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2. Reliability and Minimal Clinically Important Differences of FVC. Results from the Scleroderma Lung Studies (SLS-I and SLS-II)

Author

Kafaja, Suzanne, Clements, Philip J, Wilhalme, Holly, Tseng, Chi-hong, Furst, Daniel E, Kim, Grace Hyun, Goldin, Jonathan, Volkmann, Elizabeth R, Roth, Michael D, Tashkin, Donald P, Khanna, Dinesh, Arbor, Ann, Khanna, D, Angeles, Los, Clements, PJ, Tashkin, DP, Elashoff, R, Goldin, J, Roth, M, Furst, D, Bulpitt, K, Chung, W-LJ, Viasco, S, Sterz, M, Woolcock, L, Yan, X, Ho, J, Vasunilashorn, S, da Costa, I, Seibold, JR, Riley, DJ, Amorosa, JK, Hsu, VM, McCloskey, DA, Wilson, JE, Varga, J, Schraufnagel, D, Wilbur, A, Lapota, D, Arami, S, Cole-Saffold, P, Simms, R, Theodore, A, Clarke, P, Korn, J, Tobin, K, Nuite, M, Silver, R, Bolster, M, Strange, C, Schabel, S, Smith, E, Arnold, J, Caldwell, K, Bonner, M, Wise, R, Wigley, F, White, B, Hummers, L, Bohlman, M, Polito, A, Leatherman, G, Forbes, E, Daniel, M, Steen, V, Read, C, Cooper, C, Wheaton, S, Carey, A, Ortiz, A, Mayes, M, Parsley, E, Oldham, S, Filemon, T, Jordan, S, Perry, M, K. Connolly, Golden, J, Wolters, P, Webb, R, Davis, J, Antolos, C, Maynetto, C, Fessler, B, Olman, M, Sanders, C, Heck, L, Parkhill, T, Rothfield, N, Metersky, M, Cobb, R, Aberles, M, Ingenito, F, Breen, E, Mubarak, K, Granda, JL, Silva, J, Injic, Z, and Alexander, R

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Scleroderma, Lung, Clinical Research, Autoimmune Disease, Cohort Studies, Disease Progression, Female, Humans, Lung Diseases, Interstitial, Male, Middle Aged, Minimal Clinically Important Difference, Reproducibility of Results, Scleroderma, Systemic, Vital Capacity, interstitial lung disease, systemic sclerosis, FVC%, minimal clinically important differences, patient-reported outcomes, Medical and Health Sciences, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

ObjectivesTo assess the reliability and the minimal clinically important differences (MCID) for FVC% predicted in the Scleroderma Lung Study I and II.MethodsUsing data from SLS I and II (N=300), we evaluated the test-retest reliability for FVC% predicted (FVC%; screening vs. baseline) using intra-class correlation (ICC). MCID estimates at 12 months were calculated in the pooled cohort (SLS-I and II) using 2 anchors: Transition Dyspnea Index (≥change of 1.5 units for improvement and worsening, respectively) and the SF-36 Health Transition question: "Compared to one year ago, how would you rate your health in general now?", where "somewhat better" or "somewhat worse" were defined as the MCID estimates. We next assessed the association of MCID estimates for improvement and worsening of FVC% with patient reported outcomes (PROs) and computer-assisted quantitation of extent of fibrosis (QLF) and of total ILD (QILD) on HRCT.ResultsReliability of FVC%, assessed at a mean of 34 days, was 0.93 for the pooled cohort. The MCID estimates for the pooled cohort at 12 months for FVC% improvement ranged from 3.0 % to 5.3% and for worsening from -3.0% to -3.3%. FVC% improvement by ≥MCID was associated with either statistically significant or numerical improvements in some PROs, QILD, and QLF, while FVC% worsening ≥MCID was associated with statistically significant or numerical worsening of PROs, QILD, and QLF.ConclusionFVC% has acceptable test-retest reliability, and we have provided the MCID estimates for FVC% in SSc-ILD based changes at 12 months from baseline in two clinical trials. Clinical trial registration available at www.clinicaltrials.gov, IDs NCT00004563 and NCT00883129.

Published
2018

5. Protocol for a partially nested randomised controlled trial to evaluate the effectiveness of the scleroderma patient-centered intervention network COVID-19 home-isolation activities together (SPIN-CHAT) program to reduce anxiety among at-risk scleroderma patients

Author

Thombs, B.D., Kwakkenbos, L., Carrier, M.E., Bourgeault, A., Tao, L.D., Harb, S., Gagarine, M., Rice, D., Bustamante, L., Ellis, K., Duchek, D., Wu, Y., Bhandari, P.M., Neupane, D., Carboni-Jimenez, A., Henry, R.S., Krishnan, A., Sun, Y., Levis, B., He, C., Turner, K.A., Benedetti, A., Culos-Reed, N., El-Baalbaki, G., Hebblethwaite, S., Bartlett, S.J., Dyas, L., Patten, S., Varga, J., Fortune, C., Gietzen, A., Guillot, G., Lewis, N., Nielsen, K., Richard, M., Sauve, M., Welling, J., Baron, M., Furst, D.E., Gottesman, K., Malcarne, V., Mayes, M.D., Mouthon, L., Nielson, W.R., Riggs, R., Wigley, F., Assassi, S., Boutron, I., Ells, C., Ende, C. van den, Fligelstone, K., Frech, T., Godard, D., Harel, D., Hinchcliff, M., Hudson, M., Johnson, S.R., Larche, M., Leite, C., Nguyen, C., Pope, J., Portales, A., Rannou, F., Reyna, T.S.R., Schouffoer, A.A., Suarez-Almazor, M.E., Agard, C., Albert, A., Andre, M., Arsenault, G., Benzidia, I., Bernstein, E.J., Berthier, S., Bissonnette, L., Boire, G., Bruns, A., Carreira, P., Casadevall, M., Chaigne, B., Chung, L., Cohen, P., Correia, C., Dagenais, P., Denton, C., Domsic, R., Dubois, S., Dunne, J.V., Dunogue, B., Fare, R., Farge-Bancel, D., Fortin, P.R., Gill, A., Gordon, J., Granel-Rey, B., Gyger, G., Hachulla, E., Hatron, P.Y., Herrick, A.L., Hij, A., Hoa, S., Ikic, A., Jones, N., Fernandes, A.J.D., Kafaja, S., Khalidi, N., Lambert, M., Launay, D., Liang, P., Maillard, H., Maltez, N., Manning, J., Marie, I., Martin, M., Martin, T., Masetto, A., Maurier, F., Mekinian, A., Melchor, S., Nikpour, M., Olagne, L., Poindron, V., Proudman, S., Regent, A., Riviere, S., Robinson, D., Rodriguez, E., Roux, S., Smets, P., Smith, D., Sobanski, V., Spiera, R., Steen, V., Stevens, W., Sutton, E., Terrier, B., Thorne, C., Wilcox, P., Ayala, M.C., Ostbo, N., Scleroderma Patient-ctr Interventi, and SPIN Investigators

Subjects
Coronavirus, COVID-19, Systemic sclerosis, Mental health, Anxiety, RCT, Trial, Scleroderma
Abstract

Objective: Contagious disease outbreaks and related restrictions can lead to negative psychological outcomes, particularly in vulnerable populations at risk due to pre-existing medical conditions. No randomised controlled trials (RCTs) have tested interventions to reduce mental health consequences of contagious disease outbreaks. The primary objective of the Scleroderma Patient-centered Intervention Network COVID-19 Home-isolation Activities Together (SPIN-CHAT) Trial is to evaluate the effect of a videoconference-based program on symptoms of anxiety. Secondary objectives include evaluating effects on symptoms of depression, stress, loneliness, boredom, physical activity, and social interaction.Methods: The SPIN-CHAT Trial is a pragmatic RCT that will be conducted using the SPIN-COVID-19 Cohort, a sub-cohort of the SPIN Cohort. Eligible participants will be SPIN-COVID-19 Cohort participants without a positive COVID-19 test, with at least mild anxiety (PROMIS Anxiety 4a v1.0 T-score >= 55), not working from home, and not receiving current counselling or psychotherapy. We will randomly assign 162 participants to intervention groups of 7 to 10 participants each or waitlist control. We will use a partially nested RCT design to reflect dependence between individuals in training groups but not in the waitlist control. The SPIN-CHAT Program includes activity engagement, education on strategies to support mental health, and mutual participant support. Intervention participants will receive the 4-week (3 sessions per week) SPIN-CHAT Program via video-conference. The primary outcome is PROMIS Anxiety 4a score immediately post-intervention.Ethics and dissemination: The SPIN-CHAT Trial will test whether a brief videoconference-based intervention will improve mental health outcomes among at-risk individuals during contagious disease outbreak.

