F., Sicca, F., Striano, P., Specchio, L. M., Tondo, I., Zambrelli, E., Zamponi, N., Zanus, C., Boniver, C., Vecchi, M., Avolio, C., Dalla Bernardina, B., Bertini, Enrico Silvio, Guerrini, R., Vigevano, F., Specchio, N., Battaglia D. (ORCID:0000-0003-0491-4021), Costa P., Giordano L., Mastrangelo M., Bertini E., Trivisano, M., Pietrafusa, N., Terracciano, A., Marini, C., Mei, D., Darra, F., Accorsi, P., Battaglia, Domenica Immacolata, Caffi, L., Canevini, M. P., Cappelletti, S., Cesaroni, E., de Palma, L., Costa, Paolo, Cusmai, R., Giordano, Liliana, Ferrari, A., Freri, E., Fusco, L., Granata, T., Martino, T., Mastrangelo, Marica, Bova, S. M., Parmeggiani, L., Ragona, F., Sicca, F., Striano, P., Specchio, L. M., Tondo, I., Zambrelli, E., Zamponi, N., Zanus, C., Boniver, C., Vecchi, M., Avolio, C., Dalla Bernardina, B., Bertini, Enrico Silvio, Guerrini, R., Vigevano, F., Specchio, N., Battaglia D. (ORCID:0000-0003-0491-4021), Costa P., Giordano L., Mastrangelo M., and Bertini E.
Abstract: Objective: PCDH19-related epilepsy is an epileptic syndrome with infantile onset, characterized by clustered and fever-induced seizures, often associated with intellectual disability (ID) and autistic features. The aim of this study was to analyze a large cohort of patients with PCDH19-related epilepsy and better define the epileptic phenotype, genotype-phenotype correlations, and related outcome-predicting factors. Methods: We retrospectively collected genetic, clinical, and electroencephalogram (EEG) data of 61 patients with PCDH19-related epilepsy followed at 15 epilepsy centers. All consecutively performed EEGs were analyzed, totaling 551. We considered as outcome measures the development of ID, autistic spectrum disorder (ASD), and seizure persistence. The analyzed variables were the following: gender, age at onset, age at study, genetic variant, fever sensitivity, seizure type, cluster occurrence, status epilepticus, EEG abnormalities, and cognitive and behavioral disorders. Receiver operating characteristic curve analysis was performed to evaluate the age at which seizures might decrease in frequency. Results: At last follow-up (median = 12 years, range = 1.9-42.1 years), 48 patients (78.7%) had annual seizures/clusters, 13 patients (21.3%) had monthly to weekly seizures, and 12 patients (19.7%) were seizure-free for ≥2 years. Receiver operating characteristic analysis showed a significant decrease of seizure frequency after the age of 10.5 years (sensitivity = 81.0%, specificity = 70.0%). Thirty-six patients (59.0%) had ID and behavioral disturbances. ASD was present in 31 patients. An earlier age at epilepsy onset emerged as the only predictive factor for ID (P = 0.047) and ASD (P = 0.014). Conversely, age at onset was not a predictive factor for seizure outcome (P = 0.124). Significance: We found that earlier age at epilepsy onset is related to a significant risk for ID and ASD. Furthermore, long-term follow-up showed that after the age of 10 years, seizur
Published: 2018

15. Safety of the first dose of fingolimod for multiple sclerosis: results of an open-label clinical trial

Author: Laroni A., Brogi D., Morra V. B., Guidi L., Pozzilli C., Comi G., Lugaresi A., Turrini R., Raimondi D., Uccelli A., Mancardi G. L., Amato M. P., Appendino L., Ardito B., Avolio C., Bandini F., Batocchi A. P., Bellantonio P., Benedetti M. D., Bergamaschi R., Bortolon F., Bosco A., Buccafusca M., Cargnelutti D., Cavalla P., Cavallo R., Centonze D., Coniglio M. G., Costantino G., Cottone S., Danni M. C., De Robertis F., Deotto L., Dotta M., Di Battista G., Filippi M. M., Florio C., Francia A., Galgani S., Gallo P., Ghezzi A., Giometto B., Giuliani G., Grimaldi L. M. E., Guidotti M., Iudice A., Lenzi G. L., Lorusso L., Lus G., Maimone D., Malentacchi G. M., Mantegazza R. E., Massacesi L., Melato M., Millefiorini E., Montanari E., Patti F., Perrone P. S. M., Protti A., Provera P., Quattrone A., Rasi F., Rosati G., Rovaris M., Sacca F., Salemi G., Sarchielli P., Scarpini E. A., Schoenhuber R., Serrati C., Sinisi L., Sola P., Spitaleri D. L. A., Tedeschi G., Tezzon F., Tinebra Asti M. C., Tola M. R., Totaro R., Trojano M., Ulivelli M., Vecchio M. M., Zimatore G. B., Alice Laroni, Davide Brogi, Vincenzo Brescia Morra, Leonello Guidi, Carlo Pozzilli, Giancarlo Comi, Alessandra Lugaresi, Renato Turrini, Debora Raimondi, Antonio Uccelli, Giovanni Mancardi, EAP Investigators, Laroni, A, Brogi, D, BRESCIA MORRA, Vincenzo, Guidi, L, Pozzilli, C, Comi, G, Lugaresi, A, Turrini, R, Raimondi, D, Uccelli, A, Macardi, G., Laroni A, Brogi D, Morra VB, Guidi L, Pozzilli C, Comi G, Lugaresi A, Turrini R, Raimondi D, Uccelli A, Mancardi GL, Amato MP, Appendino L, Ardito B, Avolio C, Bandini F, Batocchi AP, Bellantonio P, Benedetti MD, Bergamaschi R, Bortolon F, Bosco A, Buccafusca M, Cargnelutti D, Cavalla P, Cavallo R, Centonze D, Coniglio MG, Costantino G, Cottone S, Danni MC, De Robertis F, Deotto L, Dotta M, Di Battista G, Filippi MM, Florio C, Francia A, Galgani S, Gallo P, Ghezzi A, Giometto B, Giuliani G Grimaldi LME, Guidotti M, Iudice A, Lenzi GL, Lorusso L, Lus G, Maimone D, Malentacchi GM, Mantegazza RE, Massacesi L, Melato M, Millefiorini E, Montanari E, Patti F, Perrone PSM, Protti A, Provera P, Quattrone A, Rasi F, Rosati G, Rovaris M, Saccà F, Salemi G, Sarchielli P, Scarpini EA, Schoenhuber R, Serrati C, Sinisi L, Sola P, Spitaleri DLA, Tedeschi G, Tezzon F, Tinebra Asti MC, Tola MR, Totaro R, Trojano M, Ulivelli M, Vecchio MM, Zimatore GB, Laroni, A., Brogi, D., Morra, V. B., Guidi, L., Pozzilli, C., Comi, G., Lugaresi, A., Turrini, R., Raimondi, D., Uccelli, A., Mancardi, G. L., Amato, M. P., Appendino, L., Ardito, B., Avolio, C., Bandini, F., Batocchi, A. P., Bellantonio, P., Benedetti, M. D., Bergamaschi, R., Bortolon, F., Bosco, A., Buccafusca, M., Cargnelutti, D., Cavalla, P., Cavallo, R., Centonze, D., Coniglio, M. G., Costantino, G., Cottone, S., Danni, M. C., De Robertis, F., Deotto, L., Dotta, M., Di Battista, G., Filippi, M. M., Florio, C., Francia, A., Galgani, S., Gallo, P., Ghezzi, A., Giometto, B., Giuliani, G., Grimaldi, L. M. E., Guidotti, M., Iudice, A., Lenzi, G. L., Lorusso, L., Lus, G., Maimone, D., Malentacchi, G. M., Mantegazza, R. E., Massacesi, L., Melato, M., Millefiorini, E., Montanari, E., Patti, F., Perrone, P. S. M., Protti, A., Provera, P., Quattrone, A., Rasi, F., Rosati, G., Rovaris, M., Sacca, F., Salemi, G., Sarchielli, P., Scarpini, E. A., Schoenhuber, R., Serrati, C., Sinisi, L., Sola, P., Spitaleri, D. L. A., Tedeschi, G., Tezzon, F., Tinebra Asti, M. C., Tola, M. R., Totaro, R., Trojano, M., Ulivelli, M., Vecchio, M. M., Zimatore, G. B., Mancardi, Gl, Brescia Morra, V, on behalf of the EAP, Investigator, and Giometto, B
Subjects: Oncology, Male, Neurology, fingolimod, multiple sclerosis, treatment, first dose, safety, administration /&/ dosage/adverse effects/analogs /&/ derivatives/therapeutic use, Immunosuppressive Agent, Sphingosine, Multiple Sclerosi, Atrioventricular Block, administration /&/ dosage/adverse effects/therapeutic use, General Medicine, Middle Aged, Tolerability, Propylene Glycol, Fingolimod, drug therapy, Anesthesia, Cohort, Adolescent, Adult, Atrioventricular Block, chemically induced/epidemiology, Drug Therapy, Combination, Female, Humans, Immunosuppressive Agents, administration /&/ dosage/adverse effects/therapeutic use, Male, Middle Aged, Multiple Sclerosis, drug therapy, Propylene Glycols, administration /&/ dosage/adverse effects/therapeutic use, Sphingosine, administration /&/ dosage/adverse effects/analogs /&/ derivatives/therapeutic use, Young Adult, Combination, Drug Therapy, Combination, Settore MED/26 - Neurologia, Female, Atrioventricular block, Bradycardia, Multiple sclerosis, Safety, Adolescent, Adult, Fingolimod Hydrochloride, Humans, Immunosuppressive Agents, Multiple Sclerosis, Propylene Glycols, Young Adult, Neurology (clinical), Atrioventricular block, Bradicardia, Multiple sclerosis, Fingolimod, Safety Tolerability, Research Article, Human, medicine.drug, medicine.medical_specialty, Clinical Neurology, Internal medicine, medicine, Neurochemistry, business.industry, medicine.disease, Clinical trial, Atrioventricular block, Bradycardia, Multiple sclerosis, Fingolimod, Safety, Tolerability, chemically induced/epidemiology, business
Abstract: BACKGROUND: In patients with relapsing-remitting MS (RRMS) fingolimod prevents disease relapses and delays disability progression. First dose administration of fingolimod is associated with a transient, dose-dependent decrease in heart rate (HR) in the 6 hours after drug intake.The aim of the study is to to assess safety and tolerability of the first dose of fingolimod in a cohort of Italian patients with RRMS without alternative therapeutic options. METHODS: Open-label, single arm, multicentre study. After the first dose of fingolimod, patients were observed for 6 hours and had their vital signs monitored hourly. Extended on-site monitoring was provided when required. RESULTS: Of the 906 patients enrolled in the study, most (95.2%) did not experience any adverse event (AE) following fingolimod administration. Cardiovascular AEs occurred in 18 patients and included bradycardia (1.3%), first-and second-degree atrioventricular block (0.1% and 0.2%), palpitations (0.1%), sinus arrhythmia (0.1%) and ventricular premature beats (0.1%). All events were self-limiting and did not require any intervention. Extended monitoring was required in 34 patients. CONCLUSIONS: These results, in a population who better resembled real-world clinical practice in terms of concomitant diseases and medications, are consistent with previous clinical trials and confirmed that the first dose administration of fingolimod is generally safe and well tolerated. TRIAL REGISTRATION: EudraCT 2011-000770-60.
Published: 2014

