Background The biological agents (BAs) have revolutionized the care and have improved the prognosis of juvenile idiopathic arthritis (JIA). Effectiveness and short-term tolerance was well established in randomized clinical trials (RCTs), initially in JIA. However, there is an insufficient evidence for the long-term tolerance1. The serious adverse events (SAEs) include infections, malignancies and drug induced auto-immune diseases (e.g. uveitis).
Objectives To assess the benefit/risk balance of BAs assessed by RCTs vs placebo or vs standard treatment in JIA, using meta-analysis (MA) technique.
Methods All RCTs in JIA comparing BAs to placebo or standard treatment (e.g. methotrexate) published between 1950 and February 2016 were eligible. Data source: Cochrane, Medline, ClinicalTrial.gov register. The ILAR classification for JIA2 was used and the clinical efficacy of treatment was measured by the ACR pediatric score3. Efficacy was analyzed considering the design of study. Effectiveness (ACRpedi30) was estimated as the measure of the benefit of the BAs and SAEs as a measure of risk by random effect models. The benefit/risk balance was analyzed using the net efficacy adjusted for risk (NEAR)4. An OR >1 indicates that the treatment has a beneficial effect and OR <1 a deleterious effect. Subgroups analyses were made to account the heterogeneity of JIA. We explored potential heterogeneity by subgroups analysis according with BAs and JIA subtypes.
Results We included 20 RCTs conducted in JIA encompassing 1533 children. The disease duration, at the inclusion of RCTs, varies between 2 and 6 years for most studies. The maintenance of the therapeutic effect was estimated in the studies using withdrawal design in 6 studies. The maintenance of clinical response showed a large heterogeneity. Sub-groups analyses showed that the heterogeneity is marked in the systemic JIA5. The global NEAR OR was in favor of BAs in parallel (OR 3.83, CI 1.49–9.82) and withdrawal (OR 2.75, CI 1.51–5.01) trials. The efficacy of BAs in JIA was superior to the placebo in parallel (OR 5.46, CI 2.26–13.21) and withdrawal (OR 3.52, CI 2.15–5.77) trials. In RCTs (parallel and withdrawal design), SAEs did not differ between BAs and control (OR 1.18, CI 0.73–1.9). No death occurred at follow-up.
Conclusions This is the first MA assessing all BAs used in all JIA categories combined. This MA in patients with JIA shows that the benefit/risk ratio of BAs in JIA is favorable.
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Boada, J. N. et al. Net efficacy adjusted for risk (NEAR): a simple procedure for measuring risk:benefit balance. PloS One 3, e3580 (2008).
Tarp, S. et al. Efficacy and safety of biological agents for systemic juvenile idiopathic arthritis: a systematic review and meta-analysis of randomized trials. Rheumatol. Oxf. Engl. 55, 669–679 (2016).
Disclosure of Interest None declared