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1. Defining remission in childhood-onset lupus: PReS-endorsed consensus definitions by an international task force

Author

Goilav, B., Goss, N., Oni, L., Marks, S.D., Smith, E.M.D., Aggarwal, A., Ainsworth, J., Al-Abadi, E., Avcin, T., Bortey, L., Burnham, J., Ciurtin, C., Hedrich, C.M., Kamphuis, S., Lambert, L., Levy, D.M., Lewandowski, L., Maxwell, N., Morand, E., Özen, S., Pain, C.E., Ravelli, A., Saad Magalhaes, C., Pilkington, C., Schonenberg-Meinema, D., Scott, C., Tullus, K., and Beresford, M.W.

Published
2024
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3. PReS-endorsed international childhood lupus T2T task force definition of childhood lupus low disease activity state (cLLDAS)

Author

Goilav, B., Marks, S., Oni, L., Smith, E.M.D., Aggarwal, A., Ainsworth, J., Al-Abadi, E., Avcin, T., Bortey, L., Burnham, J., Ciurtin, C., Hedrich, C.M., Kamphuis, S., Lambert, L., Levy, D.M., Lewandowski, L., Maxwell, N., Morand, E., Ozen, S., Pain, C.E., Ravelli, A., Saad Magalhaes, C., Pilkington, C., Schonenberg-Meinema, D., Scott, C., Tullus, K., and Beresford, M.W.

Published
2023
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4. Safety and effectiveness of abatacept in juvenile idiopathic arthritis: Results from the PRINTO/PRCSG registry

Author

Lovell, D, Tzaribachev, N, Henrickson, M, Simonini, G, Griffin, T, Alexeeva, E, Bohnsack, J, Zeft, A, Horneff, G, Vehe, R, Stanevica, V, Tarvin, S, Trachana, M, Del Rio, A, Huber, A, Kietz, D, Orban, I, Dare, J, Foeldvari, I, Quartier, P, Dominique, A, Simon, T, Martini, A, Brunner, H, Ruperto, N, Brunner, J, Fernandes, T, Appenzeller, S, Oliveira, S, Terreri, M, Minden, K, Hufnagel, M, Helling-Bakki, A, Herlin, T, Moreno, E, Anton, J, Del-Castillo, P, Udaondo, C, Penades, I, Brochard, K, Ramanan, A, Hashkes, P, Olivieri, A, Zulian, F, Montin, D, Peroni, D, Stanevicha, V, Cornejo, G, Wulffraat, N, Kamphuis, S, Gastanaga, M, Miraval, T, Oliveira-Ramos, F, Lazar, C, Nikishina, I, Sarychev, A, Chasnyk, V, Grebenkina, L, Suwairi, W, Koskova, E, Ally, M, Louw, I, Breedt, J, Ting, T, Taylor, J, Huggins, J, Dewitt, E, Grom, A, Schulert, G, Rodriguez-Smith, J, Morris, P, Sukumarain, S, Gitelman, M, Miller, M, Curran, M, Alperin, R, Ardalan, K, De Ranieri, D, Hiskey, M, Nolan, B, Chalom, B, Zelf, A, Spalding, S, Costanzo, D, Rennebohm, R, Waugaman, B, Brodus, E, Robinson, A, Panupattanapong, S, Rosenkranz, M, Cassidy, E, Torok, K, Kingsbury, D, Cartwright, V, Lasky, A, Brown, D, Reiff, A, Shaham, B, Marzan, K, Wagner-Weiner, L, Onel, K, Tesher, M, Edens, C, Moore, T, Syed, R, Pepmueller, P, Tuttle, P, Dalrymple, A, Barhula, S, Feller, L, Horwitz, M, Justice, M, Nocton, J, Olson, J, Williams, C, Versbsy, J, Co, D, Roth-Wojcicki, E, Correll, C, Binstadt, B, Hobday, P, Brueck, D, Gillispie-Taylor, M, Vora, S, O'Neil, K, Ballinger, S, Blakley, M, Klausmeier, T, Oliver, M, Stevens, B, Rodriguez, M, Go, E, Inman, C, Hersh, A, Stern, S, Woodward, A, Durkee, D, Boulva, S, James, K, Treemarcki, E, Goldsmith, D, Lvovich, S, Toib, D, Patel, J, Jerath, R, Sharma, N, Newhall, L, Carrasco, R, Moorthy, N, Boneparth, A, Quintero, A, Graham, T, Spence, S, Davis, A, Gotte, A, Mehta, J, Walters, H, Mian, Z, Parkinson, E, Hui-Yen, J, Steigerwald, K, Guzman, M, Gottlieb, B, Whitaker, C, Kelly, L, Succimarri, R, Hazel, E, Chedeville, G, Compillo, S, Leblance, C, Tucker, L, Cabral, D, Houghton, K, Guzman, J, Morishita, K, Stringer, E, Ramsey, S, Lang, B, Levy, D, Silverman, E, Schmeling, H, Johnson, N, Luca, N, Dhalla, M, Lovell D. J., Tzaribachev N., Henrickson M., Simonini G., Griffin T. A., Alexeeva E., Bohnsack J. F., Zeft A., Horneff G., Vehe R. K., Stanevica V., Tarvin S., Trachana M., Del Rio A. Q., Huber A. M., Kietz D., Orban I., Dare J., Foeldvari I., Quartier P., Dominique A., Simon T. A., Martini A., Brunner H. I., Ruperto N., Brunner J., Fernandes T., Appenzeller S., Oliveira S., Terreri M. T., Minden K., Hufnagel M., Helling-Bakki A., Herlin T., Moreno E., Anton J., Del-Castillo P. M. -., Udaondo C., Penades I. C., Brochard K., Ramanan A., Hashkes P. P., Olivieri A. N., Zulian F., Montin D., Peroni D., Stanevicha V., Cornejo G. V., Wulffraat N., Kamphuis S., Gastanaga M. E. P., Miraval T., Oliveira-Ramos F., Lazar C., Nikishina I., Sarychev A., Chasnyk V., Grebenkina L., Suwairi W. M. S., Koskova E., Ally M., Louw I., Breedt J., Brunner H., Ting T., Taylor J., Huggins J., Dewitt E. M., Grom A., Lovell D., Schulert G., Rodriguez-Smith J., Morris P., Sukumarain S., Gitelman M. K., Miller M., Curran M., Alperin R., Ardalan K., De Ranieri D., Hiskey M., Nolan B., Chalom B., Zelf A., Spalding S., Costanzo D., Rennebohm R., Waugaman B., Brodus E., Robinson A., Panupattanapong S., Rosenkranz M., Cassidy E., Torok K., Kingsbury D., Cartwright V., Lasky A., Brown D., Reiff A., Shaham B., Marzan K., Wagner-Weiner L., Onel K., Tesher M., Edens C., Moore T., Syed R., Pepmueller P., Tuttle P., Dalrymple A., Barhula S., Feller L., Horwitz M., Justice M., Nocton J., Olson J., Williams C., Versbsy J., Co D., Roth-Wojcicki E., Correll C., Vehe R., Binstadt B., Hobday P., Brueck D., Griffin T., Gillispie-Taylor M., Vora S., O'Neil K., Ballinger S., Blakley M., Klausmeier T., Oliver M., Stevens B., Rodriguez M., Go E., Bohnsack J., Inman C., Hersh A., Stern S., Woodward A., Durkee D., Boulva S. F., James K., Treemarcki E., Goldsmith D., Lvovich S., Toib D., Patel J., Jerath R., Sharma N., Newhall L., Carrasco R., Moorthy N., Boneparth A., Quintero A., Graham T., Spence S., Davis A., Gotte A., Mehta J., Walters H., Mian Z., Parkinson E., Hui-Yen J., Steigerwald K., Guzman M., Gottlieb B., Whitaker C., Kelly L., Succimarri R., Hazel E., Chedeville G., Compillo S., Leblance C., Tucker L., Cabral D., Houghton K., Guzman J., Morishita K., Huber A., Stringer E., Ramsey S., Lang B., Levy D., Silverman E., Schmeling H., Johnson N., Luca N., Dhalla M., Lovell, D, Tzaribachev, N, Henrickson, M, Simonini, G, Griffin, T, Alexeeva, E, Bohnsack, J, Zeft, A, Horneff, G, Vehe, R, Stanevica, V, Tarvin, S, Trachana, M, Del Rio, A, Huber, A, Kietz, D, Orban, I, Dare, J, Foeldvari, I, Quartier, P, Dominique, A, Simon, T, Martini, A, Brunner, H, Ruperto, N, Brunner, J, Fernandes, T, Appenzeller, S, Oliveira, S, Terreri, M, Minden, K, Hufnagel, M, Helling-Bakki, A, Herlin, T, Moreno, E, Anton, J, Del-Castillo, P, Udaondo, C, Penades, I, Brochard, K, Ramanan, A, Hashkes, P, Olivieri, A, Zulian, F, Montin, D, Peroni, D, Stanevicha, V, Cornejo, G, Wulffraat, N, Kamphuis, S, Gastanaga, M, Miraval, T, Oliveira-Ramos, F, Lazar, C, Nikishina, I, Sarychev, A, Chasnyk, V, Grebenkina, L, Suwairi, W, Koskova, E, Ally, M, Louw, I, Breedt, J, Ting, T, Taylor, J, Huggins, J, Dewitt, E, Grom, A, Schulert, G, Rodriguez-Smith, J, Morris, P, Sukumarain, S, Gitelman, M, Miller, M, Curran, M, Alperin, R, Ardalan, K, De Ranieri, D, Hiskey, M, Nolan, B, Chalom, B, Zelf, A, Spalding, S, Costanzo, D, Rennebohm, R, Waugaman, B, Brodus, E, Robinson, A, Panupattanapong, S, Rosenkranz, M, Cassidy, E, Torok, K, Kingsbury, D, Cartwright, V, Lasky, A, Brown, D, Reiff, A, Shaham, B, Marzan, K, Wagner-Weiner, L, Onel, K, Tesher, M, Edens, C, Moore, T, Syed, R, Pepmueller, P, Tuttle, P, Dalrymple, A, Barhula, S, Feller, L, Horwitz, M, Justice, M, Nocton, J, Olson, J, Williams, C, Versbsy, J, Co, D, Roth-Wojcicki, E, Correll, C, Binstadt, B, Hobday, P, Brueck, D, Gillispie-Taylor, M, Vora, S, O'Neil, K, Ballinger, S, Blakley, M, Klausmeier, T, Oliver, M, Stevens, B, Rodriguez, M, Go, E, Inman, C, Hersh, A, Stern, S, Woodward, A, Durkee, D, Boulva, S, James, K, Treemarcki, E, Goldsmith, D, Lvovich, S, Toib, D, Patel, J, Jerath, R, Sharma, N, Newhall, L, Carrasco, R, Moorthy, N, Boneparth, A, Quintero, A, Graham, T, Spence, S, Davis, A, Gotte, A, Mehta, J, Walters, H, Mian, Z, Parkinson, E, Hui-Yen, J, Steigerwald, K, Guzman, M, Gottlieb, B, Whitaker, C, Kelly, L, Succimarri, R, Hazel, E, Chedeville, G, Compillo, S, Leblance, C, Tucker, L, Cabral, D, Houghton, K, Guzman, J, Morishita, K, Stringer, E, Ramsey, S, Lang, B, Levy, D, Silverman, E, Schmeling, H, Johnson, N, Luca, N, Dhalla, M, Lovell D. J., Tzaribachev N., Henrickson M., Simonini G., Griffin T. A., Alexeeva E., Bohnsack J. F., Zeft A., Horneff G., Vehe R. K., Stanevica V., Tarvin S., Trachana M., Del Rio A. Q., Huber A. M., Kietz D., Orban I., Dare J., Foeldvari I., Quartier P., Dominique A., Simon T. A., Martini A., Brunner H. I., Ruperto N., Brunner J., Fernandes T., Appenzeller S., Oliveira S., Terreri M. T., Minden K., Hufnagel M., Helling-Bakki A., Herlin T., Moreno E., Anton J., Del-Castillo P. M. -., Udaondo C., Penades I. C., Brochard K., Ramanan A., Hashkes P. P., Olivieri A. N., Zulian F., Montin D., Peroni D., Stanevicha V., Cornejo G. V., Wulffraat N., Kamphuis S., Gastanaga M. E. P., Miraval T., Oliveira-Ramos F., Lazar C., Nikishina I., Sarychev A., Chasnyk V., Grebenkina L., Suwairi W. M. S., Koskova E., Ally M., Louw I., Breedt J., Brunner H., Ting T., Taylor J., Huggins J., Dewitt E. M., Grom A., Lovell D., Schulert G., Rodriguez-Smith J., Morris P., Sukumarain S., Gitelman M. K., Miller M., Curran M., Alperin R., Ardalan K., De Ranieri D., Hiskey M., Nolan B., Chalom B., Zelf A., Spalding S., Costanzo D., Rennebohm R., Waugaman B., Brodus E., Robinson A., Panupattanapong S., Rosenkranz M., Cassidy E., Torok K., Kingsbury D., Cartwright V., Lasky A., Brown D., Reiff A., Shaham B., Marzan K., Wagner-Weiner L., Onel K., Tesher M., Edens C., Moore T., Syed R., Pepmueller P., Tuttle P., Dalrymple A., Barhula S., Feller L., Horwitz M., Justice M., Nocton J., Olson J., Williams C., Versbsy J., Co D., Roth-Wojcicki E., Correll C., Vehe R., Binstadt B., Hobday P., Brueck D., Griffin T., Gillispie-Taylor M., Vora S., O'Neil K., Ballinger S., Blakley M., Klausmeier T., Oliver M., Stevens B., Rodriguez M., Go E., Bohnsack J., Inman C., Hersh A., Stern S., Woodward A., Durkee D., Boulva S. F., James K., Treemarcki E., Goldsmith D., Lvovich S., Toib D., Patel J., Jerath R., Sharma N., Newhall L., Carrasco R., Moorthy N., Boneparth A., Quintero A., Graham T., Spence S., Davis A., Gotte A., Mehta J., Walters H., Mian Z., Parkinson E., Hui-Yen J., Steigerwald K., Guzman M., Gottlieb B., Whitaker C., Kelly L., Succimarri R., Hazel E., Chedeville G., Compillo S., Leblance C., Tucker L., Cabral D., Houghton K., Guzman J., Morishita K., Huber A., Stringer E., Ramsey S., Lang B., Levy D., Silverman E., Schmeling H., Johnson N., Luca N., and Dhalla M.