16. Prognostic Indicators in Pediatric Clinically Isolated Syndrome

Author: Iaffaldano, P, Simone, M, Lucisano, G, Ghezzi, A, Coniglio, G, Morra, VB, Salemi, G, Patti, F, Lugaresi, A, Izquierdo, G, Bergamaschi, R, Cabrera-Gomez, JA, Pozzilli, C, Millefiorini, E, Alroughani, R, Boz, C, Pucci, E, Zimatore, GB, Sola, P, Lus, G, Maimone, D, Avolio, C, Cocco, E, Sajedi, SA, Costantino, G, Duquette, P, Shaygannejad, V, Petersen, T, Fernandez Bolanos, R, Paolicelli, D, Tortorella, C, Spelman, T, Margari, L, Amato, MP, Comi, G, Butzkueven, H, Trojano, M, Iaffaldano, P, Simone, M, Lucisano, G, Ghezzi, A, Coniglio, G, Morra, VB, Salemi, G, Patti, F, Lugaresi, A, Izquierdo, G, Bergamaschi, R, Cabrera-Gomez, JA, Pozzilli, C, Millefiorini, E, Alroughani, R, Boz, C, Pucci, E, Zimatore, GB, Sola, P, Lus, G, Maimone, D, Avolio, C, Cocco, E, Sajedi, SA, Costantino, G, Duquette, P, Shaygannejad, V, Petersen, T, Fernandez Bolanos, R, Paolicelli, D, Tortorella, C, Spelman, T, Margari, L, Amato, MP, Comi, G, Butzkueven, H, and Trojano, M
Abstract: OBJECTIVE: To assess prognostic factors for a second clinical attack and a first disability-worsening event in pediatric clinically isolated syndrome (pCIS) suggestive of multiple sclerosis (MS) patients. METHODS: A cohort of 770 pCIS patients was followed up for at least 10 years. Cox proportional hazard models and Recursive Partitioning and Amalgamation (RECPAM) tree-regression were used to analyze data. RESULTS: In pCIS, female sex and a multifocal onset were risk factors for a second clinical attack (hazard ratio [HR], 95% confidence interval [CI] = 1.28, 1.06-1.55; 1.42, 1.10-1.84, respectively), whereas disease-modifying drug (DMD) exposure reduced this risk (HR, 95% CI = 0.75, 0.60-0.95). After pediatric onset MS (POMS) diagnosis, age at onset younger than 15 years and DMD exposure decreased the risk of a first Expanded Disability Status Scale (EDSS)-worsening event (HR, 95% CI = 0.59, 0.42-0.83; 0.75, 0.71-0.80, respectively), whereas the occurrence of relapse increased this risk (HR, 95% CI = 5.08, 3.46-7.46). An exploratory RECPAM analysis highlighted a significantly higher incidence of a first EDSS-worsening event in patients with multifocal or isolated spinal cord or optic neuritis involvement at onset in comparison to those with an isolated supratentorial or brainstem syndrome. A Cox regression model including RECPAM classes confirmed DMD exposure as the most protective factor against EDSS-worsening events and relapses as the most important risk factor for attaining EDSS worsening. INTERPRETATION: This work represents a step forward in identifying predictors of unfavorable course in pCIS and POMS and supports a protective effect of early DMD treatment in preventing MS development and disability accumulation in this population. Ann Neurol 2017;81:729-739.
Published: 2017

17. Predictors of definite Multiple Sclerosis in patients with pediatric onset first demyelinating clinical attack

Author: SALEMI, Giuseppe, Iaffaldano P, Lucisano G, Ghezzi A, Comi V, Brescia Morra V, Patti F, Lugaresi A, Pozzilli C, Amato M, Millefiorini E, Lus G, Zimatore G, Maimone D, Coniglio G, Bergamaschi R, Marrosu M, Tedeschi G, Ardito D, Giuliani G, Avolio C, Montanari E, Simone M, Margari L, Lepore V, Trojano M., Salemi, G, and Iaffaldano P, Lucisano G, Ghezzi A, Comi V, Brescia Morra V, Patti F, Lugaresi A, Pozzilli C, Amato M, Millefiorini E, Lus G, Zimatore G, Maimone D, Coniglio G, Bergamaschi R, Marrosu M, Tedeschi G, Ardito D, Giuliani G, Avolio C, Montanari E, Simone M, Margari L, Lepore V, Trojano M
Subjects: Multiple Sclerosis, pediatric onset, Settore MED/26 - Neurologia
Published: 2014

18. Post-marketing of disease modifying drugs in multiple sclerosis: an exploratory analysis of gender effect in interferon beta treatment

Author: Trojano, M, Pellegrini, F, Paolicelli, D, Fuiani, A, Zimatore, Gb, Tortorella, C, Simone, Il, Patti, F, Ghezzi, A, Portaccio, E, Rossi, P, Pozzilli, C, Salemi, G, Lugaresi, A, Bergamaschi, R, Millefiorini, E, Clerico, Marinella, Lus, G, Vianello, M, Avolio, C, Cavalla, P, Iaffaldano, P, Direnzo, V, D'Onghia, M, Lepore, V, Livrea, P, Comi, G, Amato, Mp, Italian Multiple Sclerosis Database Network Group, Trojano, M., Pellegrini, F., Paolicelli, D., Fuiani, A., Zimatore, G., Tortorella, C., Simone, I., Patti, F., Ghezzi, A., Portaccio, E., Rossi, P., Pozzilli, C., Salemi, G., Lugaresi, A., Bergamaschi, R., Millefiorini, E., Clerico, M., Lus, Giacomo, Vianello, M., Avolio, C., Cavalla, P., Iaffaldano, P., Direnzo, V., D'Onghia, M., Lepore, V., Livrea, P., Comi, G., Amato, M., ITALIAN MULTIPLE SCLEROSIS DATABASE NETWORK, . ., Trojano M, Pellegrini F, Paolicelli D, Fuiani A, Zimatore GB, Tortorella C, Simone IL, Patti F, Ghezzi A, Portaccio E, Rossi P, Pozzilli C, Salemi G, Lugaresi A, Bergamaschi R, Millefiorini E, Clerico M, Lus G, Vianello M, Avolio C, Cavalla P, Iaffaldano P, Direnzo V, D'Onghia M, Lepore V, Livrea P, Comi G, Amato MP, M Trojano, F Pellegrini, D Paolicelli, A Fuiani, GB Zimatore, C Tortorella C, IL Simone, F Patti, A Ghezzi, E Portaccio, P Rossi, C Pozzilli, G Salemi, A Lugaresi, and on behalf of Italian Multiple Sclerosis Database Network (MSDN) group
Subjects: Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Propensity score, Disease, gender, interferon beta, multiple sclerosis, observational study, propensity score, Lower risk, Severity of Illness Index, Multiple sclerosis, Interferon beta, Gender, Observational study, Propensity score, Cohort Studies, Disability Evaluation, Young Adult, Sex Factors, gender, multiple sclerosis, treatment, interferon, Double-Blind Method, Internal medicine, Observational study, medicine, Confidence Intervals, Odds Ratio, Product Surveillance, Postmarketing, Humans, Immunologic Factors, Multiple sclerosi, Proportional Hazards Models, Expanded Disability Status Scale, Proportional hazards model, business.industry, Multiple sclerosis, Drug Administration Routes, Interferon-beta, medicine.disease, Interferon beta, Surgery, Neurology, Italy, Cohort, Propensity score matching, Regression Analysis, Settore MED/26 - Neurologia, Female, Neurology (clinical), business
Abstract: Background: There are a few and conflicting results from randomised controlled trials (RCTs) pertaining to the influence of gender in response to currently used disease modifying drugs in Multiple Sclerosis (MS). Observational studies may be especially valuable for answering effectiveness questions in subgroups not studied in RCTs. Objective: To conduct a post-marketing analysis aimed to evaluate the gender effect on Interferon beta (IFN beta) treatment response in a cohort of relapsing (RR) MS patients. Methods: A cohort of 2570 IFN beta-treated RRMS was prospectively followed for Lip to 7 years in 15 Italian MS Centers. Cox proportional hazards regression models were used to assess gender differences for risk of reaching 1st relapse and risk of progression by I point on Expanded Disability Status Scale (EDSS) score. Gender effects were also explored by a propensity score (PS) matching algorithm, and a tree-growing technique. Results: The multivariate Cox Regression analyses showed that male patients had a significant (p = 0.0097) lower risk for 1st relapse and a trend (p = 0.0897) for a higher risk to reach I point EDSS progression than females. The PS matched multivariate Cox Regression confirmed these results. The RECPAM analysis showed that male sex conferred a significant reduction in the risk for 1st relapse (HR = 0.86; 95% Cl = 0.76-0.98; p = 0.0226) in the subgroup with a low pre-treatment number of bouts, and a significant increase in the risk for I point EDSS progression (HR = 1.33; 95% Cl: 1.00-1.76; p
Published: 2009

19. Real-life impact of early interferon beta therapy in relapsing multiple sclerosis

Author: Trojano, M., Pellegrini, F., Paolicelli, D., Fuiani, A., Zimatore, G., Tortorella, C., Simone, I., Patti, F., Ghezzi, A., Zipoli, V., Rossi, P., Pozzilli, C., Salemi, G., Lugaresi, A., Bergamaschi, R., Millefiorini, E., Clerico, M., Lus, G., Vianello, M., Avolio, C., Cavalla, P., Lepore, V., Livrea, P., Comi, G., Amato, M., Di Monte, E., Iaffaldano, P., Direnzo, V., D'Onghia, M., Lo Fermo, S., Messina, S., D'Amico, E., Rizzo, A., Zaffaroni, M., Portaccio, E., Martinelli, V., Prosperini, L., Onesti, E., Aridon, P., D'Amelio, M., Ragonese, P., De Luca, G., Farina, D., Di Tommaso, V., Tavazzi, E., Bargiggia, V., Crivelli, P., Cortese, A., Di Rezze, S., Durastanti, V., Alfieri, G., Rosellini, I., Modesto, M., Notariello, M., Tortorella, P., Trojano M, Pellegrini F, Paolicelli D, Fuiani A, Zimatore GB, Tortorella C, Simone IL, Patti F, Ghezzi A, Zipoli V, Rossi P, Pozzilli C, Salemi G, Lugaresi A, Bergamaschi R, Millefiorini E, Clerico M, Lus G, Vianello M, Avolio C, Cavalla P, Lepore V, Livrea P, Comi G, Amato MP, Di Monte E, Iaffaldano P, Direnzo V, D'Onghia M, Lo Fermo S, Messina S, D'Amico E, Rizzo A, Zaffaroni M, Portaccio E, Martinelli V, Prosperini L, Onesti E, Aridon P, D'Amelio M, Ragonese P, De Luca G, Farina D, Di Tommaso V, Tavazzi E, Bargiggia V, Crivelli P, Cortese A, Di Rezze S, Durastanti V, Alfieri G, Rosellini I, Modesto M, Notariello M, Tortorella P, Trojano, M, Pellegrini, F, Paolicelli, D, Fuiani, A, Zimatore, Gb, Tortorella, C, Simone, Il, Patti, F, Ghezzi, A, Zipoli, V, Rossi, P, Pozzilli, C, Salemi, G, Lugaresi, Alessandra, Bergamaschi, R, Millefiorini, E, Clerico, M, Lus, G, Vianello, M, Avolio, C, Cavalla, P, Lepore, V, Livrea, P, Comi, G, and Amato, Mp
Subjects: Adult, Male, Time Factors, Multiple Sclerosis, Interferon beta, Interferon-beta, Cohort Studies, Young Adult, Multiple Sclerosis, Relapsing-Remitting, Treatment Outcome, observational study, multiple sclerosis, interferon, treatment, early, Sickness Impact Profile, Multiple Sclerosi, Quality of Life, Humans, Female, Settore MED/26 - Neurologia, Prospective Studies, Follow-Up Studies
Abstract: OBJECTIVE: Recent findings support greater efficacy of early vs. delayed interferon beta (IFNbeta) treatment in patients with a first clinical event suggestive of multiple sclerosis (MS). We aimed to evaluate the effectiveness of early IFNbeta treatment in definite relapsing-remitting MS (RRMS) and to assess the optimal time to initiate IFNbeta treatment with regard to the greatest benefits on disability progression. METHODS: A cohort of 2,570 IFNbeta-treated RRMS patients was prospectively followed for up to 7 years in 15 Italian MS Centers. A Cox proportional hazards regression model adjusted for propensity score (PS) quintiles was used to assess differences between groups of patients with early vs. delayed IFNbeta treatment on risk of reaching a 1-point progression in the Expanded Disability Status Scale (EDSS) score, and the EDSS 4.0 and 6.0 milestones. A set of PS-adjusted Cox hazards regression models were calculated according to different times of treatment initiation (within 1 year up to within 5 years from disease onset). A sensitivity analysis was performed to assess the robustness of findings. RESULTS: The lowest hazard ratios (HRs) for the three PS quintiles-adjusted models were obtained by a cutoff of treatment initiation within 1 year from disease onset. Early treatment significantly reduced the risk of reaching a 1-point progression in EDSS score (HR = 0.63; 95% CI = 0.48-0.85; p < 0.002), and the EDSS 4.0 milestone (HR = 0.56; 95% CI = 0.36-0.90; p = 0.015). Sensitivity analysis showed the bound of significance for unmeasured confounders. INTERPRETATION: Greater benefits on disability progression may be obtained by an early IFNbeta treatment in RRMS.
Published: 2009

