Tocilizumab in management of refractory juvenile idiopathic arthritis, 10 years of experience at tertiary university hospital

Mohammed A. Muzaffer1, Abobakr A. Abdelgalil2,1
1Department of Pediatrics, King Abdulaziz University, Jeddah, Saudi Arabia
2Department of Pediatrics, Cairo University, Cairo, Egypt

Tóm tắt

Juvenile idiopathic arthritis (JIA) is the most prevalent pediatric rheumatic disorder. Progress in modalities of therapy improves the disease outcome. We aimed to determine the efficacy and safety of tocilizumab (TCZ) in the management of systemic (sJIA) and polyarticular (pJIA) in children who are resistant to conventional as well as other biological therapies. In this retrospective study, we selected JIA patients according to the International League of Association for Rheumatology (ILAR) criteria and were treated with TCZ. Response to TCZ was assessed using Juvenile Arthritis Disease Activity Score-10 (JADAS-10) and also outcomes were assessed according to the American College of Rheumatology (ACR) remission criteria. Safety of the drug was assessed by documenting possibly related adverse effects (AE). Statistical analysis using SPSS version 25 with statistical significance is considered if p ≤ 0.05. We included 16 JIA patients aged ≤ 18 years but 2 of them were excluded as they developed severe reaction during the TCZ 1st dose, so finally, 14 patients were included. The median age of our patients was 12 years. Of these 14 patients, 9 (64.3%) had sJIA and 5 (35.7%) had pJIA. TCZ use led to significant improvement in the JADAS-10 from mean 22.4 (± 7.9) when it was initially assessed and then 3, 6, 12, and 24 months after TCZ initiation with means 5.7 (± 3.9), 4.4 (± 3.7), 3.5 (± 3.1), and 2.7 (± 2.2), (P = 0.001, 0.001, 0.005, 0.012), respectively. Five patients exhibited TCZ possibly expected side effects. Neutropenia and infusion-related reactions were the most frequent AE. Tocilizumab seems to be generally effective and safe drug in the management of sJIA and pJIA especially in cases refractory to conventional as well as other biologic agents.

Từ khóa


Tài liệu tham khảo

Giani T, Madera A, Cimaz R (2020) Association of juvenile idiopathic arthritis and morphea: a case series. Clin Rheumatol 39:1341–1345. https://doi.org/10.1007/s10067-019-04850-5

Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, He X, Maldonado-Cocco J, Orozco-Alcala J, Prieur AM, Suarez-Almazor ME, Woo P, International League of Associations for Rheumatology (2004) International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 31:390–392

Viswanathan V, Murray KJ (2016) Management of children with juvenile idiopathic arthritis. Indian J Pediatr 83:63–70. https://doi.org/10.1007/s12098-015-1966-1

Kasapçopur Ö, Barut K (2015) Treatment in juvenile rheumatoid arthritis and new treatment options. Turk Pediatri Ars 50:1–10

Seaman SC, Hong S, Dlouhy BJ, Menezes AH (2020) Current management of juvenile idiopathic arthritis affecting the craniovertebral junction. Childs Nerv Syst 36:1529–1538

Dağdeviren-Çakır A, Arvas A, Barut K, Gür E, Kasapçopur Ö (2016) Serum vitamin D levels during activation and remission periods of patients with juvenile idiopathic arthritis and familial Mediterranean fever. Turk J Pediatr 58:125–131

Turnier JL, Brunner HI (2016) Tocilizumab for treating juvenile idiopathic arthritis. Expert Opin Biol Ther 16:559–566

Grönlund MM, Remes-Pakarinen T, Kröger L, Markula-Patjas K, Backström M, Putto-Laurila A, Aalto K, Vähäsalo P (2020) Efficacy and safety of tocilizumab in a real-life observational cohort of patients with polyarticular juvenile idiopathic arthritis. Rheumatology (Oxford) 59:732–741. https://doi.org/10.1093/rheumatology/kez291

Mehta J, Beukelman T (2017) Biologic agents in the treatment of childhood-onset rheumatic disease. J Pediatr 189:31–39. https://doi.org/10.1016/j.jpeds.2017.06.041

Opoka-Winiarska V, Żuber Z, Alexeeva E, Chasnyk V, Nikishina I, Dębowska G, Smolewska E (2018) Long-term, interventional, open-label extension study evaluating the safety of tocilizumab treatment in patients with polyarticular-course juvenile idiopathic arthritis from Poland and Russia who completed the global, international CHERISH trial. Clin Rheumatol 37:1807–1816. https://doi.org/10.1007/s10067-018-4071-9

Roszkiewicz J, Orczyk K, Smolewska E (2018) Tocilizumab in the treatment of systemic-onset juvenile idiopathic arthritis - single-centre experience. Reumatologia 56:279–284. https://doi.org/10.5114/reum.2018.79497

Ruiz-Medrano J, Díaz-Valle D, Cuiña R, Gegúndez JA, Chhablani J, Majumder PD, Gutierrez-Bonet R (2018) The role of tocilizumab in the treatment of inflammatory diseases of the eye and orbit: a useful alternative. J Fr Ophtalmol 41:759–766. https://doi.org/10.1016/j.jfo.2018.02.006