Abstract

Objective: The aim of this study was to report the interim 5-year safety and effectiveness of abatacept in patients with JIA in the PRINTO/PRCSG registry. Methods: The Abatacept JIA Registry (NCT01357668) is an ongoing observational study of children with JIA receiving abatacept; enrolment started in January 2013. Clinical sites enrolled patients with JIA starting or currently receiving abatacept. Eligible patients were assessed for safety (primary end point) and effectiveness over 10 years. Effectiveness was measured by clinical 10-joint Juvenile Arthritis Disease Activity Score (cJADAS10) in patients with JIA over 5 years. As-observed analysis is presented according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Results: As of 31 March 2020, 587 patients were enrolled; 569 are included in this analysis (including 134 new users) with 1214.6 patient-years of safety data available. Over 5 years, the incidence rate (IR) per 100 patient-years of follow-up of serious adverse events was 5.52 (95% CI: 4.27, 7.01) and of events of special interest was 3.62 (95% CI: 2.63, 4.86), with 18 serious infections [IR 1.48 (95% CI: 0.88, 2.34)]. As early as month 3, 55.9% of patients achieved cJADAS10 low disease activity and inactive disease (20.3%, 72/354 and 35.6%, 126/354, respectively), sustained over 5 years. Disease activity measures improvement over 5 years across JIA categories. Conclusion: Abatacept was well tolerated in patients with JIA, with no new safety signals identified and with well-controlled disease activity, including some patients achieving inactive disease or remission.

Published
2024

5. AB1697 INCREASED INCIDENCE OF ADVERSE EVENTS AND EVENTS OF SPECIAL INTEREST WITH TREATMENT INTENSIFICATION IN NON-SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS

Author

Miettunen, P., primary, Rebollo Gimenez, A., additional, Carlini, L., additional, Pistorio, A., additional, Panaviene, V., additional, Anton, J., additional, Kamphuis, S., additional, Herlin, T., additional, Dolezalova, P., additional, Cattalini, M., additional, Susic, G., additional, Sanner, H., additional, Maggio, M. C., additional, Hashad, S., additional, Abdwani, R., additional, Rigante, D., additional, Rodriquez Lorzano, A., additional, Pallotti, C., additional, Swart, J. F., additional, and Ruperto, N., additional

Published
2024
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6. Defining remission in childhood-onset lupus: PReS-endorsed consensus definitions by an international task force

Author

Smith, E.M.D., primary, Aggarwal, A., additional, Ainsworth, J., additional, Al-Abadi, E., additional, Avcin, T., additional, Bortey, L., additional, Burnham, J., additional, Ciurtin, C., additional, Hedrich, C.M., additional, Kamphuis, S., additional, Lambert, L., additional, Levy, D.M., additional, Lewandowski, L., additional, Maxwell, N., additional, Morand, E., additional, Özen, S., additional, Pain, C.E., additional, Ravelli, A., additional, Saad Magalhaes, C., additional, Pilkington, C., additional, Schonenberg-Meinema, D., additional, Scott, C., additional, Tullus, K., additional, Beresford, M.W., additional, Goilav, B., additional, Goss, N., additional, Oni, L., additional, and Marks, S.D., additional

Published
2024
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7. Defining remission in childhood-onset lupus:PReS-endorsed consensus definitions by an international task force

Author

Smith, E. M.D., Aggarwal, A., Ainsworth, J., Al-Abadi, E., Avcin, T., Bortey, L., Burnham, J., Ciurtin, C., Hedrich, C. M., Kamphuis, S., Lambert, L., Levy, D. M., Lewandowski, L., Maxwell, N., Morand, E., Özen, S., Pain, C. E., Ravelli, A., Saad Magalhaes, C., Pilkington, C., Schonenberg-Meinema, D., Scott, C., Tullus, K., Beresford, M. W., Goilav, B., Goss, N., Oni, L., Marks, S. D., Smith, E. M.D., Aggarwal, A., Ainsworth, J., Al-Abadi, E., Avcin, T., Bortey, L., Burnham, J., Ciurtin, C., Hedrich, C. M., Kamphuis, S., Lambert, L., Levy, D. M., Lewandowski, L., Maxwell, N., Morand, E., Özen, S., Pain, C. E., Ravelli, A., Saad Magalhaes, C., Pilkington, C., Schonenberg-Meinema, D., Scott, C., Tullus, K., Beresford, M. W., Goilav, B., Goss, N., Oni, L., and Marks, S. D.

Abstract

Objective: To derive childhood-onset SLE (cSLE) specific remission definitions for future treat-to-target (T2T) trials, observational studies, and clinical practice. Methods: The cSLE International T2T Task Force conducted Delphi surveys exploring paediatric perspectives on adult-onset SLE remission targets. A modified nominal group technique was used to discuss, refine, and agree on the cSLE remission target criteria.Results: The Task Force proposed two definitions of remission: ‘cSLE clinical remission on steroids (cCR)’ and ‘cSLE clinical remission off steroids (cCR-0)’. The common criteria are: (1) Clinical-SLEDAI-2 K = 0; (2) PGA score < 0.5 (0–3 scale); (4) stable antimalarials, immunosuppressive, and biologic therapy (changes due to side-effects, adherence, weight, or when building up to target dose allowed). Criterion (3) in cCR is the prednisolone dose ≤0.1 mg/kg/day (maximum 5 mg/day), whereas in cCR-0 it is zero. Conclusions: cSLE definitions of remission have been proposed, maintaining sufficient alignment with the adult-SLE definition to facilitate life-course research.