Published
2020

6. Protocol for a partially nested randomised controlled trial to evaluate the effectiveness of the scleroderma patient-centered intervention network COVID-19 home-isolation activities together (SPIN-CHAT) program to reduce anxiety among at-risk scleroderma patients

Author

Thombs, BD, Kwakkenbos, L, Carrier, M-E, Bourgeault, A, Tao, L, Harb, S, Gagarine, M, Rice, D, Bustamante, L, Ellis, K, Duchek, D, Wu, Y, Bhandari, PM, Neupane, D, Carboni-Jimenez, A, Henry, RS, Krishnan, A, Sun, Y, Levis, B, He, C, Turner, KA, Benedetti, A, Culos-Reed, N, El-Baalbaki, G, Hebblethwaite, S, Bartlett, SJ, Dyas, L, Patten, S, Varga, J, Fortune, C, Gietzen, A, Guillot, G, Lewis, N, Nielsen, K, Richard, M, Sauve, M, Welling, J, Baron, M, Furst, DE, Gottesman, K, Malcarne, V, Mayes, MD, Mouthon, L, Nielson, WR, Riggs, R, Wigley, F, Assassi, S, Boutron, I, Ells, C, van den Ende, C, Fligelstone, K, Frech, T, Godard, D, Harel, D, Hinchcliff, M, Hudson, M, Johnson, SR, Larche, M, Leite, C, Nguyen, C, Pope, J, Portales, A, Rannou, F, Rodriguez Reyna, TS, Schouffoer, AA, Suarez-Almazor, ME, Agard, C, Albert, A, Andre, M, Arsenault, G, Benzidia, I, Bernstein, EJ, Berthier, S, Bissonnette, L, Boire, G, Bruns, A, Carreira, P, Casadevall, M, Chaigne, B, Chung, L, Cohen, P, Correia, C, Dagenais, P, Denton, C, Domsic, R, Dubois, S, Dunne, J, Dunogue, B, Fare, R, Farge-Bancel, D, Fortin, PR, Gill, A, Gordon, J, Granel-Rey, B, Gyger, G, Hachulla, E, Hatron, P-Y, Herrick, AL, Hij, A, Hoa, S, Ikic, A, Jones, N, Fernandes, AJDB, Kafaja, S, Khalidi, N, Lambert, M, Launay, D, Liang, P, Maillard, H, Maltez, N, Manning, J, Marie, I, Martin, M, Martin, T, Masetto, A, Maurier, F, Mekinian, A, Melchor, S, Nikpour, M, Olagne, L, Poindron, V, Proudman, S, Regent, A, Riviere, S, Robinson, D, Rodriguez, E, Roux, S, Smets, P, Smith, D, Sobanski, V, Spiera, R, Steen, V, Stevens, W, Sutton, E, Terrier, B, Thorne, C, Wilcox, P, Ayala, MC, Ostbo, N, Thombs, BD, Kwakkenbos, L, Carrier, M-E, Bourgeault, A, Tao, L, Harb, S, Gagarine, M, Rice, D, Bustamante, L, Ellis, K, Duchek, D, Wu, Y, Bhandari, PM, Neupane, D, Carboni-Jimenez, A, Henry, RS, Krishnan, A, Sun, Y, Levis, B, He, C, Turner, KA, Benedetti, A, Culos-Reed, N, El-Baalbaki, G, Hebblethwaite, S, Bartlett, SJ, Dyas, L, Patten, S, Varga, J, Fortune, C, Gietzen, A, Guillot, G, Lewis, N, Nielsen, K, Richard, M, Sauve, M, Welling, J, Baron, M, Furst, DE, Gottesman, K, Malcarne, V, Mayes, MD, Mouthon, L, Nielson, WR, Riggs, R, Wigley, F, Assassi, S, Boutron, I, Ells, C, van den Ende, C, Fligelstone, K, Frech, T, Godard, D, Harel, D, Hinchcliff, M, Hudson, M, Johnson, SR, Larche, M, Leite, C, Nguyen, C, Pope, J, Portales, A, Rannou, F, Rodriguez Reyna, TS, Schouffoer, AA, Suarez-Almazor, ME, Agard, C, Albert, A, Andre, M, Arsenault, G, Benzidia, I, Bernstein, EJ, Berthier, S, Bissonnette, L, Boire, G, Bruns, A, Carreira, P, Casadevall, M, Chaigne, B, Chung, L, Cohen, P, Correia, C, Dagenais, P, Denton, C, Domsic, R, Dubois, S, Dunne, J, Dunogue, B, Fare, R, Farge-Bancel, D, Fortin, PR, Gill, A, Gordon, J, Granel-Rey, B, Gyger, G, Hachulla, E, Hatron, P-Y, Herrick, AL, Hij, A, Hoa, S, Ikic, A, Jones, N, Fernandes, AJDB, Kafaja, S, Khalidi, N, Lambert, M, Launay, D, Liang, P, Maillard, H, Maltez, N, Manning, J, Marie, I, Martin, M, Martin, T, Masetto, A, Maurier, F, Mekinian, A, Melchor, S, Nikpour, M, Olagne, L, Poindron, V, Proudman, S, Regent, A, Riviere, S, Robinson, D, Rodriguez, E, Roux, S, Smets, P, Smith, D, Sobanski, V, Spiera, R, Steen, V, Stevens, W, Sutton, E, Terrier, B, Thorne, C, Wilcox, P, Ayala, MC, and Ostbo, N

Abstract

Objective Contagious disease outbreaks and related restrictions can lead to negative psychological outcomes, particularly in vulnerable populations at risk due to pre-existing medical conditions. No randomised controlled trials (RCTs) have tested interventions to reduce mental health consequences of contagious disease outbreaks. The primary objective of the Scleroderma Patient-centered Intervention Network COVID-19 Home-isolation Activities Together (SPIN-CHAT) Trial is to evaluate the effect of a videoconference-based program on symptoms of anxiety. Secondary objectives include evaluating effects on symptoms of depression, stress, loneliness, boredom, physical activity, and social interaction.

Published
2020

7. Shortening patient-reported outcome measures through optimal test assembly: Application to the Social Appearance Anxiety Scale in the Scleroderma Patient-centered Intervention Network Cohort

Author

Harel, D., Mills, S.D., Kwakkenbos, L., Carrier, M.E., Nielsen, K., Portales, A., Bartlett, S.J., Malcarne, V.L., Thombs, B.D., Baron, M., Furst, D.E., Gottesman, K., Mayes, M.D., Mouthon, L., Nielson, W.R., Riggs, R., Sauve, M., Wigley, F., Assassi, S., Boutron, I., Maia, A.C., El-Baalbaki, G., Ells, C., Ende, C. van den, Fligelstone, K., Fortune, C., Frech, T., Godard, D., Hudson, M., Impens, A., Jang, Y., Johnson, S.R., Kennedy, A.T., Korner, A., Larche, M., Leite, C., Marra, C., Pope, J., Reyna, T.S.R., Schouffoer, A.A., Steele, R.J., Suarez-Almazor, M.E., Welling, J., Wong-Rieger, D., Agard, C., Albert, A., Andre, M., Arsenault, G., Benmostefa, N., Benzidia, I., Berthier, S., Bissonnette, L., Boire, G., Bruns, A., Carreira, P., Casadevall, M., Chaigne, B., Chung, L., Cohen, P., Dagenais, P., Denton, C., Domsic, R., Dubois, S., Dunne, J.V., Dunogue, B., Esquinca, A., Fare, R., Farge-Bancel, D., Fortin, P.R., Gill, A., Gordon, J., Granel-Rey, B., Grange, C., Gyger, G., Hachulla, E., Hatron, P.Y., Herrick, A.L., Hij, A., Hinchcliff, M., Ikic, A., Jones, N., Fernandes, A.J.D., Kafaja, S., Khalidi, N., Korman, B., Launay, D., Liang, P., London, J., Luna, D., Maillard, H., Manning, J., Martin, M., Martin, T., Masetto, A., Maurier, F., Mekinian, A., Melchor, S., Nikpour, M., Paule, R., Proudman, S., Regent, A., Riviere, S., Robinson, D., Rodriguez, E., Roux, S., Smets, P., Smith, D., Sobanski, V., Spiera, R., Steen, V., Stevens, W., Sutton, E., Terrier, B., Thorne, C., Varga, J., Wilcox, P., Wilson, M., Cumin, J., Fox, R.S., Gholizadeh, S., Jewett, L.R., Levis, B., Pepin, M.R., Turner, K.A., Lambert, M., and SPIN Investigators

Subjects
Adult, Male, medicine.medical_specialty, systemic sclerosis, Concurrent validity, Anxiety, Fear of negative evaluation, Cohort Studies, Experimental Psychopathology and Treatment, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Cronbach's alpha, medicine, Humans, Patient Reported Outcome Measures, optimal test assembly, 030212 general & internal medicine, Aged, Aged, 80 and over, Scleroderma, Systemic, business.industry, Research, short form, Social anxiety, Reproducibility of Results, generalized partial credit model, General Medicine, Middle Aged, stomatognathic diseases, Cross-Sectional Studies, Convergent validity, patient reported outcome measure, Physical Appearance, Body, Physical therapy, Female, Patient-reported outcome, medicine.symptom, business, 030217 neurology & neurosurgery, Cohort study
Abstract

ObjectivesThe Social Appearance Anxiety Scale (SAAS) is a 16-item measure that assesses social anxiety in situations where appearance is evaluated. The objective was to use optimal test assembly (OTA) methods to develop and validate a short-form SAAS based on objective and reproducible criteria.DesignThis study was a cross-sectional analysis of baseline data from adults enrolled in the Scleroderma Patient-centered Intervention Network (SPIN) Cohort.SettingAdults in the SPIN Cohort in the present study were enrolled at 28 centres in Canada, the USA and the UK.ParticipantsThe SAAS was administered to 926 adults with scleroderma.Primary and secondary measuresThe SAAS, Brief Fear of Negative Evaluation II (BFNE II), Brief Satisfaction with Appearance Scale (Brief-SWAP), Patient Health Questionnaire-8 (PHQ8) and Social Interaction Anxiety Scale-6 (SIAS-6) were collected, as well as demographic characteristics.ResultsOTA methods identified a maximally informative shortened version for each possible form length between 1 and 15 items. The final shortened version was selected based on prespecified criteria for reliability, concurrent validity and statistically equivalent convergent validity with the BFNE II scale. A five-item short version was selected (SAAS-5). The SAAS-5 had a Cronbach’s α of 0.95 and had high concurrent validity with the full-length form (r=0.97). The correlation of the SAAS-5 with the BFNE II was 0.66, which was statistically equivalent to that of the full-length form. Furthermore, the correlation of the SAAS-5 with the two subscales of the Brief-SWAP, and the SIAS-6, were statistically equivalent to that of the full-length form.ConclusionsOTA was an efficient method for shortening the full-length SAAS to create the SAAS-5.