Yazılıtaş F, Özdel S, Şimşek D, Aydoğ Ö, Çakıcı EK, Can GG, Güngör T, Bülbül M (2019) Tocilizumab for juvenile idiopathic arthritis: a single-center case series. Sao Paulo Med J 137:517–522. https://doi.org/10.1590/1516-3180.2018.0489220719

Yasuoka R, Iwata N, Abe N, Kohagura T, Nakaseko H, Shimizu M, Kawabe S (2019) Risk factors for hypersensitivity reactions to tocilizumab introduction in systemic juvenile idiopathic arthritis. Mod Rheumatol 29:324–327. https://doi.org/10.1080/14397595.2018.1457490

Al-Mayouf SM, Alenazi A, AlJasser H (2016) Biologic agents therapy for Saudi children with rheumatic diseases: indications and safety. Int J Rheum Dis 19:600–605. https://doi.org/10.1111/1756-185X.12365

Consolaro A, Bracciolini G, Ruperto N, Pistorio A, Magni-Manzoni S, Malattia C, Pederzoli S, Davì S, Martini A, Ravelli A (2012) Paediatric Rheumatology International Trials Organization. Remission, minimal disease activity, and acceptable symptom state in juvenile idiopathic arthritis: defining criteria based on the juvenile arthritis disease activity score. Arthritis Rheum 64:2366–2374. https://doi.org/10.1002/art.34373

Consolaro A, Ruperto N, Bracciolini G, Frisina A, Gallo MC, Pistorio A, Verazza S, Negro G, Gerloni V, Goldenstein-Schainberg C, Sztajnbok F, Wulffraat NM, Martini A, Ravelli A, Paediatric Rheumatology International Trials Organization (PRINTO) (2014) Defining criteria for high disease activity in juvenile idiopathic arthritis based on the juvenile arthritis disease activity score. Ann Rheum Dis 73:1380–1383 TCZ ref vancouver.docx

Demirkaya E, Consolaro A, Sonmez HE, Giancane G, Simsek D, Ravelli A (2016) Current research in outcome measures for pediatric rheumatic and autoinflammatory diseases. Curr Rheumatol Rep 18:8

Klotsche J, Raab A, Niewerth M, Sengler C, Ganser G, Kallinich T, Niehues T, Hufnagel M, Thon A, Hospach T, Horneff G, Minden K (2016) Outcome and trends in treatment of systemic juvenile idiopathic arthritis in the german national pediatric rheumatologic database, 2000-2013. Arthritis Rheumatol 68:3023–3034

Wallace CA, Giannini EH, Huang B, Itert L, Ruperto N, Childhood Arthritis Rheumatology Research Alliance, Pediatric Rheumatology Collaborative Study Group, Paediatric Rheumatology International Trials Organisation (2011) American College of Rheumatology provisional criteria for defining clinical inactive disease in select categories of juvenile idiopathic arthritis. Arthritis Care Res 63:929–936

Walkovich K, Boxer LA (2013) How to approach neutropenia in childhood. Pediatr Rev 34:173–184. https://doi.org/10.1542/pir.34-4-173

Ravelli A, Minoia F, Davì S, Horne A, Bovis F, Pistorio A, Aricò M et al (2016) 2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: a European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. Arthritis Rheumatol 68:566–576. https://doi.org/10.1002/art.39332

De Benedetti F, Brunner HI, Ruperto N, Kenwright A, Wright S, Calvo I, Cuttica R et al (2012) Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med 367:2385–2395. https://doi.org/10.1056/NEJMoa1112802

Brunner HI, Ruperto N, Zuber Z, Keane C, Harari O, Kenwright A, Lu P et al (2015) Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial. Ann Rheum Dis 74:1110–1117. https://doi.org/10.1136/annrheumdis-2014-205351

Brunner HI, Ruperto N, Zuber Z, Cuttica R, Keltsev V, Xavier RM, Burgos-Vargas R et al (2020) Efficacy and safety of tocilizumab for polyarticular-course juvenile idiopathic arthritis in the open-label 2-year extension of a phase 3 trial. Arthritis Rheumatol. https://doi.org/10.1002/art.41528

Horneff G, Schulz AC, Klotsche J, Hospach A, Minden K, Foeldvari I, Trauzeddel R, Ganser G, Weller-Heinemann F, Haas JP (2017) Experience with etanercept, tocilizumab and interleukin-1 inhibitors in systemic onset juvenile idiopathic arthritis patients from the BIKER registry. Arthritis Res Ther 19:256. https://doi.org/10.1186/s13075-017-1462-2

Demir S, Sönmez HE, Arslanoğlu-Aydın E, Özen S, Bilginer Y (2019) Tocilizumab treatment in juvenile idiopathic arthritis patients: a single center experience. Turk J Pediatr 61:180–185. https://doi.org/10.24953/turkjped.2019.02.005

Klein A, Klotsche J, Hügle B, Minden K, Hospach A, Weller-Heinemann F, Schwarz T et al (2020) Long-term surveillance of biologic therapies in systemic-onset juvenile idiopathic arthritis: data from the German BIKER registry. Rheumatology 59:2287–2298. https://doi.org/10.1093/rheumatology/kez577

Pardeo M, Wang J, Ruperto N, Alexeeva E, Chasnyk V, Schneider R, Horneff G et al (2019) Neutropenia during tocilizumab treatment is not associated with infection risk in systemic or polyarticular-course juvenile idiopathic arthritis. J Rheumatol 46:1117–1126. https://doi.org/10.3899/jrheum.180795