Published
2024

9. Anakinra in Patients With Systemic Juvenile Idiopathic Arthritis: Long-term Safety From the Pharmachild Registry

Author

Giancane, G, Papa, R, Vastert, S, Bagnasco, F, Swart, J, Quartier, P, Antón, J, Kamphuis, S, Sanner, H, Glerup, M, De Benedetti, F, Tsitsami, E, Remesal, A, Moreno, E, De Inocencio, J, Myrup, C, Pallotti, C, Koné-Paut, I, Franck-Larsson, K, Malmström, H, Cederholm, S, Pistorio, A, Wulffraat, N, Ruperto, N, Giancane G, Papa R, Vastert S, Bagnasco F, Swart JF, Quartier P, Antón J, Kamphuis S, Sanner H, Glerup M, De Benedetti F, Tsitsami E, Remesal A, Moreno E, De Inocencio J, Myrup C, Pallotti C, Koné-Paut I, Franck-Larsson K, Malmström H, Cederholm S, Pistorio A, Wulffraat N, Ruperto N, Giancane, G, Papa, R, Vastert, S, Bagnasco, F, Swart, J, Quartier, P, Antón, J, Kamphuis, S, Sanner, H, Glerup, M, De Benedetti, F, Tsitsami, E, Remesal, A, Moreno, E, De Inocencio, J, Myrup, C, Pallotti, C, Koné-Paut, I, Franck-Larsson, K, Malmström, H, Cederholm, S, Pistorio, A, Wulffraat, N, Ruperto, N, Giancane G, Papa R, Vastert S, Bagnasco F, Swart JF, Quartier P, Antón J, Kamphuis S, Sanner H, Glerup M, De Benedetti F, Tsitsami E, Remesal A, Moreno E, De Inocencio J, Myrup C, Pallotti C, Koné-Paut I, Franck-Larsson K, Malmström H, Cederholm S, Pistorio A, Wulffraat N, and Ruperto N

Abstract

Objective. To evaluate the long-term safety profile of anakinra in patients with systemic juvenile idiopathic arthritis (sJIA). Methods. Data from patients with sJIA enrolled in the Pharmachild registry (ClinicalTrials.gov: NCT03932344) prior to September 30, 2018, and treated with anakinra were analyzed. The study endpoints were the occurrence of non-serious adverse events (SAEs) of at least moderate severity and SAEs, including macrophage activation syndrome (MAS), and the duration of anakinra treatment with reasons for discontinuation. All endpoints were analyzed overall by 6-month time windows, and in different treatment sets represented by those patients treated continuously with anakinra for at least 12, 18, and 24 months (set-12, -18, and -24, respectively). Results. Three hundred six patients were enrolled. Of these patients, 46%, 34%, and 28% had been treated for at least 12, 18, and 24 months, respectively. Two hundred and one AEs, mostly represented by infections, were reported for 509.3 patient-years (PY) with an overall incidence rate (IR) of 39.5 per 100 PY. Among 56 SAEs (IR 11.0/100 PY), 23.2% were infections and 19.6% MAS episodes. The IR of AEs was higher during the first 6 months of anakinra treatment, followed by decreasing IRs in the long-term treatment sets. Treatment discontinuation occurred in 76% of patients, most frequently in the first 6 months, because of inefficacy (43%), remission (31%), or AEs/intolerance (15%). No deaths or malignancies occurred during anakinra treatment. Conclusion. The results of the present study confirm the long-term safety profile of anakinra in patients with sJIA and demonstrate an overall decreasing incidence of AEs over time.

Published
2022

11. Clinical Symptoms, Laboratory Parameters and Long-Term Follow-up in a National DADA2 Cohort.

Author

Andriessen, M.V.E., Legger, G.E., Bredius, R.G.M., Gijn, M.E. van, Hak, A.E., Muller, P.C.E.H., Kamphuis, S., Klouwer, F.C.C., Kuijpers, T.W., Leavis, H.L., Nierkens, S., Rutgers, A., Veken, L.T. van der, Well, G.T.J. van, Mulders-Manders, C.M., Montfrans, J.M. van, Andriessen, M.V.E., Legger, G.E., Bredius, R.G.M., Gijn, M.E. van, Hak, A.E., Muller, P.C.E.H., Kamphuis, S., Klouwer, F.C.C., Kuijpers, T.W., Leavis, H.L., Nierkens, S., Rutgers, A., Veken, L.T. van der, Well, G.T.J. van, Mulders-Manders, C.M., and Montfrans, J.M. van

Abstract

Contains fulltext : 296537.pdf (Publisher’s version ) (Open Access), Deficiency of adenosine deaminase-2 (DADA2) is an autosomal recessive autoinflammatory disease with an extremely variable disease presentation. This paper provides a comprehensive overview of the Dutch DADA2 cohort. We performed a retrospective cohort study in 29 ADA2-deficient patients from 23 families with a median age at inclusion of 26 years. All patients had biallelic pathogenic variants in the ADA2 gene. The most common clinical findings included cutaneous involvement (79.3%), (hepato)splenomegaly (70.8%) and recurrent infections (58.6%). Stroke was observed in 41.4% of the patients. The main laboratory abnormalities were hypogammaglobulinemia and various cytopenias. Patients presented most often with a mixed phenotype involving vasculopathy, immunodeficiency and hematologic manifestations (62.1%). In this cohort, malignancies were reported in eight patients (27.6%), of whom five presented with a hematologic malignancy and two with a basal cell carcinoma. Four patients developed hemophagocytic lymphohistiocytosis (HLH) or an HLH-like episode, of whom three passed away during or shortly after the occurrence of HLH. TNF-inhibitors (TNFi) were effective in treating vasculopathy-associated symptoms and preventing stroke, but were hardly effective in the treatment of hematologic manifestations. Three patients underwent hematopoietic cell transplantation and two of them are doing well with complete resolution of DADA2-related symptoms. The overall mortality in this cohort was 17.2%. In conclusion, this cohort describes the clinical, genetic and laboratory findings of 29 Dutch DADA2 patients. We describe the occurrence of HLH as a life-threatening disease complication and report a relatively high incidence of malignancies and mortality.

Published
2023

12. Dysregulated endothelial cell markers in systemic lupus erythematosus:a systematic review and meta-analysis

Author

Bergkamp, S. C., Wahadat, M. J., Salah, A., Kuijpers, T. W., Smith, V., Tas, S. W., van den Berg, J. M., Kamphuis, S., Schonenberg-Meinema, D., Bergkamp, S. C., Wahadat, M. J., Salah, A., Kuijpers, T. W., Smith, V., Tas, S. W., van den Berg, J. M., Kamphuis, S., and Schonenberg-Meinema, D.

Abstract

Objectives: To perform a systematic literature review and meta-analysis on endothelial cell (EC) markers that are involved and dysregulated in systemic lupus erythematosus (SLE) in relation to disease activity, as EC dysregulation plays a major role in the development of premature atherosclerosis in SLE. Methods: Search terms were entered into Embase, MEDLINE, Web of Science, Google Scholar and Cochrane. Inclusion criteria were 1) studies published after 2000 reporting measurements of EC markers in serum and/or plasma of SLE patients (diagnosed according to ACR/SLICC criteria), 2) English language peer reviewed articles, and 3) disease activity measurement. For meta-analysis calculations, the Meta-Essentials tool by Erasmus Research Institute and of Management (ERIM) was used. Only those EC markers, which were 1) reported in at least two articles and 2) reported a correlation coefficient (i.e. Spearman’s rank or Pearson’s) between the measured levels of the EC marker and disease activity were included. For meta-analyses, a fixed effect model was used. Results: From 2133 hits, 123 eligible articles were selected. The identified SLE-related endothelial markers were involved in EC activation, EC apoptosis, disturbed angiogenesis, defective vascular tone control, immune dysregulation and coagulopathy. Meta-analyses of primarily cross-sectional studies showed significant associations between marker levels and disease activity for the following endothelial markers: Pentraxin-3, Thrombomodulin, VEGF, VCAM-1, ICAM-1, IP-10 and MCP-1. Dysregulated EC markers without associations with disease activity were: Angiopoeitin-2, vWF, P-Selectin, TWEAK and E-Selectin. Conclusions: We provide a complete literature overview for dysregulated EC markers in SLE comprising a wide range of different EC functions. SLE-induced EC marker dysregulation was seen with, but also without, association with disease activity. This study provides some clarity in the eminent complex field of EC mark

Published
2023

13. POS0134 LEARNING FROM LONGITUDINAL DATA IN CHILDHOOD ONSET SYSTEMIC LUPUS ERYTHEMATOSUS: WHICH BIOMARKERS HAVE PREDICTIVE VALUE FOR ENDOTHELIAL INVOLVEMENT?

Author

Bergkamp, S., primary, Bergkamp, N., additional, Wahadat, M. J., additional, Gruppen, M., additional, Nassar-Sheikh Rashid, A., additional, Kuijpers, T., additional, Tas, S., additional, Smit, M., additional, Kamphuis, S., additional, Van den Berg, J. M., additional, and Schonenberg-Meinema, D., additional

Published
2023
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14. PReS-endorsed international childhood lupus T2T task force definition of childhood lupus low disease activity state (cLLDAS)

Author

Smith, E.M.D., primary, Aggarwal, A., additional, Ainsworth, J., additional, Al-Abadi, E., additional, Avcin, T., additional, Bortey, L., additional, Burnham, J., additional, Ciurtin, C., additional, Hedrich, C.M., additional, Kamphuis, S., additional, Lambert, L., additional, Levy, D.M., additional, Lewandowski, L., additional, Maxwell, N., additional, Morand, E., additional, Ozen, S., additional, Pain, C.E., additional, Ravelli, A., additional, Saad Magalhaes, C., additional, Pilkington, C., additional, Schonenberg-Meinema, D., additional, Scott, C., additional, Tullus, K., additional, Beresford, M.W., additional, Goilav, B., additional, Oni, L., additional, and Marks, S., additional

Published
2023
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15. Additional file 2 of Dysregulated endothelial cell markers in systemic lupus erythematosus: a systematic review and meta-analysis

Author

Bergkamp, S. C., Wahadat, M. J., Salah, A., Kuijpers, T. W., Smith, V., Tas, S. W., van den Berg, J. M., Kamphuis, S., and Schonenberg-Meinema, D.

