Background To date, no biologic treatments other than tocilizumab (TCZ) have been approved in active Systemic Juvenile Idiopathic Arthritis (SJIA). Some however are used off label. Published evidence on their efficacy in SJIA is scarce, and there is no head-to-head data from randomised clinical trials (RCT) on the comparative efficacy of biologic treatments in SJIA.
Objectives This analysis considers the current evidence on ACR responses of SJIA patients on biologics (used on and off label), synthesises this information, and explores efficacy differences.
Methods A systematic literature review was conducted to identify RCTs that report ACR responses of SJIA patients on any biologic treatment, initially limited to SJIA, then extended to include any JIA subtype population. Reported ACR responses were compared with TCZ responses from the TENDER study,1 using an adjusted indirect comparison, comparing the relative risks of the clinical trials.2 The following outcomes were considered; ACR30 response with absence of fever, ACR30 response alone, ACR50, ACR70 and ACR90 response. Where needed, reported ACR responses were corrected to control for the differences in subtype disease.
Results The initial literature review identified only one RCT with data on anakinra (ANK).3 The extension of the review yielded more results. However, only one additional study, with evidence on infliximab (INF), was deemed appropriate for comparison with TENDER, due to study design.4 The indirect comparison on ACR30 response without fever shows that patients on TCZ are more likely to achieve this outcome with TCZ than with ANK, although not statistically significant (RR=1.91; CI.: 0.84, 4.37). In ACR30 response alone the analysis shows statistical significance in favour of TCZ (RR=2.37 CI.: 1.10, 5.10). ACR50, 70 and 90 responses were not reported. In the comparison with INF, assuming no correction for the differences in the population subtype between the trials, patients treated with TCZ are also significantly more likely to reach ACR 30 response (RR=2.85 CI.: 1.38, 5.87), as well as ACR50 and ACR70 response. If a correction is applied the response with TCZ increases comparing to INF. ACR90 response was not reported.
Conclusions There is a dearth of evidence in the literature to infer on efficacy differences across all biologics used for the treatment of SJIA patients. Based on the current evidence and the analysis conducted, patients on TCZ, the only approved biologic treatment for SJIA to date, are roughly 2-3 times more likely to achieve ACR response than if treated with ANK or INF.
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Bucher HC, Guyatt GH, Griffith LE et al. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 1997;50:683-91.
Quartier P, Allantaz F, Cimaz R et al. A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial). Ann Rheum Dis 2011;70:747–754.
Ruperto N, Lovell DJ, Cuttica R et al. A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum. 2007 Sep;56(9):3096-106.
Disclosure of Interest A. Diamantopoulos Consultant for: Hoffman-La Roche, C. LeReun Consultant for: Hoffman-La Roche, R. Westhovens Consultant for: Hoffman-La Roche, F. Dejonckheere Employee of: Hoffman-LaRoche