20. post marketing of disease modifying drugs in multiple sclerosis: an exploratory analysis of gender effect in intereron beta treatment

Author: TROJANO M, PELLEGRINI F, PAOLICELLI D, FUIANI A, ZIMATORE GB, TORTORELLA C, SIMONE IL, PATTI F, GHEZZI A, PORTACCIO E, ROSSI P, POZZILLI C, SALEMI G, LUGARESI A, BERGAMASCHI R, MILLEFIORINI E, CLERICO M, LUS G, VIANELLO M, AVOLIO C, CAVALLA P, IAFFALDANO P, DIRENZO V, D'ONGHIA M, LEPORE V, LIVREA P, AMATO MP, ITALIAN MULTIPLE SCLEROSIS DATABASE NETWORK GROUP, COMI , GIANCARLO, Trojano, M, Pellegrini, F, Paolicelli, D, Fuiani, A, Zimatore, Gb, Tortorella, C, Simone, Il, Patti, F, Ghezzi, A, Portaccio, E, Rossi, P, Pozzilli, C, Salemi, G, Lugaresi, A, Bergamaschi, R, Millefiorini, E, Clerico, M, Lus, G, Vianello, M, Avolio, C, Cavalla, P, Iaffaldano, P, Direnzo, V, D'Onghia, M, Lepore, V, Livrea, P, Comi, Giancarlo, Amato, Mp, and ITALIAN MULTIPLE SCLEROSIS DATABASE NETWORK, Group
Published: 2009

21. rel-life impact of early interferon beta therapy in relapsing multiple sclerosis

Author: TROJANO M, PELLEGRINI F, PAOLICELLI D, FUIANI A, ZIMATORE GB, TORTORELLA C, SIMONE IL, PATTI F, GHEZZI A, ZIPOLI V, ROSSI P, POZZILLI C, SALEMI G, LUGARESI A, BERGAMASCHI R, MILLEFIORINI E, CLERICO M, LUS G, VIANELLO M, AVOLIO C, CAVALLA P, LEPORE V, LIVREA P, AMATO MP, ITALIAN MULTIPLE SCLEROISS DATABASE NETWORK MSDN GROUP, COMI , GIANCARLO, Trojano, M, Pellegrini, F, Paolicelli, D, Fuiani, A, Zimatore, Gb, Tortorella, C, Simone, Il, Patti, F, Ghezzi, A, Zipoli, V, Rossi, P, Pozzilli, C, Salemi, G, Lugaresi, A, Bergamaschi, R, Millefiorini, E, Clerico, M, Lus, G, Vianello, M, Avolio, C, Cavalla, P, Lepore, V, Livrea, P, Comi, Giancarlo, Amato, Mp, and ITALIAN MULTIPLE SCLEROISS DATABASE NETWORK MSDN, Group
Published: 2009

22. Serial immunoprecipitation assays for interferon (IFN) beta antibodies in multiple sclerosis patients

Author: Lampasona V, Rio J, Franciotta D, Furlan R, Avolio C, Fazio R, Lavolpe V, Vincent A, COMI , GIANCARLO, Trojano M, Montalban X, MARTINO , GIANVITO, Lampasona, V, Rio, J, Franciotta, D, Furlan, R, Avolio, C, Fazio, R, Lavolpe, V, Vincent, A, Comi, Giancarlo, Trojano, M, Montalban, X, and Martino, Gianvito
Published: 2003

23. Gender ratio of multiple sclerosis in Italy: geographical distribution and trend over 60 years

Author: Lucchese, G, D'Onghia, M, Patti, Francesco, Pozzilli, C, Amato, M, Lugaresi, A, Ghezzi, A, Millefiorini, E, Marrosu, M, Salemi, G, Comi, G, Lus, G, Bergamaschi, R, Montanari, E, Giuliani, G, Vianello, M, Cogniglio, G, Cavalla, P, Granella, F, Rottoli, M, Granieri, E, Tedeschi, G, Avolio, C, Ardito, B, Gallo, P, Zorzon, M, DI BATTISTA, G, Ferrò, M, Scarpini, E, Sola, P, Carrieri, P, Graziano, G, Lepore, V, and Trojano, M.
Published: 2010

24. Heterogeneous impact of an early IFN-Beta treatment on disability progression in relapsing MS subgroups with different baseline clinicale profiles

Author: Trojano, M, Amato, Mp, Avolio, C, Bergamaschi, R, Cavalla, P, Durelli, L, Fuiani, A, Ghezzi, A, Giuliani, G, Lugaresi, A, Lus, G, Millefiorini, E, Paolicelli, D, Patti, Francesco, Pellegrini, F, Pozzilli, C, Rossi, P, Salemi, G, Vianello, M, Livrea, P, and Comi, G.
Published: 2007

25. Disease-Modifying Treatments and Time to Loss of Ambulatory Function in Patients with Primary Progressive Multiple Sclerosis

Author: Emilio, Portaccio, Mattia, Fonderico, Pietro, Iaffaldano, Luisa, Pastò, Lorenzo, Razzolini, Angelo, Bellinvia, Giovanna, De Luca, Paolo, Ragonese, Francesco, Patti, Vincenzo, Brescia Morra, Eleonora, Cocco, Patrizia, Sola, Matilde, Inglese, Giacomo, Lus, Carlo, Pozzilli, Davide, Maimone, Alessandra, Lugaresi, Paola, Gazzola, Giancarlo, Comi, Ilaria, Pesci, Daniele, Spitaleri, Marta, Rezzonico, Marika, Vianello, Carlo, Avolio, Francesco O, Logullo, Franco, Granella, Marco, Salvetti, Mauro, Zaffaroni, Giuseppe, Lucisano, Massimo, Filippi, Maria, Trojano, Maria Pia, Amato, Alessandra, Protti, Portaccio, E, Fonderico, M, Iaffaldano, P, Pasto, L, Razzolini, L, Bellinvia, A, De Luca, G, Ragonese, P, Patti, F, Brescia Morra, V, Cocco, E, Sola, P, Inglese, M, Lus, G, Pozzilli, C, Maimone, D, Lugaresi, A, Gazzola, P, Comi, G, Pesci, I, Spitaleri, D, Rezzonico, M, Vianello, M, Avolio, C, Logullo, F, Granella, F, Salvetti, M, Zaffaroni, M, Lucisano, G, Filippi, M, Trojano, M, Amato, M, Cavaletti, G, Portaccio, Emilio, Fonderico, Mattia, Iaffaldano, Pietro, Pastò, Luisa, Razzolini, Lorenzo, Bellinvia, Angelo, De Luca, Giovanna, Ragonese, Paolo, Patti, Francesco, Brescia Morra, Vincenzo, Cocco, Eleonora, Sola, Patrizia, Inglese, Matilde, Lus, Giacomo, Pozzilli, Carlo, Maimone, Davide, Lugaresi, Alessandra, Gazzola, Paola, Comi, Giancarlo, Pesci, Ilaria, Spitaleri, Daniele, Rezzonico, Marta, Vianello, Marika, Avolio, Carlo, Logullo, Francesco O, Granella, Franco, Salvetti, Marco, Zaffaroni, Mauro, Lucisano, Giuseppe, Filippi, Massimo, Trojano, Maria, and Amato, Maria Pia
Subjects: Adult, Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Recurrence, Retrospective Studie, Multiple Sclerosi, Disease Progression, Humans, Female, Neurology (clinical), Multiple Sclerosis, Chronic Progressive, Retrospective Studies, Human
Abstract: Importance: Except for ocrelizumab, treatment options in primary progressive multiple sclerosis (PPMS) are lacking. Objective: To investigate the effectiveness of DMTs on the risk of becoming wheelchair dependent in a real-world population of patients with PPMS. Design, Setting, and Participants: This was a multicenter, observational, retrospective, comparative effectiveness research study. Data were extracted on November 28, 2018, from the Italian multiple sclerosis register and analyzed from June to December 2021. Mean study follow-up was 11 years. Included in the study cohort were patients with a diagnosis of PPMS and at least 3 years of Expanded Disability Status Scale (EDSS) evaluations and 3 years of follow-up. Main Outcomes and Measures: The risk of reaching an EDSS score of 7.0 was assessed through multivariable Cox regression models. Exposures: Patients who received DMT before the outcome were considered treated. DMT was assessed as a time-dependent variable and by class of DMT (moderately and highly effective). Results: From a total of 3298 patients with PPMS, 2633 were excluded because they did not meet the entry criteria for the phase 3, multicenter, randomized, parallel-group, double-blind, placebo-controlled study to evaluate the efficacy and safety of ocrelizumab in adults with PPMS (ORATORIO) trial. Among the remaining 665 patients (mean [SD] age, 43.0 [10.7] years; 366 female patients [55.0%]), 409 were further selected for propensity score matching (288 treated and 121 untreated patients). In the matched cohort, during the study follow-up, 37% of patients (152 of 409) reached an EDSS score of 7.0 after a mean (SD) follow-up of 10.6 (5.6) years. A higher EDSS score at baseline (adjusted hazard ratio [aHR], 1.32; 95% CI, 1.13-1.55; P
Published: 2022

