Efficacy and Safety of Anti-TNFα Therapy for Uveitis Associated with Juvenile Idiopathic Arthritis: A Systematic Review and Meta-Analysis

Abstract

Introduction: To investigate the efficacy and safety of anti-TNFα therapy in patients with juvenile idiopathic arthritis associated uveitis (JIA-U).

Methods: Embase, PubMed, Cochrane Library, and Web of Science were systematically searched for studies reporting anti-TNFα treatment in patients with JIA-U. The primary outcome was the control of intraocular inflammation (CII). The pooled proportion of CII was assessed by the random-effects method when I² > 50%, otherwise, by the fixed-effect method. This study was registered with PROSPERO (CRD42020161749).

Results: Three randomized clinical trials (RCTs), twelve case series, three retrospective cohort studies, and three case reports were identified. A total of 399 patients were receiving anti-TNFα therapy, of which 201 patients were treated with adalimumab (ADA), 139 with infliximab (IFX), 36 with etanercept (ETA), 20 with golimumab (GLM), and 3 with certolizumab pegol (CZP). The pooled proportions of CII on observational studies were 82% (95% CI 63-96%) in patients receiving ADA, 56% (95% CI 30-80%) in IFX, 38% (95% CI 8-73%) in ETA and 65% (95% CI 42-86%) in GLM, respectively. All three patients treated with CZP reached improved activity. ADA therapy led to a significantly higher proportion of CII compared to IFX therapy (χ² = 26.24, P < 0.001), or to ETA therapy (χ² = 13.43, P < 0.001); but no statistical difference was observed between IFX and ETA (χ² = 0.13, P = 0.71). As to safety, most reported adverse events were tolerable and two cohort studies consistently showed that ADA was safer than IFX.

Conclusions: The existing evidence suggests that ADA is better than IFX regarding efficacy and safety. The effectiveness of IFX is higher than ETA with no statistical difference. GLM and CZP may be proxies for ADA but the evidence is limited.

Keywords: Anti-TNFα therapy; Efficacy; Juvenile idiopathic arthritis; Meta-analysis.

Fig. 1

The flow diagram of literature identification. ADA adalimumab, IFX infliximab, ETA etanercept, GLM golimumab, CZP certolizumab pegol

Fig. 2

Forest plot on the pooled proportion of intraocular inflammation control with the treatment of adalimumab (a), infliximab (b), etanercept (c), respectively. As I² statistic showed the obvious heterogeneity of the studies, random-effects model were used to present the pooled results

Fig. 3

Funnel plots on intraocular inflammation control in children with JIA-U regarding to adalimumab (ADA), infliximab (IFX), etanercept (ETA)