Abstract

Additional file 2. Supplementary File 2 provides an overview of all included studies in chronological order and their characteristicscorrelation with disease activity, method of blood sample analysis. Figure A. Overview of the number of articles per EC marker reporting whether or not a significant correlation between plasma/serum levels of each EC marker and validated SLE disease activity index.

Published
2023
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18. Anakinra in Patients With Systemic Juvenile Idiopathic Arthritis: Long-term Safety From the Pharmachild Registry

Author

Giancane, G. Papa, R. Vastert, S. Bagnasco, F. Swart, J.F. Quartier, P. Antón, J. Kamphuis, S. Sanner, H. Glerup, M. De Benedetti, F. Tsitsami, E. Remesal, A. Moreno, E. De Inocencio, J. Myrup, C. Pallotti, C. Koné-Paut, I. Franck-Larsson, K. Malmström, H. Cederholm, S. Pistorio, A. Wulffraat, N. Ruperto, N. the Paediatric Rheumatology International Trials Organisation (PRINTO) and Giancane, G. Papa, R. Vastert, S. Bagnasco, F. Swart, J.F. Quartier, P. Antón, J. Kamphuis, S. Sanner, H. Glerup, M. De Benedetti, F. Tsitsami, E. Remesal, A. Moreno, E. De Inocencio, J. Myrup, C. Pallotti, C. Koné-Paut, I. Franck-Larsson, K. Malmström, H. Cederholm, S. Pistorio, A. Wulffraat, N. Ruperto, N. the Paediatric Rheumatology International Trials Organisation (PRINTO)

Abstract

Objective. To evaluate the long-term safety profile of anakinra in patients with systemic juvenile idiopathic arthritis (sJIA). Methods. Data from patients with sJIA enrolled in the Pharmachild registry (ClinicalTrials.gov: NCT03932344) prior to September 30, 2018, and treated with anakinra were analyzed. The study endpoints were the occurrence of non-serious adverse events (SAEs) of at least moderate severity and SAEs, including macrophage activation syndrome (MAS), and the duration of anakinra treatment with reasons for discontinuation. All endpoints were analyzed overall by 6-month time windows, and in different treatment sets represented by those patients treated continuously with anakinra for at least 12, 18, and 24 months (set-12, -18, and -24, respectively). Results. Three hundred six patients were enrolled. Of these patients, 46%, 34%, and 28% had been treated for at least 12, 18, and 24 months, respectively. Two hundred and one AEs, mostly represented by infections, were reported for 509.3 patient-years (PY) with an overall incidence rate (IR) of 39.5 per 100 PY. Among 56 SAEs (IR 11.0/100 PY), 23.2% were infections and 19.6% MAS episodes. The IR of AEs was higher during the first 6 months of anakinra treatment, followed by decreasing IRs in the long-term treatment sets. Treatment discontinuation occurred in 76% of patients, most frequently in the first 6 months, because of inefficacy (43%), remission (31%), or AEs/intolerance (15%). No deaths or malignancies occurred during anakinra treatment. Conclusion. The results of the present study confirm the long-term safety profile of anakinra in patients with sJIA and demonstrate an overall decreasing incidence of AEs over time. © 2022 The Journal of Rheumatology.

Published
2022

19. International Consensus for the Dosing of Corticosteroids in Childhood-Onset Systemic Lupus Erythematosus With Proliferative Lupus Nephritis

Author

Chalhoub, N.E. Wenderfer, S.E. Levy, D.M. Rouster-Stevens, K. Aggarwal, A. Savani, S.I. Ruth, N.M. Arkachaisri, T. Qiu, T. Merritt, A. Onel, K. Goilav, B. Khubchandani, R.P. Deng, J. Fonseca, A.R. Ardoin, S.P. Ciurtin, C. Kasapcopur, O. Jelusic, M. Huber, A.M. Ozen, S. Klein-Gitelman, M.S. Appenzeller, S. Cavalcanti, A. Fotis, L. Lim, S.C. Silva, R.M. Miramontes, J.R. Rosenwasser, N.L. Saad-Magalhaes, C. Schonenberg-Meinema, D. Scott, C. Silva, C.A. Enciso, S. Terreri, M.T. Torres-Jimenez, A.-R. Trachana, M. Al-Mayouf, S.M. Devarajan, P. Huang, B. Brunner, H.I. Abulaban, K. Aguiar, C. Ahn, S.-Y. Akoghlanian, S. Al-Abrawi, S. Aljaberi, N. Alperin, R. Angeles-Han, S. Ardalan, K. Bader-Meunier, B. Balboni, I. Barbar-Smiley, F. Baxter, S. Beary, J. Boneparth, A. Brakeman, P. Bridges, J. Burgos-Vargas, R. Cabral, D.A. Cameto, J. Carter, C. Chang, J. Chédeville, G. Chhakchhuak, C. Chiraseveenuprapund, P. Cifuentes Alvarado, M. Concannon, A. Cooper, J. Cron, R. De Carvalho, L.M. De Quattro, K. De Ranieri, D. Dizon, B. Donnelly Wrigley, C. Duong, M.D. Eberhard, A. Ede, K. Edelheit, B. Edens, C. Espada, G. Farhey, Y. Flores, F. Fritz, D. Ganguli, S. Gilbert, M. Gittar, P. Greenbaum, L. Grom, A. Gulati, G. Harry, O. Hayward, K. Henrickson, M. Hersh, A. Hiraki, L. Hiskey, M. Hoffmann, S. Hollander, M. Hom, C. Houk, L. Houk, J.B. Hsieh, E.W.Y. Hsu, J. Jensen, P. Joos, R. Jurado, R. Jusan Fiorot, F. Kallash, M. Kamphuis, S. Keltsev, V., (deceased) Khanna, S. Kim, S. Kimseng, K.J. Knight, A. Kunder, R. Lai, J. Laskin, B. Lewandowski, L. Lim, L. Linda, W.-W. Lo, M. Lovell, D. Luggen, M. Madison, J. Mansuri, A. Martin, L. Mason, S. Miller, M. Mina, R. Mohammed, A. Moncrieffe, H. Moorthy, L. Morgan, E. Mosquera, A. Muntel, E. Muscal, E. Myones, B. Nocton, J. Ogbu, E. Okamura, D. Olson, J. Orrock, J. Paim-Marques, L. Pain, C. Park, C. Patel, P. Pereira, M. Prado, R.D. Radhakrishna, S. Rheault, M. Ridgway, W. Riskalla, M. Ronis, T. Sadun, R. Sagcal-Gironella, A.C. Santos, M.C. Schikle and Chalhoub, N.E. Wenderfer, S.E. Levy, D.M. Rouster-Stevens, K. Aggarwal, A. Savani, S.I. Ruth, N.M. Arkachaisri, T. Qiu, T. Merritt, A. Onel, K. Goilav, B. Khubchandani, R.P. Deng, J. Fonseca, A.R. Ardoin, S.P. Ciurtin, C. Kasapcopur, O. Jelusic, M. Huber, A.M. Ozen, S. Klein-Gitelman, M.S. Appenzeller, S. Cavalcanti, A. Fotis, L. Lim, S.C. Silva, R.M. Miramontes, J.R. Rosenwasser, N.L. Saad-Magalhaes, C. Schonenberg-Meinema, D. Scott, C. Silva, C.A. Enciso, S. Terreri, M.T. Torres-Jimenez, A.-R. Trachana, M. Al-Mayouf, S.M. Devarajan, P. Huang, B. Brunner, H.I. Abulaban, K. Aguiar, C. Ahn, S.-Y. Akoghlanian, S. Al-Abrawi, S. Aljaberi, N. Alperin, R. Angeles-Han, S. Ardalan, K. Bader-Meunier, B. Balboni, I. Barbar-Smiley, F. Baxter, S. Beary, J. Boneparth, A. Brakeman, P. Bridges, J. Burgos-Vargas, R. Cabral, D.A. Cameto, J. Carter, C. Chang, J. Chédeville, G. Chhakchhuak, C. Chiraseveenuprapund, P. Cifuentes Alvarado, M. Concannon, A. Cooper, J. Cron, R. De Carvalho, L.M. De Quattro, K. De Ranieri, D. Dizon, B. Donnelly Wrigley, C. Duong, M.D. Eberhard, A. Ede, K. Edelheit, B. Edens, C. Espada, G. Farhey, Y. Flores, F. Fritz, D. Ganguli, S. Gilbert, M. Gittar, P. Greenbaum, L. Grom, A. Gulati, G. Harry, O. Hayward, K. Henrickson, M. Hersh, A. Hiraki, L. Hiskey, M. Hoffmann, S. Hollander, M. Hom, C. Houk, L. Houk, J.B. Hsieh, E.W.Y. Hsu, J. Jensen, P. Joos, R. Jurado, R. Jusan Fiorot, F. Kallash, M. Kamphuis, S. Keltsev, V., (deceased) Khanna, S. Kim, S. Kimseng, K.J. Knight, A. Kunder, R. Lai, J. Laskin, B. Lewandowski, L. Lim, L. Linda, W.-W. Lo, M. Lovell, D. Luggen, M. Madison, J. Mansuri, A. Martin, L. Mason, S. Miller, M. Mina, R. Mohammed, A. Moncrieffe, H. Moorthy, L. Morgan, E. Mosquera, A. Muntel, E. Muscal, E. Myones, B. Nocton, J. Ogbu, E. Okamura, D. Olson, J. Orrock, J. Paim-Marques, L. Pain, C. Park, C. Patel, P. Pereira, M. Prado, R.D. Radhakrishna, S. Rheault, M. Ridgway, W. Riskalla, M. Ronis, T. Sadun, R. Sagcal-Gironella, A.C. Santos, M.C. Schikle