26. Injectable Versus Oral First-Line Disease-Modifying Therapies: Results from the Italian MS Register

Author: Marco Onofrj, Giacomo Lus, Damiano Paolicelli, Matilde Inglese, Giorgia Teresa Maniscalco, Massimo Filippi, Emanuele D'Amico, M. Vianello, Simonetta Galgani, Vincenzo Brescia Morra, Francesco Patti, Antonio Gallo, Aurora Zanghì, Paolo Confalonieri, Giuseppe Salemi, Giovanna De Luca, Maria Trojano, Carlo Avolio, Maria Pia Amato, Eleonora Cocco, Marzia Romeo, D'Amico, E., Zanghi, A., Romeo, M., Cocco, E., Maniscalco, G. T., Brescia Morra, V., Paolicelli, D., De Luca, G., Galgani, S., Amato, M. P., Salemi, G., Inglese, M., Confalonieri, P. A., Lus, G., Avolio, C., Gallo, A., Vianello, M., Onofrj, M., Filippi, M., Trojano, M., Patti, F., D'Amico, Emanuele, Zanghì, Aurora, Romeo, Marzia, Cocco, Eleonora, Maniscalco, Giorgia Teresa, Brescia Morra, Vincenzo, Paolicelli, Damiano, De Luca, Giovanna, Galgani, Simonetta, Amato, Maria Pia, Salemi, Giuseppe, Inglese, Matilde, Confalonieri, Paolo Agostino, Lus, Giacomo, Avolio, Carlo, Gallo, Antonio, Vianello, Marika, Onofrj, Marco, Filippi, Massimo, Trojano, Maria, and Patti, Francesco
Subjects: Male, oral DMTs, oral DMT, Administration, Oral, Disease, Relapsing-Remitting, Cohort Studies, 0302 clinical medicine, Immunologic, injectable DMT, Pharmacology (medical), 030212 general & internal medicine, Registries, Subcutaneous, Middle Aged, Italy, EDSS score, injectable DMTs, Multiple sclerosis, real-world setting, Adjuvants, Immunologic, Adult, Female, Follow-Up Studies, Glatiramer Acetate, Humans, Immunologic Factors, Injections, Subcutaneous, Interferon-beta, Multiple Sclerosis, Relapsing-Remitting, Retrospective Studies, Administration, Cohort, Settore MED/26 - Neurologia, Original Article, Neurosurgery, Cohort study, Oral, medicine.medical_specialty, Lower risk, Injections, 03 medical and health sciences, Internal medicine, medicine, Multiple sclerosi, Adjuvants, Pharmacology, business.industry, medicine.disease, Discontinuation, Observational study, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: The current study aims to compare injectable and oral first-line disease-modifying therapies (DMTs) for time to first relapse, time to confirmed disability progression (CDP), and time to discontinuation using a cohort of relapsing remitting multiple sclerosis (RRMS) patients, with data extracted from the Italian MS Register. This multicenter, observational, retrospectively acquired, and propensity-adjusted cohort study utilized RRMS-naïve patients from the Italian MS Register who started either injectable or oral first-line DMTs between January 1, 2010, and December 31, 2017, to evaluate the impact on disability outcomes in patients. Enrolled patients were divided into two groups, namely the injectable group (IG) and the oral group (OG). Of a cohort of 11,416 patients, 4602 were enrolled (3919 in the IG and 683 in the OG). The IG had a higher rate of women (67.3% vs 63.4%, p p p p = 0.941), while a lower risk of DMT was found in the OG (HR = 0.72; CI 95% 0.58–0.88, p = 0.002) for the event time to discontinuation. Real-world data from the Italian MS Register suggests that first-line oral DMTs are associated with a lower risk of experiencing a new relapse and of therapy discontinuation compared to injectable DMTs.
Published: 2021

27. Exit Strategies in Natalizumab-Treated RRMS at High Risk of Progressive Multifocal Leukoencephalopathy: a Multicentre Comparison Study

Author: Gianmarco Abbadessa, Carlo Avolio, Patrizia Sola, Franco Granella, Graziella Callari, Stefania Barone, Elisabetta Signoriello, Simona Bonavita, Francesco Patti, Aurora Zanghì, Maria Buccafusca, Valeria Di Francescantonio, Antonio Gallo, Rocco Capuano, Diana Ferraro, Roberta Lanzillo, Paola Valentino, Matteo Lucchini, Erica Curti, Giuseppe Pontillo, Massimiliano Mirabella, Emanuele D'Amico, Maria Petracca, Giacomo Lus, Zanghì, Aurora, Gallo, Antonio, Avolio, Carlo, Capuano, Rocco, Lucchini, Matteo, Petracca, Maria, Bonavita, Simona, Lanzillo, Roberta, Ferraro, Diana, Curti, Erica, Buccafusca, Maria, Callari, Graziella, Barone, Stefania, Pontillo, Giuseppe, Abbadessa, Gianmarco, Di Francescantonio, Valeria, Signoriello, Elisabetta, Lus, Giacomo, Sola, Patrizia, Granella, Franco, Valentino, Paola, Mirabella, Massimiliano, Patti, Francesco, D'Amico, Emanuele, Zanghi, A., Gallo, A., Avolio, C., Capuano, R., Lucchini, M., Petracca, M., Bonavita, S., Lanzillo, R., Ferraro, D., Curti, E., Buccafusca, M., Callari, G., Barone, S., Pontillo, G., Abbadessa, G., Di Francescantonio, V., Signoriello, E., Lus, G., Sola, P., Granella, F., Valentino, P., Mirabella, M., Patti, F., and D'Amico, E.
Subjects: 0301 basic medicine, Male, Immunosuppressive Agent, 0302 clinical medicine, Natalizumab, Immunologic Factor, Risk Factors, Retrospective Studie, Pharmacology (medical), Prospective Studies, Disease activity, Ocrelizumab, Drug Substitution, Progressive multifocal leukoencephalopathy, Leukoencephalopathy, Progressive Multifocal, Settore MED/26 - NEUROLOGIA, Original Article, Rituximab, Female, Immunosuppressive Agents, medicine.drug, Human, Adult, medicine.medical_specialty, Adolescent, Lower risk, Antibodies, Monoclonal, Humanized, Cladribine, Exit strategy, Follow-Up Studie, 03 medical and health sciences, Young Adult, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, Post-hoc analysis, medicine, Humans, Immunologic Factors, Retrospective Studies, Pharmacology, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Risk Factor, medicine.disease, Prospective Studie, 030104 developmental biology, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: The main aim of the study is to evaluate the efficacy and safety profile of ocrelizumab (OCR), rituximab (RTX), and cladribine (CLA), employed as natalizumab (NTZ) exit strategies in relapsing–remitting multiple sclerosis (RRMS) patients at high-risk for progressive multifocal leukoencephalopathy (PML). This is a multicentre, retrospective, real-world study on consecutive RRMS patients from eleven tertiary Italian MS centres, who switched from NTZ to OCR, RTX, and CLA from January 1st, 2019, to December 31st, 2019. The primary study outcomes were the annualized relapse rate (ARR) and magnetic resonance imaging (MRI) outcome. Treatment effects were estimated by the inverse probability treatment weighting (IPTW), based on propensity-score (PS) approach. Additional endpoint included confirmed disability progression (CDP) as measured by Expanded Disability Status Scale and adverse events (AEs). Patients satisfying predefined inclusion and exclusion criteria were 120; 64 switched to OCR, 36 to RTX, and 20 to CLA. Patients from the 3 groups did not show differences for baseline characteristics, also after post hoc analysis. The IPTW PS-adjusted models revealed that patients on OCR had a lower risk for ARR than patients on CLA (ExpBOCR0.485, CI 95% 0.264–0.893,p = 0.020). This result was confirmed also for 12-month MRI activity (ExpBOCR0.248 CI 95% 0.065–0.948,p = 0.042). No differences were found in other pairwise comparisons (OCR vs RTX and RTX vs CLA) for the investigated outcomes. AEs were similar among the 3 groups. Anti-CD20 drugs were revealed to be effective and safe options as NTZ exit strategies. All investigated DMTs showed a good safety profile.
Published: 2021

28. Italian cohort of Lafora disease: Clinical features, disease evolution, and genotype-phenotype correlations

Author: Antonella Riva, Pasquale Striano, Paolo Tinuper, Roberto Michelucci, Marcello Scala, Silvana Franceschetti, Giuseppe d'Orsi, Berge A. Minassian, Angela Pistorio, Maria Teresa Di Claudio, Alfredo D'Aniello, Pierangelo Veggiotti, Carlo Avolio, Carla Marini, Maurizio Elia, Vito Sofia, Elena Freri, Maria Tappatà, Adriana Magaudda, Vittoria Taramasso, Antonino Romeo, Francesca Bisulli, Federico Zara, Giancarlo Di Gennaro, Amedeo Bianchi, Cinzia Costa, Carlo Minetti, Alessandro Orsini, Edoardo Ferlazzo, Salvatore Striano, Laura Canafoglia, Elena Gennaro, Riva A., Orsini A., Scala M., Taramasso V., Canafoglia L., d'Orsi G., Di Claudio M.T., Avolio C., D'Aniello A., Elia M., Franceschetti S., Di Gennaro G., Bisulli F., Tinuper P., Tappata M., Romeo A., Freri E., Marini C., Costa C., Sofia V., Ferlazzo E., Magaudda A., Veggiotti P., Gennaro E., Pistorio A., Minetti C., Bianchi A., Striano S., Michelucci R., Zara F., Minassian B.A., and Striano P.
Subjects: Adult, Ubiquitin-Protein Ligase, medicine.medical_specialty, Adolescent, Ubiquitin-Protein Ligases, EPM2A, EPM2B, Genetic Association Studie, medicine.disease_cause, Lafora disease, Article, 03 medical and health sciences, Epilepsy, Young Adult, 0302 clinical medicine, Progressive myoclonu, Internal medicine, medicine, Humans, Non-Receptor, 030212 general & internal medicine, Young adult, Neurodegeneration, Child, Genetic Association Studies, Mutation, business.industry, Middle Aged, medicine.disease, Protein Tyrosine Phosphatases, Non-Receptor, Progressive myoclonus, Italy, Lafora Disease, Neurology, Cohort, Neurology (clinical), medicine.symptom, Protein Tyrosine Phosphatases, business, Laforin, Myoclonus, 030217 neurology & neurosurgery, Human
Abstract: Background Lafora disease (LD) is characterized by progressive myoclonus, refractory epilepsy, and cognitive deterioration. This complex neurodegenerative condition is caused by pathogenic variants in EPM2A/EPM2B genes, encoding two essential glycogen metabolism enzymes known as laforin and malin. Long-term follow-up data are lacking. We describe the clinical features and genetic findings of a cohort of 26 Italian patients with a long clinical follow-up. Methods Patients with EPM2A/EPM2B pathogenic variants were identified by direct gene sequencing or gene panels with targeted re-sequencing. Disease progression, motor functions, and mental performance were assessed by a simplified disability scale. Spontaneous/action myoclonus severity was scored by the Magaudda Scale. Results Age range was 12.2–46.2 years (mean:25.53 ± 9.14). Age at disease onset ranged from 10 to 22 years (mean:14.04 ± 2.62). The mean follow-up period was 11.48 ± 7.8 years. Twelve out of the 26 (46%) patients preserved walking ability and 13 (50%) maintained speech. A slower disease progression with preserved ambulation and speech after ≥4 years of follow-up was observed in 1 (11%) out of the 9 (35%) EPM2A patients and in 6 (35%) out of the 17 (65%) EPM2B patients. Follow-up was >10 years in 7 (41.2%) EPM2B individuals, including two harbouring the homozygous p.(D146N) pathogenic variant. Conclusions This study supports an overall worse disease outcome with severe deterioration of ambulation and speech in patients carrying EPM2A mutations. However, the delayed onset of disabling symptoms observed in the EPM2B subjects harbouring the p.(D146N) pathogenic variant suggests that the underlying causative variant may still influence LD severity.
Published: 2021