Published
2019

8. Update of EULAR recommendations for the treatment of systemic sclerosis

Author

Kowal-Bielecka O., Fransen J., Avouac J., Becker M., Kulak A., Allanore Y., Distler O., Clements P., Cutolo M., Czirjak L., Damjanov N., Del Galdo F., Denton C. P., Distler J. H. W., Foeldvari I., Figelstone K., Frerix M., Furst D. E., Guiducci S., Hunzelmann N., Khanna D., Matucci-Cerinic M., Herrick A. L., Van Den Hoogen F., Van Laar J. M., Riemekasten G., Silver R., Smith V., Sulli A., Tarner I., Tyndall A., Welling J., Wigley F., Valentini G., Walker U. A., Zulian F., Muller-Ladner U., Daikeler T., Lanciano E., Becvar R., Tomcik M., Gindzienska-Sieskiewicz E., Cuomo G., Iudici M., Rednic S., Vlachoyiannopoulos P. G., Caporali R., Carreira P. E., Novak S., Minier T., Kucharz E. J., Gabrielli A., Moroncini G., Airo' P., Hesselstrand R., Martinovic D., Radic M., Marasovic-Krstulovic D., Braun-Moscovici Y., Balbir-Gurman A., Lo Monaco A., Caramaschi P., Morovic-Vergles J., Henes J., Ortiz Santamaria V., Heitmann S., Krasowska D., Seidel M. F., Hasler P., Pereira Da Silva J. A., Salvador M. J., Stamenkovic B., Stankovic A., Tikly M., Ananieva L. P., Beretta L., Szucs G., Szamosi S., de la Puente Bujidos C., Midtvedt O., Hoffmann-Vold A. -M., Launay D., Hachulla E., Riccieri V., Ionescu R., Opris D., Mihai C., Herrgott I., Beyer C., Ingegnoli F., von Muhlen C. A., Alegre-Sancho J. J., Beltran-Catalan E., Aringer M., Fantana J., Leuchten N., Tausche A. -K., De Langhe E., Vanthuyne M., Anic B., Baresic M., Mayer M., Uprus M., Otsa K., Yavuz S., Granel B., Azevedo V. F., Muller C., Jimenez S. A., Popa S., Agachi S., Zenone T., Stebbings S., Dockerty J., Vacca A., Schollum J., Veale D. J., Toloza S., Xu D., Olas J., Rosato E., Foti R., Adler S., Dan D., Wiesik-Szewczyk E., Olesinska M., Kayser C., Fathi N., de la Pena Lefebvre P. G., Imbert B., Kowal-Bielecka, O., Fransen, J., Avouac, J., Becker, M., Kulak, A., Allanore, Y., Distler, O., Clements, P., Cutolo, M., Czirjak, L., Damjanov, N., Del Galdo, F., Denton, C. P., Distler, J. H. W., Foeldvari, I., Figelstone, K., Frerix, M., Furst, D. E., Guiducci, S., Hunzelmann, N., Khanna, D., Matucci-Cerinic, M., Herrick, A. L., Van Den Hoogen, F., Van Laar, J. M., Riemekasten, G., Silver, R., Smith, V., Sulli, A., Tarner, I., Tyndall, A., Welling, J., Wigley, F., Valentini, G., Walker, U. A., Zulian, F., Muller-Ladner, U., Daikeler, T., Lanciano, E., Becvar, R., Tomcik, M., Gindzienska-Sieskiewicz, E., Cuomo, G., Iudici, M., Rednic, S., Vlachoyiannopoulos, P. G., Caporali, R., Carreira, P. E., Novak, S., Minier, T., Kucharz, E. J., Gabrielli, A., Moroncini, G., Airo', P., Hesselstrand, R., Martinovic, D., Radic, M., Marasovic-Krstulovic, D., Braun-Moscovici, Y., Balbir-Gurman, A., Lo Monaco, A., Caramaschi, P., Morovic-Vergles, J., Henes, J., Ortiz Santamaria, V., Heitmann, S., Krasowska, D., Seidel, M. F., Hasler, P., Pereira Da Silva, J. A., Salvador, M. J., Stamenkovic, B., Stankovic, A., Tikly, M., Ananieva, L. P., Beretta, L., Szucs, G., Szamosi, S., de la Puente Bujidos, C., Midtvedt, O., Hoffmann-Vold, A. -M., Launay, D., Hachulla, E., Riccieri, V., Ionescu, R., Opris, D., Mihai, C., Herrgott, I., Beyer, C., Ingegnoli, F., von Muhlen, C. A., Alegre-Sancho, J. J., Beltran-Catalan, E., Aringer, M., Fantana, J., Leuchten, N., Tausche, A. -K., De Langhe, E., Vanthuyne, M., Anic, B., Baresic, M., Mayer, M., Uprus, M., Otsa, K., Yavuz, S., Granel, B., Azevedo, V. F., Muller, C., Jimenez, S. A., Popa, S., Agachi, S., Zenone, T., Stebbings, S., Dockerty, J., Vacca, A., Schollum, J., Veale, D. J., Toloza, S., Xu, D., Olas, J., Rosato, E., Foti, R., Adler, S., Dan, D., Wiesik-Szewczyk, E., Olesinska, M., Kayser, C., Fathi, N., de la Pena Lefebvre, P. G., Imbert, B., UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (MGD) Service de rhumatologie, Kowal Bielecka, Otylia, Fransen, Jaap, Avouac, Jerome, Becker, Mike, Kulak, Agnieszka, Allanore, Yannick, Distler, Oliver, Clements, Philip, Cutolo, Maurizio, Czirjak, Laszlo, Damjanov, Nemanja, del Galdo, Francesco, Denton, Christopher P., Distler, Jörg H. W., Foeldvari, Ivan, Figelstone, Kim, Frerix, Marc, Furst, Daniel E., Guiducci, Serena, Hunzelmann, Nicola, Khanna, Dinesh, Matucci Cerinic, Marco, Herrick, Ariane L., van den Hoogen, Frank, van Laar, Jacob M., Riemekasten, Gabriela, Silver, Richard, Smith, Vanessa, Sulli, Alberto, Tarner, Ingo, Tyndall, Alan, Welling, Joep, Wigley, Frederic, Valentini, Gabriele, Walker, Ulrich A., Zulian, Francesco, Müller Ladner, Ulf, Daikeler, Thoma, Lanciano, Elisabetta, Becvã¡r, Radim, Tomcik, Michal, Gindzienska Sieskiewicz, Ewa, Iudici, Michele, Rednic, Simona, Vlachoyiannopoulos, Panayiotis G., Caporali, Roberto, Carreira, Patricia E., Novak, Srdan, Minier, Tã¼nde, Kucharz, Eugene J., Gabrielli, Armando, Moroncini, Gianluca, Airo, Paolo, Hesselstrand, Roger, Martinovic, Duska, Radic, Mislav, Marasovic Krstulovic, Daniela, Braun Moscovici, Yolanda, Monaco, Andrea Lo, Morovic Vergles, Jadranka, Culo, Melanie I., Henes, Jã¶rg, Santamaria, Vera Ortiz, Heitmann, Stefan, Krasowska, Dorota, Michalska Jakubus, Malgorzata, Seidel, Matthias F., Klinik III, Medizinische, Hasler, Paul, Da Silva, José A. Pereira, Salvador, Maria J., Stamenkovic, Bojana, Stankovic, Aleksandra, Tikly, Mohammed, Ananieva, Lidia P., Beretta, Lorenzo, Szucs, Gabriella, Szamosi, Szilvia, de la Puente Bujidos, Carlo, Midtvedt, Øyvind, Hoffmann Vold, Anna Maria, Launay, David, Hachulla, Eric, Riccieri, Valeria, Ionescu, Ruxandra, Opris, Daniela, Mihai, Carina, Herrgott, Ilka, Beyer, Christian, Ingegnoli, Francesca, von Mühlen, Carlos Alberto, Alegre Sancho, Juan José, Beltran Catalan, Emma, Aringer, Martin, Fantana, Julia, Leuchten, Nicolai, Tausche, Anne Kathrin, Langhe, Ellen De, Vanthuyne, Marie, Anic, Branimir, Bareå¡ic, Marko, Mayer, Miroslav, Ãœprus, Maria, Otsa, Kati, Yavuz, Sule, Granel, Brigitte, Jimenez, Sergio A., Popa, Serghei, Agachi, Svetlana, Zenone, Thierry, Stebbings, Simon, Dockerty, Joanne, Vacca, Alessandra, Schollum, Joanna, Veale, Douglas J., Toloza, Sergio, Xu, Dong, Olas, Jacek, Rosato, Edoardo, Foti, Rosario, Adler, Sabine, Dan, Diana, Wiesik Szewczyk, Ewa, Olesinska, Marzena, Kayser, Cristiane, Fathi, Nihal, de la Peña Lefebvre, Paloma García, Imbert, Bernard, and Cuomo, Giovanna