Abstract

Objective: To develop a standardized steroid dosing regimen (SSR) for physicians treating childhood-onset systemic lupus erythematosus (SLE) complicated by lupus nephritis (LN), using consensus formation methodology. Methods: Parameters influencing corticosteroid (CS) dosing were identified (step 1). Data from children with proliferative LN were used to generate patient profiles (step 2). Physicians rated changes in renal and extrarenal childhood-onset SLE activity between 2 consecutive visits and proposed CS dosing (step 3). The SSR was developed using patient profile ratings (step 4), with refinements achieved in a physician focus group (step 5). A second type of patient profile describing the course of childhood-onset SLE for ≥4 months since kidney biopsy was rated to validate the SSR-recommended oral and intravenous (IV) CS dosages (step 6). Patient profile adjudication was based on majority ratings for both renal and extrarenal disease courses, and consensus level was set at 80%. Results: Degree of proteinuria, estimated glomerular filtration rate, changes in renal and extrarenal disease activity, and time since kidney biopsy influenced CS dosing (steps 1 and 2). Considering these parameters in 5,056 patient profile ratings from 103 raters, and renal and extrarenal course definitions, CS dosing rules of the SSR were developed (steps 3–5). Validation of the SSR for up to 6 months post–kidney biopsy was achieved with 1,838 patient profile ratings from 60 raters who achieved consensus for oral and IV CS dosage in accordance with the SSR (step 6). Conclusion: The SSR represents an international consensus on CS dosing for use in patients with childhood-onset SLE and proliferative LN. The SSR is anticipated to be used for clinical care and to standardize CS dosage during clinical trials. © 2021, American College of Rheumatology

Published
2022

20. Gene signature fingerprints stratify SLE patients in groups with similar biological disease profiles: a multicentre longitudinal study

Author

Wahadat, M.J., Schonenberg-Meinema, D., Helden-Meeuwsen, C.G. van, Tilburg, S.J. van, Groot, Noortje, Schatorje, E.J.H., Hoppenreijs, E.P., Muller, P.C., Brinkman, D.M., Dvorak, D., Verkaaik, M., Berg, J.Merlijn van den, Bouchalova, K., Kamphuis, S., Versnel, M.A., Wahadat, M.J., Schonenberg-Meinema, D., Helden-Meeuwsen, C.G. van, Tilburg, S.J. van, Groot, Noortje, Schatorje, E.J.H., Hoppenreijs, E.P., Muller, P.C., Brinkman, D.M., Dvorak, D., Verkaaik, M., Berg, J.Merlijn van den, Bouchalova, K., Kamphuis, S., and Versnel, M.A.

Abstract

Item does not contain fulltext, OBJECTIVES: Clinical phenotyping and predicting treatment responses in SLE patients is challenging. Extensive blood transcriptional profiling has identified various gene modules that are promising for stratification of SLE patients. We aimed to translate existing transcriptomic data into simpler gene signatures suitable for daily clinical practice. METHODS: Real-time PCR of multiple genes from the IFN M1.2, IFN M5.12, neutrophil (NPh) and plasma cell (PLC) modules, followed by a principle component analysis, was used to identify indicator genes per gene signature. Gene signatures were measured in longitudinal samples from two childhood-onset SLE cohorts (n = 101 and n = 34, respectively), and associations with clinical features were assessed. Disease activity was measured using Safety of Estrogen in Lupus National Assessment (SELENA)-SLEDAI. Cluster analysis subdivided patients into three mutually exclusive fingerprint-groups termed (1) all-signatures-low, (2) only IFN high (M1.2 and/or M5.12) and (3) high NPh and/or PLC. RESULTS: All gene signatures were significantly associated with disease activity in cross-sectionally collected samples. The PLC-signature showed the highest association with disease activity. Interestingly, in longitudinally collected samples, the PLC-signature was associated with disease activity and showed a decrease over time. When patients were divided into fingerprints, the highest disease activity was observed in the high NPh and/or PLC group. The lowest disease activity was observed in the all-signatures-low group. The same distribution was reproduced in samples from an independent SLE cohort. CONCLUSIONS: The identified gene signatures were associated with disease activity and were indicated to be suitable tools for stratifying SLE patients into groups with similar activated immune pathways that may guide future treatment choices.

Published
2022

21. International Consensus for the Dosing of Corticosteroids in Childhood-Onset Systemic Lupus Erythematosus With Proliferative Lupus Nephritis

Author

Chalhoub, N.E. Wenderfer, S.E. Levy, D.M. Rouster-Stevens, K. Aggarwal, A. Savani, S.I. Ruth, N.M. Arkachaisri, T. Qiu, T. Merritt, A. Onel, K. Goilav, B. Khubchandani, R.P. Deng, J. Fonseca, A.R. Ardoin, S.P. Ciurtin, C. Kasapcopur, O. Jelusic, M. Huber, A.M. Ozen, S. Klein-Gitelman, M.S. Appenzeller, S. Cavalcanti, A. Fotis, L. Lim, S.C. Silva, R.M. Miramontes, J.R. Rosenwasser, N.L. Saad-Magalhaes, C. Schonenberg-Meinema, D. Scott, C. Silva, C.A. Enciso, S. Terreri, M.T. Torres-Jimenez, A.-R. Trachana, M. Al-Mayouf, S.M. Devarajan, P. Huang, B. Brunner, H.I. Abulaban, K. Aguiar, C. Ahn, S.-Y. Akoghlanian, S. Al-Abrawi, S. Aljaberi, N. Alperin, R. Angeles-Han, S. Ardalan, K. Bader-Meunier, B. Balboni, I. Barbar-Smiley, F. Baxter, S. Beary, J. Boneparth, A. Brakeman, P. Bridges, J. Burgos-Vargas, R. Cabral, D.A. Cameto, J. Carter, C. Chang, J. Chédeville, G. Chhakchhuak, C. Chiraseveenuprapund, P. Cifuentes Alvarado, M. Concannon, A. Cooper, J. Cron, R. De Carvalho, L.M. De Quattro, K. De Ranieri, D. Dizon, B. Donnelly Wrigley, C. Duong, M.D. Eberhard, A. Ede, K. Edelheit, B. Edens, C. Espada, G. Farhey, Y. Flores, F. Fritz, D. Ganguli, S. Gilbert, M. Gittar, P. Greenbaum, L. Grom, A. Gulati, G. Harry, O. Hayward, K. Henrickson, M. Hersh, A. Hiraki, L. Hiskey, M. Hoffmann, S. Hollander, M. Hom, C. Houk, L. Houk, J.B. Hsieh, E.W.Y. Hsu, J. Jensen, P. Joos, R. Jurado, R. Jusan Fiorot, F. Kallash, M. Kamphuis, S. Keltsev, V., (deceased) Khanna, S. Kim, S. Kimseng, K.J. Knight, A. Kunder, R. Lai, J. Laskin, B. Lewandowski, L. Lim, L. Linda, W.-W. Lo, M. Lovell, D. Luggen, M. Madison, J. Mansuri, A. Martin, L. Mason, S. Miller, M. Mina, R. Mohammed, A. Moncrieffe, H. Moorthy, L. Morgan, E. Mosquera, A. Muntel, E. Muscal, E. Myones, B. Nocton, J. Ogbu, E. Okamura, D. Olson, J. Orrock, J. Paim-Marques, L. Pain, C. Park, C. Patel, P. Pereira, M. Prado, R.D. Radhakrishna, S. Rheault, M. Ridgway, W. Riskalla, M. Ronis, T. Sadun, R. Sagcal-Gironella, A.C. Santos, M.C. Schikler, K. AL Suwairi, W. Siddiqi, N. Silva, M.F. Singh-Grewal, D. Smitherman, E. Smolewska, E. Son, M.B. Srinivasalu, H. Sule, S. Susic, G. Syed, R. Thatayatikom, A. Ting, T. Toth, M. Turnier, J. Vashisht, P. Vega Fernandez, P. Velasquez, M. von Scheven, E. Wahezi, D. Ware, A. Wu, E. Yan, J. Yildirim-Toruner, C. Zamparo, C. Zhang, Y. Lawson, E. for the Childhood Arthritis Rheumatology Research Alliance Lupus Nephritis Work Group the Pediatric Rheumatology European Society Lupus Working Party

Abstract

Objective: To develop a standardized steroid dosing regimen (SSR) for physicians treating childhood-onset systemic lupus erythematosus (SLE) complicated by lupus nephritis (LN), using consensus formation methodology. Methods: Parameters influencing corticosteroid (CS) dosing were identified (step 1). Data from children with proliferative LN were used to generate patient profiles (step 2). Physicians rated changes in renal and extrarenal childhood-onset SLE activity between 2 consecutive visits and proposed CS dosing (step 3). The SSR was developed using patient profile ratings (step 4), with refinements achieved in a physician focus group (step 5). A second type of patient profile describing the course of childhood-onset SLE for ≥4 months since kidney biopsy was rated to validate the SSR-recommended oral and intravenous (IV) CS dosages (step 6). Patient profile adjudication was based on majority ratings for both renal and extrarenal disease courses, and consensus level was set at 80%. Results: Degree of proteinuria, estimated glomerular filtration rate, changes in renal and extrarenal disease activity, and time since kidney biopsy influenced CS dosing (steps 1 and 2). Considering these parameters in 5,056 patient profile ratings from 103 raters, and renal and extrarenal course definitions, CS dosing rules of the SSR were developed (steps 3–5). Validation of the SSR for up to 6 months post–kidney biopsy was achieved with 1,838 patient profile ratings from 60 raters who achieved consensus for oral and IV CS dosage in accordance with the SSR (step 6). Conclusion: The SSR represents an international consensus on CS dosing for use in patients with childhood-onset SLE and proliferative LN. The SSR is anticipated to be used for clinical care and to standardize CS dosage during clinical trials. © 2021, American College of Rheumatology