29. An Italian multicentre study of perampanel in progressive myoclonus epilepsies

Author: Carlo Avolio, Francesca Ragona, Giuseppina Barbella, Elena Freri, Patrizia Riguzzi, Chiara Sueri, Edoardo Ferlazzo, Paolo Tinuper, Loretta Giuliano, Davide Rossi Sebastiano, Cinzia Costa, Carlo Di Bonaventura, Elena Nardi Cesarini, Tommaso Martino, Silvana Franceschetti, Francesca Bisulli, Adriana Magaudda, Giuseppe d'Orsi, Vito Sofia, Federica Zibordi, Laura Licchetta, Laura Canafoglia, Francesca Beccaria, Martina Fanella, Antonio Gambardella, Tiziana Granata, Pasquale Striano, Umberto Aguglia, Roberto Michelucci, Elisa Visani, Canafoglia L., Barbella G., Ferlazzo E., Striano P., Magaudda A., d'Orsi G., Martino T., Avolio C., Aguglia U., Sueri C., Giuliano L., Sofia V., Zibordi F., Ragona F., Freri E., Costa C., Cesarini E.N., Fanella M., Sebastiano D.R., Riguzzi P., Gambardella A., Bonaventura C.D., Michelucci R., Granata T., Bisulli F., Licchetta L., Tinuper P., Beccaria F., Visani E., and Franceschetti S.
Subjects: Adult, Male, Myoclonus, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Pyridones, Progressive myoclonus epilepsy, EPM1, EPM2, Irritability, Perampanel, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, Epilepsy, 0302 clinical medicine, Seizures, Rating scale, Nitriles, medicine, Humans, Kufs disease, Myoclonus scale, Perampanel, Progressive myoclonus epilepsy, EPM1, EPM2, Irritability, Myoclonus scale, Aged, business.industry, Middle Aged, Myoclonic Epilepsies, Progressive, medicine.disease, Treatment Outcome, 030104 developmental biology, Neurology, chemistry, Etiology, Anticonvulsants, Female, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Perampanel (PER) is a novel anti-seizure medication useful in different types of epilepsy. We intended to assess the effectiveness of PER on cortical myoclonus and seizure frequency in patients with progressive myoclonus epilepsy (PME), using quantitative validated scales. Forty-nine patients aged 36.6 ± 15.6 years with PME of various aetiology (18 EPM1, 12 EPM2, five with sialidosis, one with Kufs disease, one with EPM7, and 12 undetermined) were enrolled between January 2017 and June 2018. PER at the dose of 2–12 mg (5.3 ± 2.5) was added to existing therapy. Myoclonus severity was assessed using a minimal myoclonus scale (MMS) in all the patients before and after 4–6 months of steady PER dose, and by means of the Unified Myoclonus Rating Scale (UMRS) in 20 patients. Logistic regression analysis was used to identify the factors potentially predicting treatment efficacy. Four patients dropped out in the first two months due to psychiatric side effects. In the remaining patients, PER reduced myoclonus severity as assessed using MMS (Wilcoxon test: p < 0.001) and UMRS (p < 0.001), with the ‘Action myoclonus’ section of the UMRS showing the greatest improvement. The patients with EPM1 or EPM1-like phenotype were more likely to improve with PER (p = 0.011). Convulsive seizures which have recurred at least monthly in 17 patients were reduced by >50%. Side effects occurred in 22/49 (44.8%) patients, the most common being irritability followed by drowsiness. PER is effective in treating myoclonus and seizures in PME patients. The frequency of psychiatric side effects suggests the need for careful patient monitoring.
Published: 2019

30. Fluctuations of MS births and UV-light exposure

Author: Freek Verheul, Guillermo Izquierdo, Helmut Butzkueven, Tatjana Petkovska-Boskova, Vincent Van Pesch, Maria Laura Saladino, Jose Antonio Cabrera-Gomez, Pierre Duquette, Maria Teresa Ferrò, Mark Slee, C Zwanikken, Paolo Gallo, Gabriella Coniglio, Mark Paine, Mg Marrosu, N. Deri, Carlo Avolio, Jeannette Lechner-Scott, Giancarlo Comi, Giorgio Giuliani, Paola Cavalla, Cavit Boz, P. Grammond, Dieter Poehlau, Cameron Shaw, Roberto Bergamaschi, Michael Barnett, Maria Trojano, Franco Granella, Joost Smolders, François Grand'Maison, Giacomo Lus, M Rutherford, Jan Damoiseaux, Maria Pia Amato, Vito Lepore, Thor Petersen, Fraser Moore, W Oleschko Arruda, Ola Engelsen, R. Hupperts, Miquel Àngel Fiol, Netherlands Institute for Neuroscience (NIN), MUMC+: DA CDL Algemeen (9), RS: NUTRIM - R4 - Gene-environment interaction, Klinische Neurowetenschappen, Verheul, F, Smolders, J, Trojano, M, Lepore, V, Zwanikken, C, Amato, Mp, Grand'Maison, F, Butzkueven, H, Marrosu, M, Duquette, P, Comi, Giancarlo, Izquierdo, G, Grammond, P, Lus, G, Petersen, T, Bergamaschi, R, Giuliani, G, Boz, C, Coniglio, G, Van Pesch, V, Lechner Scott, J, Cavalla, P, Granella, F, Avolio, C, Fiol, M, Poehlau, D, Saladino, Ml, Gallo, P, Deri, N, Oleschko Arruda, W, Paine, M, Ferro, M, Barnett, M, Cabrera Gomez, Ja, Slee, M, Moore, F, Shaw, C, Petkovska Boskova, T, Rutherford, M, Engelsen, O, Damoiseaux, J, Hupperts, R., Comi, G, and Lus, Giacomo
Subjects: Gerontology, Male, Multiple Sclerosis, Databases, Factual, Ultraviolet Rays, Population, Prevalence, Global Health, Pregnancy, Risk Factors, Ultraviolet light, Medicine, Humans, Registries, education, Sunlight, education.field_of_study, business.industry, General Medicine, Odds ratio, Seasonality, medicine.disease, Neurology, Quartile, Prenatal Exposure Delayed Effects, Cohort, World Health, Female, Neurology (clinical), Seasons, business, Demography
Abstract: BACKGROUND: Patients with multiple sclerosis (MS) are more frequently born in spring when compared to autumn. Fluctuation of UV-light has been hypothesized to drive this phenomenon. AIM: To assess the correlation between fluctuation of sunlight and birth season in persons with MS. METHODS: For this record-linkage study, we collected from the international MSBase and the Italian MS iMed-web databases the dates of birth of 11,415 patients with MS from 36 centres from 15 countries worldwide and compared these to dates of live-births from national registries. From all participating sites, we collected data on UV-light fluctuation and assessed its correlation with seasonal fluctuation in MS births. RESULTS: Compared with the reference cohort, an increased proportion of persons with MS were born in spring and a decreased proportion in autumn (odds ratio (OR) to be born in spring versus autumn = 1.158, chi(2) = 36.347, P < 0.001). There was no significantly increased fluctuation of MS births with increased quartile of ambient UV-light fluctuation (Ptrend = 0.086). CONCLUSION: Seasonal fluctuation of MS births as found in this worldwide cohort of patients with MS did not correlate with variation in seasonal fluctuation of UV-light. Most likely, it results from a complex interplay between fluctuation of sunlight, behavioural factors, other environmental factors and (epi)genetic factors.
Published: 2013

31. Monocytes P2X7 purinergic receptor is modulated by glatiramer acetate in multiple sclerosis

Author: Paolo Livrea, Maddalena Ruggieri, Alessandra Bergami, Carlo Avolio, Luigi Maria Specchio, Roberto Furlan, Mariantonietta Caragnano, Paola Tortorella, Gianvito Martino, Maria Trojano, Caragnano, M, Tortorella, P, Bergami, A, Ruggieri, M, Livrea, P, Specchio, Lm, Martino, Gianvito, Trojano, M, Furlan, R, and Avolio, C.
Subjects: Adult, Male, Agonist, medicine.medical_specialty, Purinergic P2X Receptor Antagonists, medicine.drug_class, Interleukin-1beta, Primary Cell Culture, Immunology, Monocytes, Multiple Sclerosis, Relapsing-Remitting, Antigens, CD, In vivo, Internal medicine, medicine, Humans, Immunology and Allergy, Glatiramer acetate, business.industry, Multiple sclerosis, Apyrase, Purinergic receptor, Glatiramer Acetate, Middle Aged, medicine.disease, Control subjects, In vitro, Peripheral blood, Endocrinology, Neurology, Female, Receptors, Purinergic P2X7, Neurology (clinical), Peptides, business, medicine.drug
Abstract: The aim of this study is to investigate the expression of P2X7R, IL-1beta and the ATP activity modulating ecto-apyrase CD39 on peripheral blood monocytes of MS patients and to observe the possible effects of Glatiramer Acetate (GA) on such expression. Twelve RR treatment-free MS patients were selected and peripheral blood monocytes were obtained. The expression of P2X7R, IL-1beta and CD39 on monocytes was investigated by qrt-PCR. The in vitro effects of GA on the expression of monocytes stimulated with BzATP (a potent P2X7R agonist)-were evaluated. Ten healthy donors (HDs) were similarly studied. Finally, 5 MS patients were given GA therapy and the monocytes obtained before treatment, after 3 and 12 months of GA treatment were similarly investigated. No differences were found in P2X7R, IL-1beta and CD39 expression between patients and controls. In MS Bz-ATP stimulated monocytes, GA pre-conditioning clearly downregulated P2X7R (p=0.003) but IL-1beta expression also showed a decreasing trend (p=0.07). Conversely, CD39 showed an increasing trend (p=0.07). Similar evidence was found in HDs. GA in vivo treatment induced a reduction in the expression that was clear for P2X7R and CD39 (p0.05) but only not significant for IL-1beta after 12 months of treatment. Monocytes from both MS and control subjects express P2X7R, IL-1beta and CD39, and GA seems to interfere with such expression.
Published: 2012