Subjects
Endothelin Receptor Antagonists, Lung Diseases, Kidney Disease, Delphi Technique, Gastrointestinal Diseases, systemic sclerosis, Scleroderma Renal Crisis, Placebo-controlled study, Angiotensin-Converting Enzyme Inhibitors, Lung Disease, Scleroderma, 0302 clinical medicine, Glucocorticoid, Phosphodiesterase 5 Inhibitor, Immunology and Allergy, skin and connective tissue diseases, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina, integumentary system, treatment, genetics and molecular biology (all), Hematopoietic Stem Cell Transplantation, cyclophosphamide, methotrexate, Pulmonary, Orvostudományok, Serotonin Uptake Inhibitor, 3. Good health, Europe, Systematic review, Hypertension, Serotonin Uptake Inhibitors, Cyclophosphamide, Methotrexate, Systemic Sclerosis, Treatment, Fingers, Fluoxetine, Glucocorticoids, Humans, Hypertension, Pulmonary, Kidney Diseases, Phosphodiesterase 5 Inhibitors, Prostaglandins I, Pyrazoles, Pyrimidines, Raynaud Disease, Rheumatology, Scleroderma, Systemic, Ulcer, Immunology, Biochemistry, Genetics and Molecular Biology (all), 030211 gastroenterology & hepatology, Endothelin Receptor Antagonist, Selective Serotonin Reuptake Inhibitors, medicine.drug, Human, medicine.medical_specialty, Gastrointestinal Disease, Klinikai orvostudományok, Riociguat, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, medicine, Finger, biochemistry, Intensive care medicine, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine, Systemic Sclerosi, 030203 arthritis & rheumatology, business.industry, Systemic, Angiotensin-Converting Enzyme Inhibitor, medicine.disease, Transplantation, Clinical research, Pyrimidine, immunology and allergy, rheumatology, immunology, Pyrazole, Physical therapy, business, Rheumatism
Abstract

The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.

Published
2017
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9. What have multicentre registries across the world taught us about the disease features of systemic sclerosis?

Author

Proudman S. M., Huq M., Stevens W., Wilson M. E., Sahhar J., Baron M., Hudson M., Pope J., Allanore Y., Distler O., Kowal-Bielecka O., Matucci-Cerinic M., H. L. Low A., Teng G. G., Law W. G., Santosa A., Nikpour M., Hill C., Lester S., Nash P., Ngian G. -S., Proudman S., Rischmueller M., Roddy J., Strickland G., Thakkar V., Walker J., Zochling J., Markland J., Robinson D., Jones N., Khalidi N., Docherty P., Kaminska E., Masetto A., Sutton E., Mathieu J. -P., Ligier S., Grodzicky T., LeClercq S., Thorne C., Gyger G., Smith D., Fortin P. R., Larche M., Abu-Hakima M., Rodriguez-Reyna T. S., Cabral A. R., Fritzler M., Avouac J., Walker U. A., Guiducci S., Riemekasten G., Air P., Hachulla E., Valentini G., Carreira P. E., Cozzi F., Gurman A. B., Braun-Moscovici Y., Damjanov N., Ananieva L. P., Scorza R., Jimenez S., Busquets J., Li M., Muller-Ladner U., Maurer B., Tyndall A., Lapadula G., Iannone F., Becvar R., Sierakowsky S., Cutolo M., Sulli A., Cuomo G., Vettori S., Rednic S., Nicoara I., Vlachoyiannopoulos P., Montecucco C., Caporali R., Novak S., Czirjak L., Varju C., Chizzolini C., Kucharz E. J., Kotulska A., Kopec-Medrek M., Widuchowska M., Rozman B., Mallia C., Coleiro B., Gabrielli A., Farge D., Hij A., Hesselstrand R., Scheja A., Wollheim F., Martinovic D., Govoni M., Lo Monaco A., Hunzelmann N., Pellerito R., Bambara L. M., Caramaschi P., Black C., Denton C., Henes J., Santamaria V. O., Heitmann S., Krasowska D., Seidel M., Oleszowsky M., Burkhardt H., Himsel A., Salvador M. J., Stamenkovic B., Stankovic A., Tikly M., Starovoytova M. N., Engelhart M., Strauss G., Nielsen H., Damgaard K., Szucs G., Mendoza A. Z., de la Puente Buijdos C., Giraldo W. A. S., Midtvedt O., Garen T., Launay D., Valesini G., Riccieri V., Ionescu R. M., Opris D., Groseanu L., Wigley F. M., Mihai C. M., Cornateanu R. S., Ionitescu R., Gherghe A. M., Gorga M., Dobrota R., Bojinca M., Schett G., Distler J. H., Meroni P., Zeni S., Mouthon L., De Keyser F., Smith V., Cantatore F. P., Corrado A., Ullman S., Iversen L., Pozzi M. R., Eyerich K., Hein R., Knott E., Szechinski J., Wiland P., Szmyrka-Kaczmarek M., Sokolik R., Morgiel E., Krummel-Lorenz B., Saar P., Aringer M., Gunther C., Anic B., Baresic M., Mayer M., Radominski S. C., de Souza Muller C., Azevedo V. F., Agachi S., Groppa L., Chiaburu L., Russu E., Zenone T., Stebbings S., Highton J., Stamp L., Chapman P., O'Donnell J., Solanki K., Doube A., Veale D., O'Rourke M., Loyo E., Rosato E., Pisarri S., Tanaseanu C. -M., Popescu M., Dumitrascu A., Tiglea I., Chirieac R., Ancuta C., Furst D. E., Kafaja S., Garcia de la Pena Lefebvre P., Rubio S. R., Exposito M. V., Sibilia J., Chatelus E., Gottenberg J. E., Chifflot H., Litinsky I., Venalis A., Butrimiene I., Venalis P., Rugiene R., Karpec D., Kerzberg E., Montoya F., Cosentino V., Low A. H. L., Teng G., Chan G., Lim A. Y. N., Ng S. C., Proudman, S. M., Huq, M., Stevens, W., Wilson, M. E., Sahhar, J., Baron, M., Hudson, M., Pope, J., Allanore, Y., Distler, O., Kowal-Bielecka, O., Matucci-Cerinic, M., H. L. Low, A., Teng, G. G., Law, W. G., Santosa, A., Nikpour, M., Hill, C., Lester, S., Nash, P., Ngian, G. -S., Proudman, S., Rischmueller, M., Roddy, J., Strickland, G., Thakkar, V., Walker, J., Zochling, J., Markland, J., Robinson, D., Jones, N., Khalidi, N., Docherty, P., Kaminska, E., Masetto, A., Sutton, E., Mathieu, J. -P., Ligier, S., Grodzicky, T., Leclercq, S., Thorne, C., Gyger, G., Smith, D., Fortin, P. R., Larche, M., Abu-Hakima, M., Rodriguez-Reyna, T. S., Cabral, A. R., Fritzler, M., Avouac, J., Walker, U. A., Guiducci, S., Riemekasten, G., Air, P., Hachulla, E., Valentini, G., Carreira, P. E., Cozzi, F., Gurman, A. B., Braun-Moscovici, Y., Damjanov, N., Ananieva, L. P., Scorza, R., Jimenez, S., Busquets, J., Li, M., Muller-Ladner, U., Maurer, B., Tyndall, A., Lapadula, G., Iannone, F., Becvar, R., Sierakowsky, S., Cutolo, M., Sulli, A., Cuomo, G., Vettori, S., Rednic, S., Nicoara, I., Vlachoyiannopoulos, P., Montecucco, C., Caporali, R., Novak, S., Czirjak, L., Varju, C., Chizzolini, C., Kucharz, E. J., Kotulska, A., Kopec-Medrek, M., Widuchowska, M., Rozman, B., Mallia, C., Coleiro, B., Gabrielli, A., Farge, D., Hij, A., Hesselstrand, R., Scheja, A., Wollheim, F., Martinovic, D., Govoni, M., Lo Monaco, A., Hunzelmann, N., Pellerito, R., Bambara, L. M., Caramaschi, P., Black, C., Denton, C., Henes, J., Santamaria, V. O., Heitmann, S., Krasowska, D., Seidel, M., Oleszowsky, M., Burkhardt, H., Himsel, A., Salvador, M. J., Stamenkovic, B., Stankovic, A., Tikly, M., Starovoytova, M. N., Engelhart, M., Strauss, G., Nielsen, H., Damgaard, K., Szucs, G., Mendoza, A. Z., de la Puente Buijdos, C., Giraldo, W. A. S., Midtvedt, O., Garen, T., Launay, D., Valesini, G., Riccieri, V., Ionescu, R. M., Opris, D., Groseanu, L., Wigley, F. M., Mihai, C. M., Cornateanu, R. S., Ionitescu, R., Gherghe, A. M., Gorga, M., Dobrota, R., Bojinca, M., Schett, G., Distler, J. H., Meroni, P., Zeni, S., Mouthon, L., De Keyser, F., Smith, V., Cantatore, F. P., Corrado, A., Ullman, S., Iversen, L., Pozzi, M. R., Eyerich, K., Hein, R., Knott, E., Szechinski, J., Wiland, P., Szmyrka-Kaczmarek, M., Sokolik, R., Morgiel, E., Krummel-Lorenz, B., Saar, P., Aringer, M., Gunther, C., Anic, B., Baresic, M., Mayer, M., Radominski, S. C., de Souza Muller, C., Azevedo, V. F., Agachi, S., Groppa, L., Chiaburu, L., Russu, E., Zenone, T., Stebbings, S., Highton, J., Stamp, L., Chapman, P., O'Donnell, J., Solanki, K., Doube, A., Veale, D., O'Rourke, M., Loyo, E., Rosato, E., Pisarri, S., Tanaseanu, C. -M., Popescu, M., Dumitrascu, A., Tiglea, I., Chirieac, R., Ancuta, C., Furst, D. E., Kafaja, S., Garcia de la Pena Lefebvre, P., Rubio, S. R., Exposito, M. V., Sibilia, J., Chatelus, E., Gottenberg, J. E., Chifflot, H., Litinsky, I., Venalis, A., Butrimiene, I., Venalis, P., Rugiene, R., Karpec, D., Kerzberg, E., Montoya, F., Cosentino, V., Low, A. H. L., Teng, G., Chan, G., Lim, A. Y. N., and Ng, S. C.