Published
2022

22. Anakinra in Patients With Systemic Juvenile Idiopathic Arthritis: Long-term Safety From the Pharmachild Registry

Author

Giancane G, Papa R, Vastert S, Bagnasco F, Swart JF, Quartier P, Anton-Lopez J, Kamphuis S, Sanner H, Glerup M, De Benedetti F, Tsitsami E, Remesal A, Moreno E, De Inocencio J, Myrup C, Pallotti C, Koné-Paut I, Franck-Larsson K, Malmström H, Cederholm S, Pistorio A, Wulffraat N, Ruperto N, and Paediatric Rheumatology International Trials Organisation (PRINTO)

Subjects
systemic juvenile idiopathic arthritis, long-term adverse effects, anakinra
Abstract

OBJECTIVE: To evaluate the long-term safety profile of anakinra in patients with systemic juvenile idiopathic arthritis (sJIA). METHODS: Data from patients with sJIA enrolled in the Pharmachild registry (ClinicalTrials.gov: NCT03932344) prior to September 30, 2018, and treated with anakinra were analyzed. The study endpoints were the occurrence of non-serious adverse events (SAEs) of at least moderate severity and SAEs, including macrophage activation syndrome (MAS), and the duration of anakinra treatment with reasons for discontinuation. All endpoints were analyzed overall by 6-month time windows, and in different treatment sets represented by those patients treated continuously with anakinra for at least 12, 18, and 24 months (set-12, -18, and -24, respectively). RESULTS: Three hundred six patients were enrolled. Of these patients, 46%, 34%, and 28% had been treated for at least 12, 18, and 24 months, respectively. Two hundred and one AEs, mostly represented by infections, were reported for 509.3 patient-years (PY) with an overall incidence rate (IR) of 39.5 per 100 PY. Among 56 SAEs (IR 11.0/100 PY), 23.2% were infections and 19.6% MAS episodes. The IR of AEs was higher during the first 6 months of anakinra treatment, followed by decreasing IRs in the long-term treatment sets. Treatment discontinuation occurred in 76% of patients, most frequently in the first 6 months, because of inefficacy (43%), remission (31%), or AEs/intolerance (15%). No deaths or malignancies occurred during anakinra treatment. CONCLUSION: The results of the present study confirm the long-term safety profile of anakinra in patients with sJIA and demonstrate an overall decreasing incidence of AEs over time. [ClinicalTrials.gov: NCT01399281 and NCT03932344].

Published
2022

24. Opportunistic infections in immunosuppressed patients with juvenile idiopathic arthritis: analysis by the Pharmachild Safety Adjudication Committee

Author

Giancane G1, Swart JF2, Castagnola E3, Groll AH4, Horneff G5, 6, Huppertz HI7, Lovell DJ8, Wolfs T2, Herlin T9, Dolezalova P10, Sanner H11, Susic G13, Sztajnbok F14, Maritsi D15, Constantin T16, Vargova V17, Sawhney S18, Rygg M19, K Oliveira S21, Cattalini M22, Bovis F1, Bagnasco F1, Pistorio A23, Martini A24, Wulffraat N2, Ruperto N25, Paediatric Rheumatology International Trials Organisation (PRINTO). Cuttica R, Garay SM, Brunner J, Emminger W, Appenzeller S, Len C, Saad Magalhaes C, Telcharova-Mihaylovska A, Harjacek M, Jelusic M, Estmann A, Nielsen S, Herrera Mora C, Gervais E, Koné-Paut I, Quartier P, Foeldvari I, Horneff G, Lutz T, Minden K, Tzaribachev N, Trachana M, Tsitsami E, Vougiouka O, Orban I, Harel L, Hashkes P, Uziel Y, Cimaz R, Civino A, Consolini R, D'Angelo G, De Benedetti F, Filocamo G, Fueri E, Gallizzi R, Maggio MC, Magnolia MG, Miniaci A, Montin D, Olivieri A. N., Pastore S, Rigante D, Zulian F, Rumba-Rozenfelde I, Stanevicha V, Panaviene V, Rodriguez Lozano AL, Rubio-Perez N, Vega Cornejo G, Hoppenreijs E, Kamphuis S, Flato B, Nordal EB, Abdwani R, Miraval T, Paz Gastanaga ME, Smolewska E, Ailioaie C, Cochino AV, Laday M, Lazar C, Alexeeva E, Chasnyk V, Keltsev V, Suwairi WMS, Vijatov-Djuric G, Vojinovic J, Arkachaisri T, Koskova E, Avcin T, Ally M, Van Rensburg CJ, Louw I, Lopez JA, Boteanu AL, Calvo Penades I, De Inocencio J, Mesa-Del-Castillo P, Moreno E, Remesal A, Hofer M, Gok F, Ozen S, Ramanan A, Pallotti C, Villa L., Giancane, G1, Swart, Jf2, Castagnola, E3, Groll, Ah4, Horneff, G5, Huppertz, Hi7, Lovell, Dj8, Wolfs, T2, Herlin, T9, Dolezalova, P10, Sanner, H11, Susic, G13, Sztajnbok, F14, Maritsi, D15, Constantin, T16, Vargova, V17, Sawhney, S18, Rygg, M19, K Oliveira, S21, Cattalini, M22, Bovis, F1, Bagnasco, F1, Pistorio, A23, Martini, A24, Wulffraat, N2, Ruperto, N25, Paediatric Rheumatology International Trials Organisation (PRINTO)., Cuttica R, Garay, Sm, Brunner, J, Emminger, W, Appenzeller, S, Len, C, Saad Magalhaes, C, Telcharova-Mihaylovska, A, Harjacek, M, Jelusic, M, Estmann, A, Nielsen, S, Herrera Mora, C, Gervais, E, Koné-Paut, I, Quartier, P, Foeldvari, I, Horneff, G, Lutz, T, Minden, K, Tzaribachev, N, Trachana, M, Tsitsami, E, Vougiouka, O, Orban, I, Harel, L, Hashkes, P, Uziel, Y, Cimaz, R, Civino, A, Consolini, R, D'Angelo, G, De Benedetti, F, Filocamo, G, Fueri, E, Gallizzi, R, Maggio, Mc, Magnolia, Mg, Miniaci, A, Montin, D, Olivieri, A. N., Pastore, S, Rigante, D, Zulian, F, Rumba-Rozenfelde, I, Stanevicha, V, Panaviene, V, Rodriguez Lozano, Al, Rubio-Perez, N, Vega Cornejo, G, Hoppenreijs, E, Kamphuis, S, Flato, B, Nordal, Eb, Abdwani, R, Miraval, T, Paz Gastanaga, Me, Smolewska, E, Ailioaie, C, Cochino, Av, Laday, M, Lazar, C, Alexeeva, E, Chasnyk, V, Keltsev, V, Suwairi, Wm, Vijatov-Djuric, G, Vojinovic, J, Arkachaisri, T, Koskova, E, Avcin, T, Ally, M, Van Rensburg, Cj, Louw, I, Lopez, Ja, Boteanu, Al, Calvo Penades, I, De Inocencio, J, Mesa-Del-Castillo, P, Moreno, E, Remesal, A, Hofer, M, Gok, F, Ozen, S, Ramanan, A, Pallotti, C, Villa, L., Giancane, Gabriella, Swart, Joost F, Castagnola, Elio, Groll, Andreas H, Horneff, Gerd, Huppertz, Hans-Iko, Lovell, Daniel J, Wolfs, Tom, Herlin, Troel, Dolezalova, Pavla, Sanner, Helga, Susic, Gordana, Sztajnbok, Flavio, Maritsi, Despoina, Constantin, Tama, Vargova, Veronika, Sawhney, Sujata, Rygg, Marite, K Oliveira, Sheila, Cattalini, Marco, Bovis, Francesca, Bagnasco, Francesca, Pistorio, Angela, Martini, Alberto, Wulffraat, Nico, Ruperto, Nicolino, Cuttica, Ruben, Garay, Stella Mari, Brunner, Jurgen, Emminger, Wolfgang, Appenzeller, Simone, Len, Claudio, Saad Magalhaes, Claudia, Telcharova-Mihaylovska, Albena, Harjacek, Miroslav, Jelusic, Marija, Estmann, Anne, Nielsen, Susan, Herrera Mora, Cristina, Gervais, Elisabeth, Koné-Paut, Isabelle, Quartier, Pierre, Foeldvari, Ivan, Lutz, Thoma, Minden, Kirsten, Tzaribachev, Nikolay, Trachana, Maria, Tsitsami, Elena, Vougiouka, Olga, Orban, Ilonka, Harel, Liora, Hashkes, Philip, Uziel, Yosef, Cimaz, Rolando, Civino, Adele, Consolini, Rita, D'Angelo, Gianfranco, De Benedetti, Fabrizio, Filocamo, Giovanni, Fueri, Elena, Gallizzi, Romina, Maggio, Maria Cristina, Magnolia, Maria Greca, Miniaci, Angela, Montin, Davide, Olivieri, Alma Nunzia, Pastore, Serena, Rigante, Donato, Zulian, Francesco, Rumba-Rozenfelde, Ingrida, Stanevicha, Valda, Panaviene, Violeta, Rodriguez Lozano, Ana Luisa, Rubio-Perez, Nadina, Vega Cornejo, Gabriel, Hoppenreijs, Esther, Kamphuis, Sylvia, Flato, Berit, Nordal, Ellen Berit, Abdwani, Reem, Miraval, Tatiana, Paz Gastanaga, Maria Eliana, Smolewska, Elzbieta, Ailioaie, Constantin, Cochino, Alexis-Virgil, Laday, Matilda, Lazar, Calin, Alexeeva, Ekaterina, Chasnyk, Vyacheslav, Keltsev, Vladimir, Suwairi, Wafaa Mohammed Saad, Vijatov-Djuric, Gordana, Vojinovic, Jelena, Arkachaisri, Thaschawee, Koskova, Elena, Avcin, Tadej, Ally, Mahmood, Van Rensburg, Christa Janse, Louw, Ingrid, Lopez, Jordi Anton, Boteanu, Alina Lucica, Calvo Penades, Inmaculada, De Inocencio, Jaime, Mesa-Del-Castillo, Pablo, Moreno, Estefania, Remesal, Agustin, Hofer, Michael, Gok, Faysal, Ozen, Seza, Ramanan, Athimalaipet, Pallotti, Chiara, Villa, Luca, and Pediatrics