32. T regulatory cells are markers of disease activity in multiple sclerosis patients

Author: Diletta Di Mitri, Luca Battistini, Giovanna Borsellino, Gianvito Martino, Carlo Avolio, Giancarlo Comi, Federica Sallusto, Roberto Furlan, Vittorio Martinelli, Maria Grazia Grasso, Dacia Dalla Libera, Diego Centonze, Alessandra Bergami, Claudio Gasperini, Simona Galgani, Libera, Dd, Di Mitri, D, Bergami, A, Centonze, D, Gasperini, C, Grasso, Mg, Galgani, S, Martinelli, V, Comi, Giancarlo, Avolio, C, Martino, Gianvito, Borsellino, G, Sallusto, F, Battistini, L, and Furlan, R.
Subjects: Adult, Multiple Sclerosis, Adolescent, Immune Cells, Science, T-Lymphocytes, Inflammation, chemical and pharmacologic phenomena, Relapsing-Remitting, medicine.disease_cause, T-Lymphocytes, Regulatory, Peripheral blood mononuclear cell, Autoimmune Diseases, Autoimmunity, Multiple Sclerosis, Relapsing-Remitting, Antigen, Antigens, CD, medicine, Humans, IL-2 receptor, Longitudinal Studies, Antigens, Autoimmune disease, Multidisciplinary, T Cells, business.industry, Multiple sclerosis, FOXP3, hemic and immune systems, Forkhead Transcription Factors, Middle Aged, medicine.disease, Demyelinating Disorders, Regulatory, Acute Disease, Biological Markers, CD, Neurology, Immunology, Medicine, Clinical Immunology, Settore MED/26 - Neurologia, medicine.symptom, business, Biomarkers, Research Article
Abstract: FoxP3+ Treg cells are believed to play a role in the occurrence of autoimmunity and in the determination of clinical recurrences. Contradictory reports are, however, available describing frequency and function of Treg cells during autoimmune diseases. We examined, by both polychromatic flow cytometry, and real-time RT-PCR, several Treg markers in peripheral blood mononuclear cells from patients with multiple sclerosis (MS), an autoimmune disease affecting the central nervous system. We found that Tregs, as defined by CD25, CD39, FoxP3, CTLA4, and GITR expression, were significantly decreased in stable MS patients as compared to healthy donors, but, surprisingly, restored to normal levels during an acute clinical attack. We conclude that Treg cells are not involved in causing clinical relapses, but rather react to inflammation in the attempt to restore homeostasis.
Published: 2011

33. Serum MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios in multiple sclerosis: relationships with different magnetic resonance imaging measures of disease activity during IFN-beta-1a treatment

Author: Maddalena Ruggieri, Massimo Filippi, P. Giaquinto, Valentina Tomassini, Maria Trojano, Paolo Livrea, Sergio Stecchi, C. Pozzilli, Maria A. Rocca, Carlo Avolio, Federica Agosta, Carla Tortorella, Avolio, C, Filippi, M, Tortorella, C, Rocca, Ma, Ruggieri, M, Agosta, F, Tomassini, V, Pozzilli, C, Stecchi, S, Giaquinto, P, Livrea, P, and Trojano, M
Subjects: Pathology, medicine.medical_specialty, Multiple Sclerosis, Gadolinium, chemistry.chemical_element, mmp-2/timp-2, Blood–brain barrier, Gastroenterology, Drug Administration Schedule, Central nervous system disease, 03 medical and health sciences, 0302 clinical medicine, Degenerative disease, Adjuvants, Immunologic, Recurrence, Internal medicine, medicine, Humans, 030212 general & internal medicine, interferon beta, gadolinium triple dose, mmp-9/timp-1, mri, multiple sclerosis, Tissue Inhibitor of Metalloproteinase-2, Tissue Inhibitor of Metalloproteinase-1, medicine.diagnostic_test, business.industry, Multiple sclerosis, Interferon beta-1a, Brain, Magnetic resonance imaging, Interferon-beta, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Neurology, chemistry, Matrix Metalloproteinase 9, Blood-Brain Barrier, Disease Progression, Interstitial collagenase, Matrix Metalloproteinase 2, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Matrix metalloproteinase-9 (MMP-9) is involved in blood-brain barrier (BBB) disruption in active multiple sclerosis (MS), while MMP-2 seems to be associated with the chronic progressive phase of the disease. Recombinant interferon beta-1a (rIFNβ-1a) is effective in restoring the BBB. We studied the relationships between serum MMP-9, MMP-2, TIMP-1 and TIMP-2 and different magnetic resonance imaging (MRI) measures of disease activity in MS patients during treatment with rIFNβ-1a. Twenty-one relapsing-remitting (RR) MS patients underwent longitudinally simultaneous blood withdrawals and MRI (before and after standard dose (SD) and triple dose (TD) of gadolinium (Gd)) examinations before and during 48 weeks of rIFNβ-1a (Rebif® 22 mcg three times a week) treatment. Serum MMP-9, MMP-2, TIMP-1 and TIMP-2 were measured, MMP-9 to TIMP-1 and MMP-2 to TIMP-2 ratios were calculated and the numbers of Gd-SD, Gd-TD, new-Gd-SD, new-Gd-TD and new-T2 lesions counted. Serum MMP-9/TIMP-1 ratio (P< 0.0001), as well as the numbers of ‘active’ lesions (P ranging from 0.0004 to 0.005) decreased during treatment. Moreover, serum MMP-9/TIMP-1 ratio proved to be a good positive predictor (estimate= 0.85; P> 0.05) of the numbers of MRI Gd-TD active lesions. These data confirm that serum MMP-9/TIMP-1 ratio may be viewed as a reliable marker and may be predictive of MRI activity in RR MS.
Published: 2005

34. Ocrelizumab Extended Interval Dosing in Primary Progressive Multiple Sclerosis: An Italian Experience.

Author: Zanghì A, Ferraro D, Callari G, Valentino P, Granella F, Patti F, Lus G, Bonavita S, Moretti MC, Avolio C, and D'Amico E
Subjects: Humans, Antibodies, Monoclonal, Humanized therapeutic use, Italy, Immunologic Factors therapeutic use, Immunologic Factors adverse effects, Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive drug therapy, Multiple Sclerosis, Chronic Progressive chemically induced
Abstract: Background: The intervals between two courses of anti CD20 therapies in the COVID19 pandemic era provided the opportunity to individually delay therapy, known as extended interval dosing (EID)., Methods: We collect real-world data on patients with primary progressive MS (PPMS) treated with Ocrelizumab (OCR) during the COVID'19 pandemic. The observation period in which the standard interval dosing (SID) or EID occurred (always a maintenance cycle, 600 mg) was from January 2020 to June 2021. All patients had two infusions during the observation period. Our first aim was to compare confirmed disability progression (CDP) between SID and EID patients., Results: From a total cohort of 410 patients treated with OCR, 96 patients fulfilled the inclusion criteria. All patients received two infusions during the index window, 71 received only SID infusions whilst 25 received at least one EID infusion throughout the entire follow-up. During the entire available follow-up (median 10 months, IQR 7-11), CDP was recorded in 5 patients (3/71, 4.2% SID and 2/25, 8% EID, V-Cramer = 0.141, p-value = 0.167). EID regimen did not influence the risk of CDP during the investigated follow up., Conclusion: In our multicentre real-world cohort, the EID regimen in PPMS patients did not result in increased CDP during the available follow-up., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Published: 2024
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35. Metabolic reprogramming in inflammatory microglia indicates a potential way of targeting inflammation in Alzheimer's disease.

Author: Sangineto M, Ciarnelli M, Cassano T, Radesco A, Moola A, Bukke VN, Romano A, Villani R, Kanwal H, Capitanio N, Duda L, Avolio C, and Serviddio G
Subjects: Mice, Animals, Microglia metabolism, Mice, Transgenic, Lipopolysaccharides adverse effects, Toll-Like Receptor 4 metabolism, Inflammation genetics, Inflammation metabolism, Alzheimer Disease drug therapy, Alzheimer Disease genetics, Alzheimer Disease metabolism
Abstract: Microglia activation drives the pro-inflammatory activity in the early stages of Alzheimer's disease (AD). However, the mechanistic basis is elusive, and the hypothesis of targeting microglia to prevent AD onset is little explored. Here, we demonstrated that upon LPS exposure, microglia shift towards an energetic phenotype characterised by high glycolysis and high mitochondrial respiration with dysfunction. Although the activity of electron transport chain (ETC) complexes is boosted by LPS, this is mostly devoted to the generation of reactive oxygen species. We showed that by inhibiting succinate dehydrogenase (SDH) with dimethyl malonate (DMM), it is possible to modulate the LPS-induced metabolic rewiring, facilitating an anti-inflammatory phenotype. DMM improves mitochondrial function in a direct way and by reducing LPS-induced mitochondrial biogenesis. Moreover, the block of SDH with DMM inhibits the recruitment of hypoxia inducible-factor 1 α (HIF-1α), which mediates the induction of glycolysis and cytokine expression. Similar bioenergetic alterations were observed in the microglia isolated from AD mice (3xTg-AD), which present high levels of circulating LPS and brain toll-like receptor4 (TLR4). Moreover, this well-established model of AD was used to show a potential effect of SDH inhibition in vivo as DMM administration abrogated brain inflammation and modulated the microglia metabolic alterations of 3xTg-AD mice. The RNA-sequencing analysis from a public dataset confirmed the consistent transcription of genes encoding for ETC subunits in the microglia of AD mice (5xFAD). In conclusion, TLR4 activation promotes metabolic changes and the pro-inflammatory activity in microglia, and SDH might represent a promising therapeutic target to prevent AD development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)
Published: 2023
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36. MiRNA 106a-5p in cerebrospinal fluid as signature of early relapsing remitting multiple sclerosis: a cross sectional study.

Author: Zanghì A, Manuti V, Serviddio G, D'Amico E, and Avolio C
Subjects: Humans, Female, Adolescent, Young Adult, Adult, Middle Aged, Male, Cross-Sectional Studies, Multiple Sclerosis, Relapsing-Remitting diagnosis, Multiple Sclerosis, Relapsing-Remitting genetics, Multiple Sclerosis diagnosis, Multiple Sclerosis genetics, MicroRNAs genetics
Abstract: Background: Circulating microRNAs (MiRNAs) have been investigated for their role in fine-tuning the adaptive immune response to inflammatory factors and in Multiple Sclerosis (MS). They have been investigated as possible biomarkers for the diagnosis and prognosis of the disease., Methods: A cross sectional study conducted at the MS centre of Foggia, Italy. We enrolled patients with (1) an age between 18 and 55 years, (2) a definitive diagnosis of relapsing remitting MS (RRMS) as per the revised McDonald criteria, and (3) naïve to any disease modifying therapy (DMTs), as well as (4) patients with other neurological disorders (OND). The aim of the study was to compare the levels of expression of miRNA 21-5p, miRNA 106a-5p, miRNA 146a-5p, and miRNA223-3p in cell-free cerebrospinal fluid (CSF) in RRMS patients and OND. Investigated MiRNAs were extracted, retrotranscribed, and then assessed by real-time polymerase chain reaction assay (q-PCR). A receiver-operator characteristic (ROC) curve was used to test MiRNAs as a biomarker for diagnosing MS. A linear regression analysis was done to find any association with disease characteristics at the time of diagnosis., Results: A total cohort of 70 subjects (70% women) was analyzed. Out of them, 35 had a RRMS diagnosis. MiRNA 106a-5p (7.8 ± 3.8 vs 1.3 ± 0.9, p=0.03) had higher levels in RRMS patients when compared to OND. The ROC curve indicated that MiRNA 106a-5p could be considered as a disease biomarker with an area under the curve of 0.812 (p<.001; 95% CI 0.686-0.937). Linear regression analysis showed an association between the number of oligoclonal bands and MiRNA 106a-5p levels (B-coeff 2.6, p<.001; 95% CI 1.3-4.9)., Conclusion: We described miRNA 106a-5p as a possible signature in the CSF of RRMS patients in early phases of the disease. Further studies are needed to characterize its role in early MS as a disease biomarker., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zanghì, Manuti, Serviddio, D’Amico and Avolio.)
Published: 2023
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37. Personality Traits and Fatigue in Multiple Sclerosis: A Narrative Review.

