Incidence of anterior uveitis in patients with axial spondyloarthritis treated with anti-TNF or anti-IL17A: a systematic review, a pairwise and network meta-analysis of randomized controlled trials

Abstract

Background Anterior uveitis (AU) is the most frequent extra-articular feature of axial spondyloarthritis (axSpA). We aimed to assess and compare the incidence of AU in axSpA patients treated with anti-TNF or anti-IL17A. Methods We systematically reviewed PubMed, EMBase, and Cochrane from inception to May 3, 2020, and searched for placebo-controlled and head-to-head randomized controlled trials (RCTs) assessing anti-TNF monoclonal antibodies (mAb) or soluble receptor fusion protein or anti-IL17A in patients with axSpA according to ASAS criteria and reporting safety data on AU. Data were extracted following a predefined protocol. We did pairwise and network meta-analyses for the primary outcome of AU flares (relapse or de novo) incidence and estimated summary odds ratios (ORs). We assessed the quality of evidence using the Cochrane risk-of-bias 2.0 tool. We ranked treatments according to their effectiveness in preventing AU flare using the P-score. Results We identified 752 citations and included 33 RCTs, comprising 4544 treated patients (anti-TNF mAb 2101, etanercept [ETN] 699, anti-IL17A 1744) and 2497 placebo-receiving patients. Incidence of uveitis was lower with anti-TNF mAb versus placebo (OR = 0.46; CI 95% [0.24; 0.90]) and versus anti-IL17A (OR = 0.34; CI 95% [0.12; 0.92]. According to the P-score, the ranking from the most to the least preventive treatment of uveitis flare was as follows: anti-TNF mAb, ETN, placebo, and anti-IL17A. Conclusion In RCTs assessing anti-TNF and anti-IL17A in axSpA, incident uveitis are rare events. However, this network meta-analysis demonstrates that anti-TNF mAb are associated with a lower incidence of uveitis compared to placebo and anti-IL17A.

Upadacitinib in active ankylosing spondylitis: results of the 2-year, double-blind, placebo-controlled SELECT-AXIS 1 study and open-label extension

“…The events occurred in 10 patients, of which 9 patients had a history of uveitis. The event and incidence rates of uveitis with upadacitinib were consistent with previous studies with monoclonal tumour necrosis factor inhibitors and interleukin-17 inhibitors 36–38. In the 2-year study, one AE of colitis was reported in a young man without a history of IBD, resulting in an overall IBD event rate of 0.3/100 PY.…”

“…The event and incidence rates of uveitis with upadacitinib were consistent with previous studies with monoclonal tumour necrosis factor inhibitors and interleukin-17 inhibitors. [36][37][38] In the 2-year study, one AE of colitis was reported in a young man without a history of IBD, resulting in an overall IBD event rate of 0.3/100 PY. There were no new onsets of IBD among 4 patients who entered the study with a history of IBD at baseline.…”

Incidence of Uveitis in Patients With Axial Spondylarthritis Treated With Biologics or Targeted Synthetics: A Systematic Review and Network Meta‐Analysis

“…The results of this study contrast those of the NMA published by Roche et al, 11 which reported a decreased incidence of AU with anti‐TNF mAb compared with anti–IL‐17A (odds ratio 0.34, 95% CI 0.12–0.92). There are several likely explanations for why we did not observe similar findings.…”

Analysis of Single‐Cell Transcriptome and Surface Protein Expression in Ankylosing Spondylitis Identifies OX40‐Positive and Glucocorticoid‐Induced Tumor Necrosis Factor Receptor–Positive Pathogenic Th17 Cells

“…Although Th17 cells have been involved in the induction of inflammation, using an IL-17A blocker to treat patients with inflammatory bowel disease has resulted in disease aggravation (12). Moreover, antibody therapies targeting IL-17A have been ineffective for bowel inflammation or uveitis in AS (13,14), in contrast to the marked effectiveness for psoriasis (15,16). However, emerging data suggest that not all Th17 cells are pathogenic.…”