Subjects
0301 basic medicine, medicine.medical_specialty, Pediatrics, Survival, Immunology, Disease, Scleroderma, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, Immunology and Allergy, Medicine, Multicentre registrie, 030203 arthritis & rheumatology, Clinical features, Cohort study, Multicentre registries, Systemic sclerosis, business.industry, Interstitial lung disease, Autoantibody, Clinical features, medicine.disease, 030104 developmental biology, Clinical feature, Cohort, business, Cohort study, Rheumatism
Abstract

Introduction The aim of this study is to compare the clinical features, mortality and causes of death of systemic sclerosis (SSc) patients in four large multicentre registries. Methods Patients seen at least once in the Australian Scleroderma Cohort Study (ASCS) (n = 1714), the Canadian Scleroderma Research Group (CSRG) (n = 1628), the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) Network (n = 13,996) and the Systemic Sclerosis Cohort in Singapore (SCORE) (n = 500) before August 2016 were included. Clinical manifestations and survival in cohorts and disease subtypes were compared. Results Among 17,838 SSc patients, most were female (86.1%), Caucasian (84.6%) and had the limited cutaneous subtype (lcSSc) (65.0%). The anti-centromere autoantibody was the most prevalent (37.6%). More patients in SCORE had the diffuse subtype (dcSSc) (49.3%) and Scl-70 autoantibody (38.8%) (pConclusions This meta-cohort of SSc patients, the largest reported to date, provides insights into the impact of race and sex on disease manifestations and survival and confirms the early mortality in this disease.

Published
2017
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10. Progression of Interstitial Lung Disease in Systemic Sclerosis: The Importance of Pneumoproteins Krebs von den Lungen 6 and CCL18

Author

Volkmann, Elizabeth R., primary, Tashkin, Donald P., additional, Kuwana, Masataka, additional, Li, Ning, additional, Roth, Michael D., additional, Charles, Julio, additional, Hant, Faye N., additional, Bogatkevich, Galina S., additional, Akter, Tanjina, additional, Kim, Grace, additional, Goldin, Jonathan, additional, Khanna, Dinesh, additional, Clements, Philip J., additional, Furst, Daniel E., additional, Elashoff, Robert M., additional, Silver, Richard M., additional, Assassi, Shervin, additional, Theodore, A. C., additional, Simms, R. W., additional, Kissin, E., additional, Cheong, F. Y., additional, Steen, V. D., additional, Read, C. A., additional, Fridley, C., additional, Zulmatashvili, M., additional, Wise, R. A., additional, Wigley, F. M., additional, Hummers, L., additional, Leatherman, G., additional, Silver, R. M., additional, Strange, C., additional, Hant, F. N., additional, Ham, J., additional, Gibson, K., additional, Rosson, D., additional, Tashkin, D. P., additional, Elashoff, R. M., additional, Roth, M. D., additional, Clements, P. J., additional, Furst, D., additional, Volkmann, E. R., additional, Kafaja, S., additional, Kleerup, E., additional, Elashoff, D., additional, Goldin, J., additional, Ariola, E., additional, Marlis, G., additional, Mason‐Berry, J., additional, Saffold, P., additional, Rodriguez, M., additional, Guzman, L., additional, Brook, J., additional, Golden, J., additional, Connolly, M. K., additional, Eller, A., additional, Leong, D., additional, Lalosh, M., additional, Obata, J., additional, Volkov, S., additional, Schraufnagel, D., additional, Arami, S., additional, Franklin, D., additional, Varga, J., additional, Dematte, J., additional, Hinchcliff, M., additional, DeLuca, C., additional, Donnelly, H., additional, Marlin, C., additional, Riley, D. J., additional, Hsu, V. M., additional, McCloskey, D. A., additional, Phillips, K., additional, Khanna, D., additional, Martinez, F. J., additional, Schiopu, E., additional, Konkle, J., additional, Mayes, M., additional, Patel, B., additional, Assassi, S., additional, Tan, F., additional, Fischer, A., additional, Swigris, J., additional, Meehan, R., additional, Brown, K., additional, Warren, T., additional, Morrison, M., additional, Scholand, M. B., additional, Frecht, T., additional, Carey, P., additional, Villegas, M., additional, Molitor, J., additional, and Carlson, P., additional

Published
2019
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12. Update of EULAR recommendations for the treatment of systemic sclerosis

Author

Kowal-Bielecka, O. Fransen, J. Avouac, J. Becker, M. Kulak, A. Allanore, Y. Distler, O. Clements, P. Cutolo, M. Czirjak, L. Damjanov, N. Del Galdo, F. Denton, C.P. Distler, J.H.W. Foeldvari, I. Figelstone, K. Frerix, M. Furst, D.E. Guiducci, S. Hunzelmann, N. Khanna, D. Matucci-Cerinic, M. Herrick, A.L. Van Den Hoogen, F. Van Laar, J.M. Riemekasten, G. Silver, R. Smith, V. Sulli, A. Tarner, I. Tyndall, A. Welling, J. Wigley, F. Valentini, G. Walker, U.A. Zulian, F. Müller-Ladner, U. EUSTAR Coauthors Daikeler, T. Lanciano, E. Becvár, R. Tomcik, M. Gińdzieńska-Sieskiewicz, E. Cuomo, G. Iudici, M. Rednic, S. Vlachoyiannopoulos, P.G. Caporali, R. Carreira, P.E. Novak, S. Minier, T. Kucharz, E.J. Gabrielli, A. Moroncini, G. Airo', P. Hesselstrand, R. Martinovic, D. Radic, M. Marasovic-Krstulovic, D. Braun-Moscovici, Y. Balbir-Gurman, A. Lo Monaco, A. Caramaschi, P. Morovic-Vergles, J. Henes, J. Ortiz Santamaria, V. Heitmann, S. Krasowska, D. Seidel, M.F. Hasler, P. Pereira Da Silva, J.A. Salvador, M.J. Stamenkovic, B. Stankovic, A. Tikly, M. Ananieva, L.P. Beretta, L. Szucs, G. Szamosi, S. de la Puente Bujidos, C. Midtvedt, Ø. Hoffmann-Vold, A.-M. Launay, D. Hachulla, E. Riccieri, V. Ionescu, R. Opris, D. Mihai, C. Herrgott, I. Beyer, C. Ingegnoli, F. von Mühlen, C.A. Alegre-Sancho, J.J. Beltrán-Catalán, E. Aringer, M. Fantana, J. Leuchten, N. Tausche, A.-K. De Langhe, E. Vanthuyne, M. Anic, B. Barešic, M. Mayer, M. Üprus, M. Otsa, K. Yavuz, S. Granel, B. Azevedo, V.F. Muller, C. Jimenez, S.A. Popa, S. Agachi, S. Zenone, T. Stebbings, S. Dockerty, J. Vacca, A. Schollum, J. Veale, D.J. Toloza, S. Xu, D. Olas, J. Rosato, E. Foti, R. Adler, S. Dan, D. Wiesik-Szewczyk, E. Olesińska, M. Kayser, C. Fathi, N. de la Peña Lefebvre, P.G. Imbert, B.

Subjects
integumentary system, skin and connective tissue diseases
Abstract

The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc. © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Published
2017

13. Incidences and Risk Factors of Organ Manifestations in the Early Course of Systemic Sclerosis: A Longitudinal EUSTAR Study

Author

Jaeger, VK, Wirz, EG, Allanore, Y, Rossbach, P, Riemekasten, G, Hachulla, E, Distler, O, Airò, P, Carreira, PE, Balbir Gurman, A, Tikly, M, Vettori, S, Damjanov, N, Müller-Ladner, U, Distler, JHW, Li, M, Walker, UA, EUSTAR co-authors, Ananieva, L, Heitmann, S, Rednic, S, Riccieri, V, Szmyrka-Kaczmarek, M, Farge, D, Lapadula, G, Matucci-Cerinic, M, Guiducci, S, Hunzelmann, N, Ricci, M, Mihai, C, Veale, D, Hesselstrand, R, Mariok, E, Smith, V, Tarner, IH, Kucharz, EJ, Czirjak, L, Martinovic, D, Solanki, K, Ancuta, CM, Sibilia, J, Paola, C, Hassanien, M, Kahl, S, Wigley, F, Vanthuyne, M, Opris, D, Radominski, SC, Lo Monaco, A, Corrado, A, Koehm, M, Codullo, V, Radim, B, Loyo, E, Uprus, M, Pellerito, R, Zenone, T, Gabrielli, A, Kowal-Bielecka, O, Rozman, B, Scorza, R, Saketkoo, LA, Midtvedt, O, von Muhlen, A, Henes, J, Branimir, A, Hasler, P, Yavuz, S, Adler, S, Krummel-Lorenz, B, Posa, M, Engelhart, M, Denton, C, Krasowska, D, Garcia de la Pena Lefebvre, P, Cozzi, F, Mouthon, L, Rosato, E, Selmi, C, Sancho, JJA, Mallia, C, Limonta, M, Seidel, M, Foti, R, Stamp, L, Ullman, S, Stebbings, S, Santamaria, VO, Del Galdo, F, De Langhe, E, Mathieu, A, Sunderkotter, C, Eyerich, K, Stamenkovic, B, Novak, S, Sampaio-Barros, PD, Kayser, C, Litinsky, I, Couto, M, and Assassi, S