Subjects
Male, lcsh:Diseases of the musculoskeletal system, Biologic, Paediatrics: 760 [VDP], Artritis infecciosa, MedDRA, Infants malalts, Arthritis, Severity of Illness Index, Hospital patients, Cohort Studies, Pharmacovigilance, 0302 clinical medicine, 030212 general & internal medicine, Registries, Child, Biologics, Immunosuppressive therapy, Infections, Juvenile idiopathic arthritis, Opportunistic, biologics, immunosuppressive therapy, infections, juvenile idiopathic arthritis, opportunistic, Barneleddgikt, 3. Good health, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Antirheumatic Agents, Child, Preschool, Cohort, Pediatric Infectious Disease, Female, Infection, Research Article, medicine.medical_specialty, Tuberculosis, juvenil idiopathic arthritis, Opportunistic Infections, Herpes Zoster, 03 medical and health sciences, Immunocompromised Host, Juvenile idiopathic arthriti, Internal medicine, medicine, Humans, book, 030203 arthritis & rheumatology, Malalts hospitalitzats, Immunosupressió, business.industry, Sick children, medicine.disease, Rheumatology, Arthritis, Juvenile, Infectious arthritis, Pediatri: 760 [VDP], Orthopedic surgery, Opportunistiske infeksjoner, book.journal, lcsh:RC925-935, business, Infeccions oportunistes, Immunosuppression
Abstract

Background: To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee (SAC). Methods: The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI. Results: A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) were adjudicated as infections, of them 603/682 (88.4%) as common and 119/682 (17.4%) as OI by the SAC. Matching these 119 opportunistic events with the provisional list, 106 were confirmed by the SAC as OI, and among them infections by herpes viruses were the most frequent (68%), followed by tuberculosis (27.4%). The remaining events were divided in the groups of non-OI and possible/patient and/or pathogen-related OI. Conclusions: We found a significant number of OI in JIA patients on immunosuppressive therapy. The proposed list of OI, created by consensus and validated in the Pharmachild cohort, could facilitate comparison among future pharmacovigilance studies. © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Published
2020
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30. OP0164 LONG-TERM SAFETY OF ANAKINRA IN PATIENTS WITH SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS FROM THE PHARMACHILD REGISTRY

Author

Giancane, G., primary, Papa, R., additional, Vastert, S., additional, Bagnasco, F., additional, Swart, J. F., additional, Quartier, P., additional, Hofer, M., additional, Anton, J., additional, Kamphuis, S., additional, Sanner, H., additional, Glerup, M., additional, De Benedetti, F., additional, Tsitsami, E., additional, Remesal, A., additional, Moreno Ruzafa, E., additional, De Inocencio, J., additional, Myrup, C., additional, Pallotti, C., additional, Koné-Paut, I., additional, Franck-Larsson, K., additional, Malmstrom, H., additional, Cederholm, S., additional, Pistorio, A., additional, Wulffraat, N., additional, and Ruperto, N., additional

Published
2021
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32. POS0178 GENE SIGNATURE FINGERPRINTS DIVIDE SLE PATIENTS IN SUBGROUPS WITH COMPARABLE BIOLOGICAL DISEASE PROFILES: A MULTICENTRE LONGITUDINAL STUDY

Author

Wahadat, M. J., primary, Van Helden-Meeuwsen, C. G., additional, Van Tilburg, S., additional, Schatorjé, E., additional, Hoppenreijs, E., additional, Hissink Muller, P. C. E., additional, Van den Berg, J. M., additional, Schonenberg-Meinema, D., additional, Kamphuis, S., additional, and Versnel, M., additional

Published
2021
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34. Anticarbamylated protein (anti-CarP) antibodies are present in sera of juvenile idiopathic arthritis (JIA) patients

Author

Muller, P C E Hissink, Anink, J, Shi, J, Levarht, E W N, Reinards, T H C M, Otten, M H, van Tol, M J D, Jol-van der Zijde, C M, Brinkman, D M C, Allaart, C F, Hoppenreijs, E P, Koopman-Keemink, Y, Kamphuis, S S M, Dolman, K, van den Berg, J M, van Rossum, M A J, van Suijlekom-Smit, L W A, Schilham, M W, Huizinga, T W J, Toes, R E M, ten Cate, R, and Trouw, L A

Published
2013
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37. Identification of an Amino Acid Motif in HLA–DRβ1 That Distinguishes Uveitis in Patients With Juvenile Idiopathic Arthritis

Author

Haasnoot, A.M.J.W., Schilham, M.W., Kamphuis, S., Muller, P.C.E.H., Heiligenhaus, A., Foell, D., Minden, K., Ophoff, R.A., Radstake, T.R.D.J., Hollander, A.I. den, Reinards, T.H.C.M., Hiddingh, S., Schalij-Delfos, N.E., Hoppenreijs, E.P.A.H., Rossum, M.A.J. van, Wouters, C., Saurenmann, R.K., Berg, J.M. van den, Wulffraat, N.M., Cate, R. ten, Boer, J.H. de, Pulit, S.L., Kuiper, J.J.W., ICON-JIA Study Grp, Pediatrics, General Paediatrics, AII - Amsterdam institute for Infection and Immunity, AII - Inflammatory diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, and University of Zurich

Subjects
0301 basic medicine, Male, Linkage disequilibrium, genetic structures, 2745 Rheumatology, Amino Acid Motifs, Medizin, Arthritis, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], Cohort Studies, Genotype, Odds Ratio, Immunology and Allergy, Child, biology, Child, Preschool, 2723 Immunology and Allergy, Female, Uveitis, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], musculoskeletal diseases, Adolescent, Immunology, 610 Medicine & health, Human leukocyte antigen, Major histocompatibility complex, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Rheumatology, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, Alleles, Genetic Association Studies, 2403 Immunology, business.industry, Odds ratio, medicine.disease, Arthritis, Juvenile, eye diseases, 030104 developmental biology, 10036 Medical Clinic, Genetic Loci, biology.protein, business, HLA-DRB1 Chains
Abstract

Objective: Uveitis is a visually debilitating disorder that affects up to 30% of children with the most common forms of juvenile idiopathic arthritis (JIA). The disease mechanisms predisposing only a subgroup of children to uveitis are unknown. This study was undertaken to identify genetic susceptibility loci for uveitis in JIA, using a genome-wide association study in 522 children with JIA. Methods: Two cohorts of JIA patients with ophthalmologic follow-up data were genotyped. Data were then imputed using a genome-wide imputation reference panel, and an HLA-specific reference panel was used for imputing amino acids and HLA types in the major histocompatibility complex (MHC). After imputation, genome-wide and MHC-specific analyses were performed, and a reverse immunology approach was utilized to model antigen presentation at 13 common HLA–DRβ1 alleles. Results: Presence of the amino acid serine at position 11 (serine 11) in HLA–DRβ1 was associated with an increased risk of uveitis in JIA patients (odds ratio [OR] 2.60, P = 5.43 × 10−10) and was specific to girls (Pfemales = 7.61 × 10−10 versus Pmales = 0.18). Serine 11 resides in the YST motif in the peptide-binding groove of HLA–DRβ1; all 3 amino acids in this motif are in perfect linkage disequilibrium and show identical association with disease. Quantitative prediction of binding affinity revealed that HLA–DRβ1 alleles with the YST motif could be distinguished on the basis of discernable peptide-binding preferences. Conclusion: These findings highlight a genetically distinct, sexually dimorphic feature of JIA with uveitis as compared to JIA without uveitis. The association could be indicative of the potential involvement of antigen presentation by HLA–DRβ1 in the development of uveitis in JIA. The results of this study may advance our progress toward improved treatments for, and possible prevention of, the sight-threatening complications of uveitis in children with JIA.

Published
2018
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41. Erratum: European consensus-based recommendations for the diagnosis and treatment of rare paediatric vasculitides - The SHARE initiative (Rheumatology (2019)58 (656-671) DOI: 10.1093/rheumatology/key322)

Author

De Graeff, N., Groot, N., Brogan, P., Ozen, S., Avcin, T., Bader-Meunier, B., Dolezalova, P., Feldman, B. M., Kone-Paut, I., Lahdenne, P., Marks, S. D., Mccann, L., Pilkington, C., Ravelli, A., Van Royen, A., Uziel, Y., Vastert, B., Wulffraat, N., Kamphuis, S., and Beresford, M. W.