Author: Ciancio A, Moretti MC, Natale A, Rodolico A, Signorelli MS, Petralia A, Altamura M, Bellomo A, Zanghì A, D'Amico E, Avolio C, and Concerto C
Abstract: (1) Background: Multiple sclerosis (MS) is a chronic neurodegenerative autoimmune disease. Fatigue is a prevalent and debilitating symptom that significantly impacts the quality of life of these patients. A relationship between personality traits and fatigue in MS has been hypothesized but not clearly defined. (2) Methods: A literature search was carried out from databases up to April 2023 for studies correlating personality traits and fatigue in patients suffering from MS. (3) Results: A total of ten articles was included; most of the studies depict a neuroticism-fatigue correlation; however, they were not consistent in terms of the fatigue, personality, and covariate assessments. (4) Conclusions: The clinical and methodological heterogeneity of the included studies prevented us from drawing any firm conclusion on the link between personality traits and fatigue in MS. Several models of personality and different fatigue assessments have been found. Despite this, a common pathway shows that the neuroticism trait or similar personality patterns has a role in fatigue diagnosis. This may be a useful target to improve the quality of life and enhance the modification of the disease treatment results. Further homogeneous and longitudinal studies are needed.
Published: 2023
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38. Ofatumumab and Early Immunological Cells Subset Characterization in Naïve Relapsing Multiple Sclerosis Patients: A Real-World Study.

Author: D'Amico E, Zanghì A, Fantozzi R, Centonze D, and Avolio C
Subjects: Humans, Prospective Studies, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal adverse effects, Multiple Sclerosis drug therapy
Abstract: Background: Ofatumumab (OFA) is a fully human anti-CD20 monoclonal antibody administered with a 20 mg subcutaneous monthly dosing regimen., Methods: Inclusion criteria were patients: 1) aged 18-55; 2) with a confirmed diagnosis of relapsing Multiple Sclerosis (RMS), per the revised 2010 McDonald criteria; 2) who started OFA according to Italian Medicines Agency prescription rules and within 12 months from the RMS diagnosis; 3) naïve to any disease-modifying therapy. The primary outcome was to offer an overview of cellular subsets of RMS naïve patients (time 0) and then after 4 weeks (time 1) and 12 weeks (time 2) on therapy with OFA in a real-world setting., Results: Fifteen patients were enrolled. CD3+ T cell frequencies were higher at time 1 (%80.4, SD 7.7) and time 2 (%82.6, SD 5.8) when compared to time 0 (%72.4, SD 9.8), p = .013. B naïve cells were barely detectable in the OFA group at time 1 (%0.4, SD 0.5) and 2 (%1.4, SD 2.9) when compared to time 0 (%11.5, SD 3.8), p < .001., Conclusion: The progressive and increasing use of anti-CD20 drugs imposes the need for larger, prospective, real-world, long-term studies to characterize further immunophenotypes of patients with RMS treated with OFA., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Published: 2023
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39. Development and Validation of the Digital Life Balance (DLB) Scale: A Brand-New Measure for Both Harmonic and Disharmonic Use of ICTs.

Author: Duradoni M, Serritella E, Avolio C, Arnetoli C, and Guazzini A
Abstract: The use of new technologies and information communication technology services (ICTs) has greatly increased, especially after the COVID-19 pandemic, resulting in an irrevocable change in people's work-life balance (WLB). Despite the thriving literature on the dysfunctional use of new technologies, a functional use of ICTs also seems to be possible. Inspired by the theory of psychology of harmony and referring to behavioral addiction models and substance use models, we defined the construct of digital life balance to indicate a harmonic balance between digital life and real life. In this context, the imbalance between online and offline life may reflect a dysfunctional use of ICTs and can be seen as a process of disharmonization. With this perspective in mind, the aim of this study was to develop a dedicated measuring instrument that could capture both people's balanced and unbalanced use of ICTs. Through two cross-sectional studies (Study 1= 1473 participants; Study 2 = 953 participants), we validated the scale internally and externally. In line with the literature, Digital Life Balance scores appeared to be negatively associated with addiction measures and positively associated with well-being measures. In conclusion, the Digital Life Balance (DLB) Scale appears to be a reliable (ω = 0.89) and valid instrument to investigate people's harmonic and disharmonic use of ICTs.
Published: 2022
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40. Is It Time for Ocrelizumab Extended Interval Dosing in Relapsing Remitting MS? Evidence from An Italian Multicenter Experience During the COVID-19 Pandemic.

Author: Zanghì A, Avolio C, Signoriello E, Abbadessa G, Cellerino M, Ferraro D, Messina C, Barone S, Callari G, Tsantes E, Sola P, Valentino P, Granella F, Patti F, Lus G, Bonavita S, Inglese M, and D'Amico E
Subjects: Humans, Gadolinium therapeutic use, Immunologic Factors adverse effects, Pandemics, Recurrence, COVID-19, Multiple Sclerosis drug therapy, Multiple Sclerosis, Relapsing-Remitting drug therapy
Abstract: In the COVID-19 pandemic era, safety concerns have been raised regarding the risk of severe infection following administration of ocrelizumab (OCR), a B-cell-depleting therapy. We enrolled all relapsing remitting multiple sclerosis (RRMS) patients who received maintenance doses of OCR from January 2020 to June 2021. Data were extracted in December 2021. Standard interval dosing (SID) was defined as a regular maintenance interval of OCR infusion every 6 months, whereas extended interval dosing (EID) was defined as an OCR infusion delay of at least 4 weeks. Three infusions were considered in defining SID vs. EID (infusions A, B, and C). Infusion A was the last infusion before January 2020. The primary study outcome was a comparison of disease activity during the A-C interval, which was defined as either clinical (new relapses) or radiological (new lesions on T1-gadolinium or T2-weighted magnetic resonance imaging (MRI) sequences). Second, we aimed to assess confirmed disability progression (CDP). A total cohort of 278 patients (174 on SID and 104 on EID) was enrolled. Patients who received OCR on EID had a longer disease duration and a higher rate of vaccination against severe acute respiratory syndrome-coronavirus 2 (p < 0.05). EID was associated with an increased risk of MRI activity during the A-C interval (OR 5.373, 95% CI 1.203-24.001, p = 0.028). Being on SID or EID did not influence CDP (V-Cramer 0.47, p = 0.342). EID seemed to be associated with a higher risk of MRI activity in our cohort. EID needs to be carefully considered for OCR-treated patients., (© 2022. The Author(s).)
Published: 2022
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41. Editorial: Immunosenescence and multiple sclerosis: Prognostic and therapeutic implications.

Author: Zanghì A, Avolio C, Hartung HP, and D'Amico E
Abstract: Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Published: 2022
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42. Stopping Interferon Beta 1b Does Not Influence the Risk of Disability Accrual in Non-Active SPMS: Results from an Italian Real-World Study.

Author: Zanghì A, D'Amico E, Patti F, and Avolio C
Subjects: Disease Progression, Drug Substitution, Humans, Italy, Disability Evaluation, Interferon beta-1b therapeutic use, Multiple Sclerosis, Chronic Progressive complications, Multiple Sclerosis, Chronic Progressive drug therapy
Abstract: Background: No consensus exists on the possibility to stop disease modifying therapies (DMTs) in Secondary Progressive Multiple Sclerosis (SPMS)., Methods: The primary outcome was the time to reach 24-weeks confirmed Expanded Disability Status Scale (EDSS) 7.0. We enrolled all patients with a confirmed diagnosis of non-active SPMS (here, absence of clinical or radiological activity for at least 24 months before the conversion) between 1 January 2010 and 31 December 2015, at MS centers of Catania and Foggia, Italy. Patients were divided into two groups, according to the shared decision to stop DMTs (group A) or to maintain/switch to licensed interferon beta 1b for SPMS (group B). A Cox model adjusted with an inverse probability weighted propensity score (IPTW-PS) was employed., Results: A cohort of 311 patients was enrolled, 165 were in group A and 146 were in group B. Patients in the two groups were similar for baseline characteristics. The IPTW-PS adjusted Cox model for the event time to 24-weeks confirmed EDSS 7.0 did not show differences between the two groups (ExpB 0.96, CI 0.739-1.271, p = 0.819)., Conclusions: In a real-world setting, in patients with non-active SPMS, the maintaining or switching to the licensed interferon beta 1b did not reduce the risk of reaching confirmed EDSS 7.0.
Published: 2022
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43. Mesenchymal Stem Cell-Derived Extracellular Vesicles and Their Therapeutic Use in Central Nervous System Demyelinating Disorders.

Author: Allegretta C, D'Amico E, Manuti V, Avolio C, and Conese M
Subjects: Central Nervous System, Humans, Myelin-Oligodendrocyte Glycoprotein, Autoimmune Diseases metabolism, Extracellular Vesicles, Mesenchymal Stem Cells metabolism, Neuromyelitis Optica
Abstract: Autoimmune demyelinating diseases-including multiple sclerosis, neuromyelitis optica spectrum disorder, anti-myelin oligodendrocyte glycoprotein-associated disease, acute disseminated encephalomyelitis, and glial fibrillary acidic protein (GFAP)-associated meningoencephalomyelitis-are a heterogeneous group of diseases even though their common pathology is characterized by neuroinflammation, loss of myelin, and reactive astrogliosis. The lack of safe pharmacological therapies has purported the notion that cell-based treatments could be introduced to cure these patients. Among stem cells, mesenchymal stem cells (MSCs), obtained from various sources, are considered to be the ones with more interesting features in the context of demyelinating disorders, given that their secretome is fully equipped with an array of anti-inflammatory and neuroprotective molecules, such as mRNAs, miRNAs, lipids, and proteins with multiple functions. In this review, we discuss the potential of cell-free therapeutics utilizing MSC secretome-derived extracellular vesicles-and in particular exosomes-in the treatment of autoimmune demyelinating diseases, and provide an outlook for studies of their future applications.
Published: 2022
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44. Pivotal Trials in Multiple Sclerosis: Similarities Prove Not to Be Useful.

Author: Avolio C and Centonze D
Abstract: We present a commentary on the inclusion criteria and outcome measures of the major randomized trials on multiple sclerosis. A qualitative comparison of the characteristics of the enrolled patients is done. The objective is to stimulate a discussion about the need to improve research strategies. The discovery of new drugs studied without personalized criteria does not allow for useful advances in knowledge., (© 2021. The Author(s).)
Published: 2022
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45. Injectable versus oral first-line multiple sclerosis therapies: knows and unknowns from observational studies.

Author: D'Amico E, Zanghì A, and Avolio C
Abstract: Competing Interests: None
Published: 2022
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46. Predictive factors of Status Epilepticus and its recurrence in patients with adult-onset seizures: A multicenter, long follow-up cohort study.