Subjects
integumentary system
Abstract

Objective Systemic sclerosis (SSc) is a rare and clinically heterogeneous autoimmune disorder characterised by fibrosis and microvascular obliteration of the skin and internal organs. Organ involvement mostly manifests after a variable period of the onset of Raynaud's phenomenon (RP). We aimed to map the incidence and predictors of pulmonary, cardiac, gastrointestinal (GI) and renal involvement in the early course of SSc. Methods In the EUSTAR cohort, patients with early SSc were identified as those who had a visit within the first year after RP onset. Incident SSc organ manifestations and their risk factors were assessed using Kaplan-Meier methods and Cox regression analysis. Results Of the 695 SSc patients who had a baseline visit within 1 year after RP onset, the incident non-RP manifestations (in order of frequency) were: skin sclerosis (75%) GI symptoms (71%), impaired diffusing capacity for monoxide40mmHg (14%), and renal crisis (3%). In the heart, incidence rates were highest for diastolic dysfunction, followed by conduction blocks and pericardial effusion. While the main baseline risk factor for a short timespan to develop FVC impairment was diffuse skin involvement, for PAPsys>40mmHg it was higher patient age. The main risk factors for incident cardiac manifestations were anti-topoisomerase autoantibody positivity and older age. Male sex, anti-RNA-polymerase-III positivity, and older age were risk factors associated with incident renal crisis. Conclusion In SSc patients presenting early after RP onset, approximately half of all incident organ manifestations occur within 2 years and have a simultaneous rather than a sequential onset. These findings have implications for the design of new diagnostic and therapeutic strategies aimed to ‘widen' the still very narrow ‘window of opportunity'. They may also enable physicians to counsel and manage patients presenting early in the course of SSc more accurately.

Published
2016

14. Efficacy of Mycophenolate Mofetil and Oral Cyclophosphamide on Skin Thickness: Post Hoc Analyses From Two Randomized Placebo‐Controlled Trials

Author

Namas, Rajaie, Tashkin, Donald P., Furst, Daniel E., Wilhalme, Holly, Tseng, Chi‐Hong, Roth, Michael D., Kafaja, Suzanne, Volkmann, Elizabeth, Clements, Philip J., Khanna, Dinesh, Elashoff, R., Goldin, J., Roth, M., Furst, D., Bulpitt, K., Chung, W.‐L. J., Viasco, S., Sterz, M., Woolcock, L., Yan, X., Ho, J., Vasunilashorn, S., Costa, I., Seibold, J. R., Riley, D. J., Amorosa, J. K., Hsu, V. M., McCloskey, D. A., Wilson, J. E., Varga, J., Schraufnagel, D., Wilbur, A., Lapota, D., Arami, S., Cole‐Saffold, P., Simms, R., Theodore, A., Clarke, P., Korn, J., Tobin, K., Nuite, M., Silver, R., Bolster, M., Strange, C., Schabel, S., Smith, E., Arnold, J., Caldwell, K., Bonner, M., Wise, R., Wigley, F., White, B., Hummers, L., Bohlman, M., Polito, A., Leatherman, G., Forbes, E., Daniel, M., Martin, D., Steen, V., Read, C., Cooper, C., Wheaton, S., Carey, A., Ortiz, A., Mayes, M., Parsley, E., Oldham, S., Filemon, T., Jordan, S., Perry, M., Connolly, K., Golden, J., Wolters, P., Webb, R., Davis, J., Antolos, C., Maynetto, C., Fessler, B., Olman, M., Sanders, C., Heck, L., Parkhill, T., Rothfield, N., Metersky, M., Cobb, R., Aberles, M., Ingenito, F., Breen, E., Mayes, M., Mubarak, K., Granda, J. L., Silva, J., Injic, Z., Alexander, R., Furst, D., Springmeyer, S., Kirkland, S., Molitor, J., Hinke, R., Mondt, A., Thompson, T., Rounds, S., Weinstein, M., Thompson, B., Paulus, H., Levy, S., Kissin, E., Cheong, F.Y., Marlis, G., Mason‐Berry, J., Saffold, P., Rodriguez, M., Guzman, L., Brook, J., Ibrahim, G., Largaespada, K., Fridley, C., Zulmastashvili, M., Manu, A., Moore, S., Hummers, L., Leatherman, G., Hant, F. N., Gibson, K., Morrison, M., Donnelly, H., Marlin, C., Gangar, J., McCloskey, D. A., Eller, A., Leong, D., Lalosh, M., Obata, J., Arami, S., Franklin, D., Schiopu, E., Benedict‐Blue, M., Leone, V., Shaw, J., Tan, F., Perry, M., Anderson, J., Saulino, A., Carey, P., Esplin, M., and Carlson, P.

Abstract

To assess the efficacy of mycophenolate mofetil (MMF) and cyclophosphamide (CYC) on modified Rodnan skin score (MRSS) in participants enrolled in the Scleroderma Lung Study (SLS) I and II. SLSI participants received daily oral CYCor matching placebo for 1 year, whereas SLS IIparticipants received daily MMFfor 2 years or daily oral CYCfor 1 year followed by placebo for second year. We assessed the impact of MMFand CYCon the MRSSin SLS IIover a 24‐month period. We also compared the change in MRSSin patients with diffuse cutaneous systemic sclerosis (dcSSc) assigned to CYCand MMFin SLS IIand SLSI versus placebo in SLSI over a 24‐month period using a linear mixed model. In SLS II, the baseline mean ± SD MRSSwas 14.0 ± 10.6 units for CYCand 15.3 ± 10.4 units for MMF; 58.5% were classified as dcSSc. CYCand MMFwere associated with statistically significant improvements in MRSSfrom baseline over the period of 24 months in dcSSc (P< 0.05 at each time point), but there were no differences between the 2 groups. In the dcSSc subgroup, the change in MRSSfrom baseline to all 6‐month visits was similar in SLS IIgroups (MMF,CYC, pooled cohort [MMF+ CYC]) and in the SLSI CYCgroup and showed statistically significant improvements compared to SLSI placebo at 12, 18, and 24 months (P< 0.05). In SLS II,MMFand CYCtreatment resulted in improvements in MRSSin patients with dcSSc over 24 months. In addition, MMFand CYCtreatment resulted in statistically significant improvements in MRSSin patients with dcSSc when compared with the SLSI placebo group.

Published
2018
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15. Assessment of right ventricular reserve utilizing exercise provocation in systemic sclerosis

Author

Fredrick M. Wigley, Ami A. Shah, Susan A. Mayer, Steven Hsu, Monica Mukherjee, Valentina Mercurio, Paul M. Hassoun, Laura K. Hummers, David A. Kass, Ryan J. Tedford, Stephen C. Mathai, Mukherjee, M., Mercurio, V., Hsu, S., Mayer, S. A., Mathai, S. C., Hummers, L. K., Kass, D. A., Hassoun, P. M., Wigley, F. M., Tedford, R. J., and Shah, A. A.

Subjects
medicine.medical_specialty, Supine position, Heart Ventricles, Hypertension, Pulmonary, Ventricular Dysfunction, Right, Exercise stre, Provocation test, Predictive Value of Test, Longitudinal strain, 030204 cardiovascular system & hematology, Article, Pulmonary hypertension, Heart Ventricle, Contractility, Systemic sclerosi, 03 medical and health sciences, Basal (phylogenetics), 0302 clinical medicine, Afterload, Predictive Value of Tests, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Exercise, Subclinical infection, 030203 arthritis & rheumatology, Scleroderma, Systemic, business.industry, medicine.disease, Blood pressure, Echocardiography, Ventricular Function, Right, Cardiology, Right ventricle, Cardiology and Cardiovascular Medicine, business, Human
Abstract

PURPOSE: Right ventricular (RV) capacity to adapt to increased afterload is the main determinant of outcome in pulmonary hypertension (PH), a common morbidity seen in systemic sclerosis (SSc). We hypothesized that supine bicycle echocardiography (SBE), coupled with RV longitudinal systolic strain (RVLSS), improves detection of limitations in RV reserve in SSc. METHODS: 56 SSc patients were prospectively studied during SBE with RV functional parameters compared at rest and peak stress. We further dichotomized patients based on resting RV systolic pressure (RVSP) to determine the effects of load on contractile response. RESULTS: Our pooled cohort analysis revealed reduced global RVLSS at rest (−16.2 ± 3.9%) with normal basal contractility (−25.6 ± 7.7%) and relative hypokinesis of the midventricular (−14.1 ± 6.0%) and apical (−8.9 ± 5.1%) segments. With exercise, global RVLSS increased significantly (p=0.0005), however despite normal basal contractility at rest, there was no further augmentation with exercise. Mid and apical RVLSS increased with exercise suggestive of RV contractile reserve. In patients with resting RVSP < 35 mmHg, global and segmental RVLSS increased with exercise. In patients with resting RVSP ≥35 mmHg, global and segmental RVLSS did not increase with exercise and there was evidence of exertional RV dilation. CONCLUSION: Exercise provocation in conjunction with RVLSS identified differential regional contractile response to exercise in SSc patients. We further demonstrate the effect of increased loading conditions on RV contractile response exercise. These findings suggest subclinical impairments in RV reserve in SSc that may be missed by resting noninvasive 2DE-based assessments alone.

Published
2021
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16. Distinct clinical trajectories of gastrointestinal progression among patients with systemic sclerosis.