Published
2020

44. Opportunistic infections in immunosuppressed patients with juvenile idiopathic arthritis: Analysis by the Pharmachild Safety Adjudication Committee

Author

Giancane, G. Swart, J.F. Castagnola, E. Groll, A.H. Horneff, G. Huppertz, H.-I. Lovell, D.J. Wolfs, T. Herlin, T. Dolezalova, P. Sanner, H. Susic, G. Sztajnbok, F. Maritsi, D. Constantin, T. Vargova, V. Sawhney, S. Rygg, M. Oliveira, S.K. Cattalini, M. Bovis, F. Bagnasco, F. Pistorio, A. Martini, A. Wulffraat, N. Ruperto, N. Cuttica, R. Garay, S.M. Brunner, J. Emminger, W. Appenzeller, S. Len, C. Saad Magalhaes, C. Telcharova-Mihaylovska, A. Harjacek, M. Jelusic, M. Estmann, A. Nielsen, S. Herrera Mora, C. Gervais, E. Koné-Paut, I. Quartier, P. Foeldvari, I. Horneff, G. Lutz, T. Minden, K. Tzaribachev, N. Trachana, M. Tsitsami, E. Vougiouka, O. Orban, I. Harel, L. Hashkes, P. Uziel, Y. Cimaz, R. Civino, A. Consolini, R. D'Angelo, G. De Benedetti, F. Filocamo, G. Fueri, E. Gallizzi, R. Maggio, M.C. Magnolia, M.G. Miniaci, A. Montin, D. Olivieri, A.N. Pastore, S. Rigante, D. Zulian, F. Rumba-Rozenfelde, I. Stanevicha, V. Panaviene, V. Rodriguez Lozano, A.L. Rubio-Perez, N. Vega Cornejo, G. Hoppenreijs, E. Kamphuis, S. Flato, B. Nordal, E.B. Abdwani, R. Miraval, T. Paz Gastanaga, M.E. Smolewska, E. Ailioaie, C. Cochino, A.-V. Laday, M. Lazar, C. Alexeeva, E. Chasnyk, V. Keltsev, V. Suwairi, W.M.S. Vijatov-Djuric, G. Vojinovic, J. Arkachaisri, T. Koskova, E. Avcin, T. Ally, M. Van Rensburg, C.J. Louw, I. Lopez, J.A. Boteanu, A.L. Calvo Penades, I. De Inocencio, J. Mesa-Del-Castillo, P. Moreno, E. Remesal, A. Hofer, M. Gok, F. Ozen, S. Ramanan, A. Pallotti, C. Villa, L. and Giancane, G. Swart, J.F. Castagnola, E. Groll, A.H. Horneff, G. Huppertz, H.-I. Lovell, D.J. Wolfs, T. Herlin, T. Dolezalova, P. Sanner, H. Susic, G. Sztajnbok, F. Maritsi, D. Constantin, T. Vargova, V. Sawhney, S. Rygg, M. Oliveira, S.K. Cattalini, M. Bovis, F. Bagnasco, F. Pistorio, A. Martini, A. Wulffraat, N. Ruperto, N. Cuttica, R. Garay, S.M. Brunner, J. Emminger, W. Appenzeller, S. Len, C. Saad Magalhaes, C. Telcharova-Mihaylovska, A. Harjacek, M. Jelusic, M. Estmann, A. Nielsen, S. Herrera Mora, C. Gervais, E. Koné-Paut, I. Quartier, P. Foeldvari, I. Horneff, G. Lutz, T. Minden, K. Tzaribachev, N. Trachana, M. Tsitsami, E. Vougiouka, O. Orban, I. Harel, L. Hashkes, P. Uziel, Y. Cimaz, R. Civino, A. Consolini, R. D'Angelo, G. De Benedetti, F. Filocamo, G. Fueri, E. Gallizzi, R. Maggio, M.C. Magnolia, M.G. Miniaci, A. Montin, D. Olivieri, A.N. Pastore, S. Rigante, D. Zulian, F. Rumba-Rozenfelde, I. Stanevicha, V. Panaviene, V. Rodriguez Lozano, A.L. Rubio-Perez, N. Vega Cornejo, G. Hoppenreijs, E. Kamphuis, S. Flato, B. Nordal, E.B. Abdwani, R. Miraval, T. Paz Gastanaga, M.E. Smolewska, E. Ailioaie, C. Cochino, A.-V. Laday, M. Lazar, C. Alexeeva, E. Chasnyk, V. Keltsev, V. Suwairi, W.M.S. Vijatov-Djuric, G. Vojinovic, J. Arkachaisri, T. Koskova, E. Avcin, T. Ally, M. Van Rensburg, C.J. Louw, I. Lopez, J.A. Boteanu, A.L. Calvo Penades, I. De Inocencio, J. Mesa-Del-Castillo, P. Moreno, E. Remesal, A. Hofer, M. Gok, F. Ozen, S. Ramanan, A. Pallotti, C. Villa, L.

Abstract

Background: To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee (SAC). Methods: The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI. Results: A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) were adjudicated as infections, of them 603/682 (88.4%) as common and 119/682 (17.4%) as OI by the SAC. Matching these 119 opportunistic events with the provisional list, 106 were confirmed by the SAC as OI, and among them infections by herpes viruses were the most frequent (68%), followed by tuberculosis (27.4%). The remaining events were divided in the groups of non-OI and possible/patient and/or pathogen-related OI. Conclusions: We found a significant number of OI in JIA patients on immunosuppressive therapy. The proposed list of OI, created by consensus and validated in the Pharmachild cohort, could facilitate comparison among future pharmacovigilance studies. Trial registration: Clinicaltrials.gov NCT 01399281; ENCePP seal: awarded on 25 November 2011. © 2020 The Author(s).

Published
2020

47. Opportunistic infections in immunosuppressed patients with juvenile idiopathic arthritis: analysis by the Pharmachild Safety Adjudication Committee

Author

Giancane, G, Swart, Jf, Castagnola, E, Groll, Ah, Horneff, G, Huppertz, Hi, Lovell, Dj, Wolfs, T, Herlin, T, Dolezalova, P, Sanner, H, Susic, G, Sztajnbok, F, Maritsi, D, Constantin, T, Vargova, V, Sawhney, S, Rygg, M, K Oliveira, S, Cattalini, M, Bovis, F, Bagnasco, F, Pistorio, A, Martini, A, Wulffraat, N, Ruperto, N, Cuttica, R, Garay, Sm, Brunner, J, Emminger, W, Appenzeller, S, Len, C, Saad Magalhaes, C, Telcharova-Mihaylovska, A, Harjacek, M, Jelusic, M, Estmann, A, Nielsen, S, Herrera Mora, C, Gervais, E, Koné-Paut, I, Quartier, P, Foeldvari, I, Lutz, T, Minden, K, Tzaribachev, N, Trachana, M, Tsitsami, E, Vougiouka, O, Orban, I, Harel, L, Hashkes, P, Uziel, Y, Cimaz, R, Civino, A, Consolini, R, D'Angelo, G, De Benedetti, F, Filocamo, G, Fueri, E, Gallizzi, R, Maggio, Mc, Magnolia, Mg, Miniaci, A, Montin, D, Olivieri, An, Pastore, S, Rigante, Donato, Zulian, F, Rumba-Rozenfelde, I, Stanevicha, V, Panaviene, V, Rodriguez Lozano, Al, Rubio-Perez, N, Vega Cornejo, G, Hoppenreijs, E, Kamphuis, S, Flato, B, Nordal, Eb, Abdwani, R, Miraval, T, Paz Gastanaga, Me, Smolewska, E, Ailioaie, C, Cochino, Av, Laday, M, Lazar, C, Alexeeva, E, Chasnyk, V, Keltsev, V, Suwairi, Wm, Vijatov-Djuric, G, Vojinovic, J, Arkachaisri, T, Koskova, E, Avcin, T, Ally, M, Van Rensburg, Cj, Louw, I, Lopez, Ja, Boteanu, Al, Calvo Penades, I, De Inocencio, J, Mesa-Del-Castillo, P, Moreno, E, Remesal, A, Hofer, M, Gok, F, Ozen, S, Ramanan, A, Pallotti, C, Villa, L &amp, Paediatric Rheumatology International Trials Organisation, (PRINTO), Rigante D (ORCID:0000-0001-7032-7779), Giancane, G, Swart, Jf, Castagnola, E, Groll, Ah, Horneff, G, Huppertz, Hi, Lovell, Dj, Wolfs, T, Herlin, T, Dolezalova, P, Sanner, H, Susic, G, Sztajnbok, F, Maritsi, D, Constantin, T, Vargova, V, Sawhney, S, Rygg, M, K Oliveira, S, Cattalini, M, Bovis, F, Bagnasco, F, Pistorio, A, Martini, A, Wulffraat, N, Ruperto, N, Cuttica, R, Garay, Sm, Brunner, J, Emminger, W, Appenzeller, S, Len, C, Saad Magalhaes, C, Telcharova-Mihaylovska, A, Harjacek, M, Jelusic, M, Estmann, A, Nielsen, S, Herrera Mora, C, Gervais, E, Koné-Paut, I, Quartier, P, Foeldvari, I, Lutz, T, Minden, K, Tzaribachev, N, Trachana, M, Tsitsami, E, Vougiouka, O, Orban, I, Harel, L, Hashkes, P, Uziel, Y, Cimaz, R, Civino, A, Consolini, R, D'Angelo, G, De Benedetti, F, Filocamo, G, Fueri, E, Gallizzi, R, Maggio, Mc, Magnolia, Mg, Miniaci, A, Montin, D, Olivieri, An, Pastore, S, Rigante, Donato, Zulian, F, Rumba-Rozenfelde, I, Stanevicha, V, Panaviene, V, Rodriguez Lozano, Al, Rubio-Perez, N, Vega Cornejo, G, Hoppenreijs, E, Kamphuis, S, Flato, B, Nordal, Eb, Abdwani, R, Miraval, T, Paz Gastanaga, Me, Smolewska, E, Ailioaie, C, Cochino, Av, Laday, M, Lazar, C, Alexeeva, E, Chasnyk, V, Keltsev, V, Suwairi, Wm, Vijatov-Djuric, G, Vojinovic, J, Arkachaisri, T, Koskova, E, Avcin, T, Ally, M, Van Rensburg, Cj, Louw, I, Lopez, Ja, Boteanu, Al, Calvo Penades, I, De Inocencio, J, Mesa-Del-Castillo, P, Moreno, E, Remesal, A, Hofer, M, Gok, F, Ozen, S, Ramanan, A, Pallotti, C, Villa, L &amp, Paediatric Rheumatology International Trials Organisation, (PRINTO), and Rigante D (ORCID:0000-0001-7032-7779)

Abstract

BACKGROUND: To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee (SAC). METHODS: The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI. RESULTS: A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) were adjudicated as infections, of them 603/682 (88.4%) as common and 119/682 (17.4%) as OI by the SAC. Matching these 119 opportunistic events with the provisional list, 106 were confirmed by the SAC as OI, and among them infections by herpes viruses were the most frequent (68%), followed by tuberculosis (27.4%). The remaining events were divided in the groups of non-OI and possible/patient and/or pathogen-related OI. CONCLUSIONS: We found a significant number of OI in JIA patients on immunosuppressive therapy. The proposed list of OI, created by consensus and validated in the Pharmachild cohort, could facilitate comparison among future pharmacovigilance studies.

Published
2020

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