Author: Gasparini S, Ferlazzo E, Gigli G, Pauletto G, Nilo A, Lettieri C, Bilo L, Labate A, Fortunato F, Varrasi C, Cantello R, D'Aniello A, Gennaro GD, d'Orsi G, Sabetta A, Claudio MTD, Avolio C, Dono F, Evangelista G, Cavalli SM, Cianci V, Ascoli M, Mastroianni G, Lobianco C, Neri S, Mercuri S, Mammì A, Gambardella A, Beghi E, Torino C, Tripepi G, and Aguglia U
Subjects: Adult, Cohort Studies, Female, Follow-Up Studies, Humans, Male, Retrospective Studies, Seizures epidemiology, Status Epilepticus diagnosis, Status Epilepticus epidemiology, Status Epilepticus etiology
Abstract: Purpose: Status epilepticus (SE) is associated with high morbidity and mortality. This multicenter retrospective cohort study aims to identify the factors associated with the occurrence of SE and the predictors of its recurrence in patients with adult-onset seizures., Methods: We retrospectively analyzed data of 1115 patients with seizure onset>18 years, observed from 1983 to 2020 in 7 Italian Centers (median follow-up 2.1 years). Data were collected from the databases of the Centers. Patients with SE were consecutively recruited, and patients without SE history were randomly selected in a 2:1 ratio. To assess determinants of SE, different clinical-demographic variables were evaluated and included in univariate and multivariate logistic regression model., Results: Three hundred forty-seven patients had a SE history, whereas the remaining 768 patients had either isolated seizures or epilepsy without SE history. The occurrence of SE was independently associated with increasing age at onset of disease (OR 1.02, 95% CI 1.01--1.03, p<0.001), female sex (OR 1.39, 95% CI 1.05--1.83, p=0.02) and known etiology (OR 3.58, 95% CI 2.61--4.93, p<0.001). SE recurred in 21% of patients with adult-onset SE and recurrence was associated with increasing number of anti-seizure medications taken at last follow-up (OR 1.88, 95% CI 1.31--2.71, p<0.001)., Conclusions: In patients with adult-onset seizures, SE occurrence is associated with known etiologies, advanced age and female sex. Patients with recurrent SE are likely to have a refractory epilepsy, deserving careful treatment to prevent potentially fatal events., (Copyright © 2021 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)
Published: 2021
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47. Anti-Inflammatory and Anti-Oxidant Effect of Dimethyl Fumarate in Cystic Fibrosis Bronchial Epithelial Cells.

Author: Laselva O, Allegretta C, Di Gioia S, Avolio C, and Conese M
Subjects: Epithelial Cells drug effects, Epithelial Cells metabolism, Humans, Interleukin-1beta metabolism, Oxidative Stress drug effects, Reactive Oxygen Species metabolism, Tumor Necrosis Factor-alpha metabolism, Anti-Inflammatory Agents therapeutic use, Cystic Fibrosis drug therapy, Dimethyl Fumarate therapeutic use
Abstract: Cystic Fibrosis (CF) is caused by mutations on the CF transmembrane conductance regulator (CFTR) gene and is associated with chronic infection and inflammation. Recently, it has been demonstrated that LPS-induced CFTR dysfunction in airway epithelial cells is due to an early oxidative stress. Dimethyl fumarate (DMF) is an approved anti-inflammatory and anti-oxidant drug for auto-immune and inflammatory diseases, but its role in the CF has never been investigated. In this study, we examined the effect of DMF on CF-related cytokines expression, ROS measurements and CFTR channel function. We found that DMF reduced the inflammatory response to LPS stimulation in both CF and non-CF bronchial epithelial cells, both as co-treatment and therapy, and restored LPS-mediated decrease of Trikafta™-mediated CFTR function in CF cells bearing the most common mutation, c.1521_1523delCTT (F508del). DMF also inhibited the inflammatory response induced by IL-1β/H 2 O 2 and IL-1β/TNFα, mimicking the inflammatory status of CF patients. Finally, we also demonstrated that DMF exhibited an anti-oxidant effect on CF cells after different inflammatory stimulations. Since DMF is an approved drug, it could be further investigated as a novel anti-inflammatory molecule to ameliorate lung inflammation in CF and improve the CFTR modulators efficacy.
Published: 2021
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48. Exit Strategies in Natalizumab-Treated RRMS at High Risk of Progressive Multifocal Leukoencephalopathy: a Multicentre Comparison Study.

Author: Zanghì A, Gallo A, Avolio C, Capuano R, Lucchini M, Petracca M, Bonavita S, Lanzillo R, Ferraro D, Curti E, Buccafusca M, Callari G, Barone S, Pontillo G, Abbadessa G, Di Francescantonio V, Signoriello E, Lus G, Sola P, Granella F, Valentino P, Mirabella M, Patti F, and D'Amico E
Subjects: Adolescent, Adult, Antibodies, Monoclonal, Humanized administration & dosage, Cladribine administration & dosage, Drug Substitution trends, Female, Follow-Up Studies, Humans, Immunologic Factors administration & dosage, Leukoencephalopathy, Progressive Multifocal diagnostic imaging, Leukoencephalopathy, Progressive Multifocal epidemiology, Male, Multiple Sclerosis, Relapsing-Remitting diagnostic imaging, Multiple Sclerosis, Relapsing-Remitting epidemiology, Natalizumab administration & dosage, Prospective Studies, Retrospective Studies, Risk Factors, Rituximab administration & dosage, Young Adult, Drug Substitution methods, Immunologic Factors adverse effects, Immunosuppressive Agents administration & dosage, Leukoencephalopathy, Progressive Multifocal chemically induced, Multiple Sclerosis, Relapsing-Remitting drug therapy, Natalizumab adverse effects
Abstract: The main aim of the study is to evaluate the efficacy and safety profile of ocrelizumab (OCR), rituximab (RTX), and cladribine (CLA), employed as natalizumab (NTZ) exit strategies in relapsing-remitting multiple sclerosis (RRMS) patients at high-risk for progressive multifocal leukoencephalopathy (PML). This is a multicentre, retrospective, real-world study on consecutive RRMS patients from eleven tertiary Italian MS centres, who switched from NTZ to OCR, RTX, and CLA from January 1st, 2019, to December 31st, 2019. The primary study outcomes were the annualized relapse rate (ARR) and magnetic resonance imaging (MRI) outcome. Treatment effects were estimated by the inverse probability treatment weighting (IPTW), based on propensity-score (PS) approach. Additional endpoint included confirmed disability progression (CDP) as measured by Expanded Disability Status Scale and adverse events (AEs). Patients satisfying predefined inclusion and exclusion criteria were 120; 64 switched to OCR, 36 to RTX, and 20 to CLA. Patients from the 3 groups did not show differences for baseline characteristics, also after post hoc analysis. The IPTW PS-adjusted models revealed that patients on OCR had a lower risk for ARR than patients on CLA (ExpB OCR 0.485, CI 95% 0.264-0.893, p = 0.020). This result was confirmed also for 12-month MRI activity (ExpB OCR 0.248 CI 95% 0.065-0.948, p = 0.042). No differences were found in other pairwise comparisons (OCR vs RTX and RTX vs CLA) for the investigated outcomes. AEs were similar among the 3 groups. Anti-CD20 drugs were revealed to be effective and safe options as NTZ exit strategies. All investigated DMTs showed a good safety profile., (© 2021. The Author(s).)
Published: 2021
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49. Injectable Versus Oral First-Line Disease-Modifying Therapies: Results from the Italian MS Register.

Author: D'Amico E, Zanghì A, Romeo M, Cocco E, Maniscalco GT, Brescia Morra V, Paolicelli D, De Luca G, Galgani S, Amato MP, Salemi G, Inglese M, Confalonieri PA, Lus G, Avolio C, Gallo A, Vianello M, Onofrj M, Filippi M, Trojano M, and Patti F
Subjects: Adjuvants, Immunologic administration & dosage, Administration, Oral, Adult, Cohort Studies, Female, Follow-Up Studies, Humans, Injections, Subcutaneous, Italy epidemiology, Male, Middle Aged, Multiple Sclerosis, Relapsing-Remitting diagnosis, Retrospective Studies, Glatiramer Acetate administration & dosage, Immunologic Factors administration & dosage, Interferon-beta administration & dosage, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis, Relapsing-Remitting epidemiology, Registries
Abstract: The current study aims to compare injectable and oral first-line disease-modifying therapies (DMTs) for time to first relapse, time to confirmed disability progression (CDP), and time to discontinuation using a cohort of relapsing remitting multiple sclerosis (RRMS) patients, with data extracted from the Italian MS Register. This multicenter, observational, retrospectively acquired, and propensity-adjusted cohort study utilized RRMS-naïve patients from the Italian MS Register who started either injectable or oral first-line DMTs between January 1, 2010, and December 31, 2017, to evaluate the impact on disability outcomes in patients. Enrolled patients were divided into two groups, namely the injectable group (IG) and the oral group (OG). Of a cohort of 11,416 patients, 4602 were enrolled (3919 in the IG and 683 in the OG). The IG had a higher rate of women (67.3% vs 63.4%, p < 0.05) and a lower mean age (36.1 ± 10.9 vs 38.9 ± 11.8, p < 0.001). The event time to first relapse demonstrated a lower risk in the OG (HR = 0.58; CI 95% 0.48-0.72, p < 0.001). However, no differences were found between the two groups with respect to the risk of CDP (HR = 0.94; CI 95% 0.76-1.29, p = 0.941), while a lower risk of DMT was found in the OG (HR = 0.72; CI 95% 0.58-0.88, p = 0.002) for the event time to discontinuation. Real-world data from the Italian MS Register suggests that first-line oral DMTs are associated with a lower risk of experiencing a new relapse and of therapy discontinuation compared to injectable DMTs., (© 2021. The Author(s).)
Published: 2021
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50. The presenting symptoms of Lafora Disease: An electroclinical and genetic study in five Apulian (Southern Italy) families.

Author: d'Orsi G, Lalla A, Palumbo O, Di Claudio MT, Valenzano A, Sabetta A, Lopopolo A, Muro ED, Palumbo P, Copetti M, Carella M, and Avolio C
Subjects: Adolescent, Adult, Carrier Proteins genetics, Child, Female, Genetic Testing, Humans, Italy, Male, Protein Tyrosine Phosphatases, Non-Receptor genetics, Quality of Life, Young Adult, Lafora Disease genetics, Lafora Disease physiopathology, Mutation genetics, Myoclonic Epilepsy, Juvenile genetics, Seizures genetics
Abstract: Purpose: To elucidate the presenting symptoms of Lafora Disease (LD) to differentiate it from Juvenile Myoclonic Epilepsy (JME)., Methods: We collected and evaluated the early electroclinical data of 5 unrelated Apulian (Southern Italy) LD families, 30 LD patients selected from the literature, and 30 Apulian JME patients., Results: The Apulian LD patients presented with generalised tonic-clonic and focal visual seizures, followed by myoclonic seizures and action-postural myoclonus. In these patients, EEG background slowing and occipital epileptiform abnormalities were significantly more evident than in the other groups. Genetic analysis revealed the presence of mutations in the EPM2A gene in 4 families, and in the NHLRC1 gene in the remaining family. In detail, we identified 2 different point mutations in EPM2A and only 1 in NHLRC1, and expanded the molecular spectrum of the EPM2A gene mutations reporting for the first time a patient carrier of the c.243_246del genetic variant. In the previously reported LD cases, generalised tonic-clonic and focal visual seizures and myoclonus were the most frequent symptoms, as confirmed by the first EEGs showing occipital or diffuse epileptiform abnormalities with photosensitivity in the background activity slowing. In the Apulian JME patients, myoclonus appeared earlier, usually at awakening, with diffuse epileptiform abnormalities during sleep and photosensitivity in the normal background activity. The diagnosis of JME was established much earlier than the LD one. During evolution, unlike JME patients, LD patients showed a significant resistance to drugs., Conclusions: Tonic-clonic and focal visual seizures followed by myoclonic seizures and action-postural myoclonus together with EEG background slowing with diffuse and occipital epileptiform abnormalities suggest a diagnosis of LD. An early molecular confirmation allows a better diagnosis, counselling and management of affected patients and their families, and it may be useful to improve the patients' quality of life using, when possible, emerging personalized treatments that may slow the evolution of the disease., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)
Published: 2020
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