Author

Perin J, Hughes M, Mecoli CA, Paik JJ, Gelber AC, Wigley FM, Hummers LK, Shah AA, Zeger SL, and McMahan ZH

Abstract

Objectives: Systemic sclerosis (SSc) is heterogeneous in its clinical presentation. Common manifestations cluster together, defining unique subgroups. This investigation aims to characterize gastrointestinal (GI) phenotypes and determine whether they can be distinguished by temporal progression., Methods: We examine a well-established SSc patient cohort with a modified Medsger GI severity score measured over time to determine heterogeneity in disease progression. Growth mixture models estimate each patient's phenotype and disease severity trajectory over time. We compare the characteristics of estimated phenotypes using non-parametric statistics and linear and logistic regression to compare patient characteristics between phenotypes while adjusting for disease duration., Results: We examined 2696 SSc patients with at least two Medsger GI scores, identifying four unique phenotypes. The most common phenotype (n = 2325) ("Stable") had an average score of 1 that was consistent over time. Two phenotypes were progressive ["Early Progressive" (n = 142) and "Late Progressive" (n = 115)] with an initial average score of 1. The Early Progressive group increased initially and stabilized, and the Late Progressive group worsened slowly over time. A fourth phenotype ["Early Severe GI"; (n = 114)] had an initial average Medsger GI score just below 3 with high mortality and improving GI severity over time., Conclusions: Clinically distinct GI phenotypes exist among patients with SSc. These phenotypes are not only distinguished by GI and extra-intestinal SSc clinical complications, but they are also temporally distinct. Distinct autoantibody profiles are associated strongly with more severe GI disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2024
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19. Troponin elevation independently associates with mortality in systemic sclerosis.

Author

Paik JJ, Choi DY, Mukherjee M, Hsu S, Wigley F, Shah AA, and Hummers LK

Subjects
Humans, Stroke Volume, Retrospective Studies, Cross-Sectional Studies, Ventricular Function, Left, Biomarkers, Prognosis, Troponin, Scleroderma, Systemic diagnosis, Scleroderma, Systemic complications
Abstract

Objectives: Cardiac involvement is common in systemic sclerosis (SSc), and elevated troponin may be the only sign of ongoing myocardial disease. The objective was to determine whether the presence of elevated troponin associates with unique SSc characteristics and poor outcomes., Methods: This retrospective, cross-sectional study included patients in the Johns Hopkins Scleroderma Center Research Registry with any troponin measurement in the past 10 years. Clinical data were compared between those with elevated versus normal troponin. Survival analyses including Cox proportional hazards and regression analyses were performed., Results: 272 patients with a troponin measurement were identified. 83 (31%) had elevated troponin. Compared to those with a normal troponin level, those with elevated troponin level were more likely to have the diffuse SSc subtype (p=0.005), lower left ventricular ejection fraction (57.7 ± 20% vs. 64.4 ± 17.4%, p=0.007), lower forced vital capacity percent predicted (61.1 ± 18.8% vs. 66.8 ± 20.4%, p=0.03), higher right ventricular systolic pressure (51.4 ± 20.9 vs. 43.4 ± 15.9 mmHg, p=0.001), higher Medsger muscle and heart severity scores (p≤0.001), and higher frequency of mortality (28% vs. 9.5%, p≤0.0001). Patients with elevated troponin also have a 2.16-fold (95% CI 1.01-4.63, p=0.046) increased risk of death compared to those without elevated troponin even after adjusting for age, sex, disease duration, and cardiopulmonary risk factors., Conclusions: Troponin may be a useful prognostic biomarker that may identify a subset of patients with heart disease that may warrant closer clinical investigation.

Published
2022
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20. Effect of mycophenolate mofetil dose on antibody response following initial SARS-CoV-2 vaccination in patients with systemic sclerosis.

Author

Wallwork R, Connolly CM, Shneyderman M, McMahan Z, Mecoli CA, Wigley F, Hummers LK, Shah AA, and Paik JJ

Abstract

Competing Interests: RW and CMC contributed equally. CAM reports consulting fees from Boehringer Ingelheim and payment for expert testimony from the National Vaccine Injury Compensation Program–US Department of Health and Human Services. All other authors declare no competing interests. This work was supported in part by grant numbers K23AR073927 (JJP), T32 AR048522–18 (RW), R01 AR073208 (AAS), and P30 AR070254 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases–National Institutes of Health; the Scleroderma Research Foundation; the Martha McCrory Professorship (FW); and the Johns Hopkins in Health initiative. We thank Adrianne Woods for data management.

Published
2022
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21. The Scleroderma Patient-Centered Intervention Network Self-Management Program: Protocol for a Randomized Feasibility Trial.

Author

Carrier ME, Kwakkenbos L, Nielson WR, Fedoruk C, Nielsen K, Milette K, Pope J, Frech T, Gholizadeh S, Hummers L, Johnson SR, Piotrowski P, Jewett L, Gordon J, Chung L, Bilsker D, Turner KA, Cumin J, Welling J, Fortune C, Leite C, Gottesman K, Sauve M, Rodríguez-Reyna TS, Hudson M, Larche M, van Breda W, Suarez-Almazor ME, Bartlett SJ, Malcarne VL, Mayes MD, Boutron I, Mouthon L, Wigley F, and Thombs BD

Abstract

Background: Systemic sclerosis (SSc), or scleroderma, is a rare disease that often results in significant disruptions to activities of daily living and can negatively affect physical and psychological well-being. Because there is no known cure, SSc treatment focuses on reducing symptoms and disability and improving health-related quality of life (HRQoL). Self-management programs are known to increase self-efficacy for disease management in many chronic diseases. The Scleroderma Patient-centered Intervention Network (SPIN) developed a Web-based self-management program (SPIN self-management; SPIN-SELF) to increase self-efficacy for disease management and to improve HRQoL for patients with SSc., Objective: The proposed study aims to assess the feasibility of conducting a full-scale randomized controlled trial (RCT) of the SPIN-SELF program by evaluating the trial implementation processes, required resources and management, scientific aspects, and participant acceptability and usage of the SPIN-SELF program., Methods: The SPIN-SELF feasibility trial will be conducted via the SPIN Cohort. The SPIN Cohort was developed as a framework for embedded pragmatic trials using the cohort multiple RCT design. In total, 40 English-speaking SPIN Cohort participants with low disease management self-efficacy (Self-Efficacy for Managing Chronic Disease Scale score ≤7), who have indicated interest in using a Web-based self-management program, will be randomized with a 3:2 ratio into the SPIN-SELF program or usual care for 3 months. Feasibility outcomes include trial implementation processes, required resources and management, scientific aspects, and patient acceptability and usage of the SPIN-SELF program., Results: Enrollment of the 40 participants occurred between July 5, 2019, and July 27, 2019. By November 25, 2019, data collection of trial outcomes was completed. Data analysis is underway, and results are expected to be published in 2020., Conclusions: The SPIN-SELF program is a self-help tool that may improve disease-management self-efficacy and improve HRQoL in patients with SSc. The SPIN-SELF feasibility trial will ensure that trial methodology is robust, feasible, and consistent with trial participant expectations. The results will guide adjustments that need to be implemented before undertaking a full-scale RCT of the SPIN-SELF program., International Registered Report Identifier (irrid): DERR1-10.2196/16799., (©Marie-Eve Carrier, Linda Kwakkenbos, Warren R Nielson, Claire Fedoruk, Karen Nielsen, Katherine Milette, Janet Pope, Tracy Frech, Shadi Gholizadeh, Laura Hummers, Sindhu R Johnson, Pamela Piotrowski, Lisa Jewett, Jessica Gordon, Lorinda Chung, Dan Bilsker, Kimberly A Turner, Julie Cumin, Joep Welling, Catherine Fortune, Catarina Leite, Karen Gottesman, Maureen Sauve, Tatiana S Rodríguez-Reyna, Marie Hudson, Maggie Larche, Ward van Breda, Maria E Suarez-Almazor, Susan J Bartlett, Vanessa L. Malcarne, Maureen D. Mayes, Isabelle Boutron, Luc Mouthon, Fredrick Wigley, Brett D Thombs, SPIN Investigators. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 24.04.2020.)

Published
2020
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22. Morphea and systemic sclerosis are associated with an increased risk for melanoma and nonmelanoma skin cancer.

Author

Boozalis E, Shah AA, Wigley F, Kang S, and Kwatra SG

Subjects
Comorbidity, Female, Humans, Male, Prevalence, Retrospective Studies, Risk Factors, Carcinoma, Basal Cell epidemiology, Carcinoma, Squamous Cell epidemiology, Melanoma epidemiology, Scleroderma, Localized epidemiology, Scleroderma, Systemic epidemiology, Skin Neoplasms epidemiology
Published
2019
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23. Performance of the Patient-Reported Outcomes Measurement Information System-29 in scleroderma: a Scleroderma Patient-centered Intervention Network Cohort Study.

Author

Kwakkenbos L, Thombs BD, Khanna D, Carrier ME, Baron M, Furst DE, Gottesman K, van den Hoogen F, Malcarne VL, Mayes MD, Mouthon L, Nielson WR, Poiraudeau S, Riggs R, Sauvé M, Wigley F, Hudson M, and Bartlett SJ

Subjects
Adult, Aged, Canada, Cohort Studies, Contracture etiology, Female, Gastrointestinal Diseases etiology, Humans, Joint Diseases etiology, Male, Middle Aged, Quality of Life, Reproducibility of Results, Scleroderma, Systemic complications, Surveys and Questionnaires, United Kingdom, United States, Health Status, Outcome Assessment, Health Care methods, Patient Reported Outcome Measures, Scleroderma, Systemic pathology, Severity of Illness Index
Abstract

Objective: The Patient-Reported Outcomes Measurement Information System (PROMIS)-29 assesses seven health-related quality of life domains plus pain intensity. The objective was to examine PROMIS-29v2 validity and explore clinical associations in patients with SSc., Methods: English-speaking SSc patients in the Scleroderma Patient-centered Intervention Network Cohort from 26 sites in Canada, the USA and the UK completed the PROMIS-29v2 between July 2014 and November 2015. Enrolling physicians provided medical data. To examine convergent validity, hypotheses on the direction and magnitude of correlations with legacy measures were tested. For clinical associations, t -tests were conducted for dichotomous variables and PROMIS-29v2 domain scores. Effect sizes (ESs) were labelled as small (<0.25), small to moderate (0.25-0.45), moderate (0.46-0.55), moderate to large (0.56-0.75) and large (>0.75)., Results: There were 696 patients (87% female), mean ( s . d .) disease duration 11.6 (8.7) years, 57% with limited cutaneous subtype. Validity indices were consistent with seven of nine hypotheses (| r | =0.51-0.87, P < 0.001), with minor divergence for two hypotheses. Gastrointestinal involvement was associated with significantly worse outcomes for all eight PROMIS-29v2 domains (moderate or moderate to large ES in six of eight). Presence of joint contractures was associated with significant decrements in seven domains (small or small to moderate ESs). Skin thickening, diffuse cutaneous subtype and presence of overlap syndromes were significantly associated (small or small to moderate ESs) with five or six domains., Conclusion: This study further establishes the validity of the PROMIS-29v2 in SSc and underlines the importance of gastrointestinal symptoms and joint contractures in reduced health-related quality of life., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Published
2017
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24. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial.

Author

Tashkin DP, Roth MD, Clements PJ, Furst DE, Khanna D, Kleerup EC, Goldin J, Arriola E, Volkmann ER, Kafaja S, Silver R, Steen V, Strange C, Wise R, Wigley F, Mayes M, Riley DJ, Hussain S, Assassi S, Hsu VM, Patel B, Phillips K, Martinez F, Golden J, Connolly MK, Varga J, Dematte J, Hinchcliff ME, Fischer A, Swigris J, Meehan R, Theodore A, Simms R, Volkov S, Schraufnagel DE, Scholand MB, Frech T, Molitor JA, Highland K, Read CA, Fritzler MJ, Kim GHJ, Tseng CH, and Elashoff RM

Subjects
Adult, Aged, Disease Progression, Double-Blind Method, Female, Humans, Lung physiopathology, Lung Diseases, Interstitial etiology, Lung Diseases, Interstitial physiopathology, Male, Middle Aged, Respiratory Function Tests, Scleroderma, Systemic physiopathology, Treatment Outcome, Cyclophosphamide administration & dosage, Immunosuppressive Agents administration & dosage, Lung Diseases, Interstitial drug therapy, Mycophenolic Acid administration & dosage, Scleroderma, Systemic complications
Abstract

Background: 12 months of oral cyclophosphamide has been shown to alter the progression of scleroderma-related interstitial lung disease when compared with placebo. However, toxicity was a concern and without continued treatment the efficacy disappeared by 24 months. We hypothesised that a 2 year course of mycophenolate mofetil would be safer, better tolerated, and produce longer lasting improvements than cyclophosphamide., Methods: This randomised, double-blind, parallel group trial enrolled patients from 14 US medical centres with scleroderma-related interstitial lung disease meeting defined dyspnoea, pulmonary function, and high-resolution CT (HRCT) criteria. The data coordinating centre at the University of California, Los Angeles (UCLA, CA, USA), randomly assigned patients using a double-blind, double-dummy, centre-blocked design to receive either mycophenolate mofetil (target dose 1500 mg twice daily) for 24 months or oral cyclophosphamide (target dose 2·0 mg/kg per day) for 12 months followed by placebo for 12 months. Drugs were given in matching 250 mg gel capsules. The primary endpoint, change in forced vital capacity as a percentage of the predicted normal value (FVC %) over the course of 24 months, was assessed in a modified intention-to-treat analysis using an inferential joint model combining a mixed-effects model for longitudinal outcomes and a survival model to handle non-ignorable missing data. The study was registered with ClinicalTrials.gov, number NCT00883129., Findings: Between Sept 28, 2009, and Jan 14, 2013, 142 patients were randomly assigned to either mycophenolate mofetil (n=69) or cyclophosphamide (n=73). 126 patients (mycophenolate mofetil [n=63] and cyclophosphamide [n=63]) with acceptable baseline HRCT studies and at least one outcome measure were included in the primary analysis. The adjusted % predicted FVC improved from baseline to 24 months by 2·19 in the mycophenolate mofetil group (95% CI 0·53-3·84) and 2·88 in the cyclophosphamide group (1·19-4·58). The course of the % FVC did not differ significantly between the two treatment groups based on the prespecified primary analysis using a joint model (p=0·24), indicating that the trial was negative for the primary endpoint. However, in a post-hoc analysis of the primary endpoint, the within-treatment change from baseline to 24 months derived from the joint model showed that the % FVC improved significantly in both the mycophenolate mofetil and cyclophosphamide groups. 16 (11%) patients died (five [7%] mycophenolate mofetil and 11 [15%] cyclophosphamide), with most due to progressive interstitial lung disease. Leucopenia (30 patients vs four patients) and thrombocytopenia (four vs zero) occurred more often in patients given cyclophosphamide than mycophenolate mofetil. Fewer patients on mycophenolate mofetil than on cyclophosphamide prematurely withdrew from study drug (20 vs 32) or met prespecified criteria for treatment failure (zero vs two). The time to stopping treatment was shorter in the cyclophosphamide group (p=0·019)., Interpretation: Treatment of scleroderma-related interstitial lung disease with mycophenolate mofetil for 2 years or cyclophosphamide for 1 year both resulted in significant improvements in prespecified measures of lung function over the 2 year course of the study. Although mycophenolate mofetil was better tolerated and associated with less toxicity, the hypothesis that it would have greater efficacy at 24 months than cyclophosphamide was not confirmed. These findings support the potential clinical effectiveness of both cyclophosphamide and mycophenolate mofetil for progressive scleroderma-related interstitial lung disease, and the present preference for mycophenolate mofetil because of its better tolerability and toxicity profile., Funding: National Heart, Lung and Blood Institute, National Institutes of Health; with drug supply provided by Hoffmann-La Roche and Genentech., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Published
2016
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26. Antinuclear antibody-negative systemic sclerosis.

Author

Salazar GA, Assassi S, Wigley F, Hummers L, Varga J, Hinchcliff M, Khanna D, Schiopu E, Phillips K, Furst DE, Steen V, Baron M, Hudson M, Taillefer SS, Pope J, Jones N, Docherty P, Khalidi NA, Robinson D, Simms RW, Silver RM, Frech TM, Fessler BJ, Molitor JA, Fritzler MJ, Segal BM, Al-Kassab F, Perry M, Yang J, Zamanian S, Reveille JD, Arnett FC, Pedroza C, and Mayes MD

Subjects
Adult, Case-Control Studies, Female, Humans, Hypertension, Pulmonary etiology, Kidney Diseases etiology, Lung physiopathology, Malabsorption Syndromes etiology, Male, Middle Aged, Pulmonary Diffusing Capacity, Pulmonary Fibrosis etiology, Retrospective Studies, Scleroderma, Systemic complications, Scleroderma, Systemic physiopathology, Sex Factors, Skin Ulcer etiology, Telangiectasis etiology, Antibodies, Antinuclear immunology, Scleroderma, Systemic immunology
Abstract

Objective: To examine the demographic and clinical characteristics of systemic sclerosis (SSc) patients without antinuclear antibodies (ANA) compared to ANA-positive patients., Methods: SSc patients enrolled in the Scleroderma Family Registry and DNA Repository were included. Relevant demographic and clinical data were entered by participating sites or obtained by chart review. ANA and SSc-related antibodies were determined in all investigated patients using commercially available kits at our laboratories., Results: This study included 3249 patients, of whom 208 (6.4%) were ANA negative. The proportion of male patients was higher in the ANA-negative group (OR = 1.65; p = 0.008). ANA-negative patients experienced less vasculopathic manifestations of SSc. The percent predicted diffusing capacity of carbon monoxide (DLCO) was higher in ANA-negative patients (p = 0.03). Pulmonary arterial hypertension (PAH) per right heart catheterization was less common in the ANA-negative group (OR = 0.28; p = 0.03). Furthermore, patients with negative ANA had a lower prevalence of telangiectasias and digital ulcers/pits (OR = 0.59, p = 0.03 and OR = 0.38, p = 0.01, respectively). Although diffuse cutaneous involvement was more common, the modified Rodnan Skin Score (mRSS) was lower in the ANA-negative group (2.4 points lower, p = 0.05). Furthermore, they experienced more malabsorption (p = 0.05). There was no difference in the frequency of pulmonary fibrosis or scleroderma renal crisis. All-cause mortality was not different between the 2 groups (p = 0.28)., Conclusions: In conclusion, the results of this study suggest that SSc patients who are ANA negative constitute a distinct subset of SSc with less vasculopathy (less PAH, digital ulcers, and fewer telangiectasias), a greater proportion of males, and possibly, more frequent lower gastrointestinal involvement., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Published
2015
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27. Case records of the Massachusetts General Hospital. Case 8-2015. A 68-year-old man with multiple myeloma, skin tightness, arthralgias, and edema.

Author

Wigley F, Friday RP, Shepard JA, and Nazarian RM

Subjects
Aged, Arthralgia etiology, Deglutition Disorders etiology, Diagnosis, Differential, Edema etiology, Fatal Outcome, Humans, Hyperpigmentation etiology, Kidney Diseases diagnosis, Lung diagnostic imaging, Lung pathology, Male, Multiple Myeloma complications, Scleroderma, Diffuse complications, Scleroderma, Diffuse pathology, Scleromyxedema diagnosis, Tomography, X-Ray Computed, Scleroderma, Diffuse diagnosis, Skin pathology
Published
2015
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