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

Katie Bechman, Zijing Yang, Maryam Adas, et al; ARTHRITIS RHEUMATOLOGY, 20 December 2023 May 15, 2024, 9 a.m.

Presented By

Dr Walter Maksymowych MB ChB, FRCP(C), FACP
Chief Medical Officer, CARE Arthritis; Professor of Medicine, University of Alberta

Guest Commentary By:

Dr. Jonathan Chan MD, FRCPC
Clinical Associate Professor, University of British Columbia

Synopsis

Introduction
  • RCTs and observational data demonstrate efficacy of TNFi but not IL17i monoclonal antibodies or etanercept for acute anterior uveitis (AAU) associated with axSpA1 (Nguyen et al.) (Dick et al.) (Wendling et al.) (Guignard et al.) (Lie et al.) (Lindström et al.)
  • EULAR 2022 and ACR2019 treatment recommendations recommend TNFi as preferred DMARD when axSpA patients have concomitant AAU (Ramiro et al.) (Ward et al.)
  • Network meta-analysis demonstrated lower risk of AAU with TNFi versus IL17i bioDMARD in axSpA (Roche et al.)
  • This SLR was aimed at updating the analyses to include data from upadacitinib and bimekizumab RCTs
Methods
  • SLR used MEDLINE and EMBASE and was run to December 2023
  • Included all placebo-controlled RCTs of TNFi, IL17i, and JAKi in AS and nr-axSpA plus their open label extensions
  • Primary outcome was AAU events (new onset and relapse)
  • Pooled estimates of the relative risk of AAU between each treatment arm and placebo were compared using Network Meta-Analysis (NMA) and expressed as incidence rate ratios (IRRs) with 95% CIs
Results
  • 44 placebo-controlled RCTs were included
  • 26 studies reported on AAU during the trial period in their safety analyses.
  • IRs of AAU per 100 patient-years were 4.1[95% CI 0–8.5] for TNFi mAbs, 5.4 [95% CI 0–16.0] for etanercept, 2.8 [95% CI 1.6–4.1] for IL-17i, and 1.5 [95% CI 0.0–3.0] for JAKi.
  • In the pooled placebo group, IRs were 10.8 [95% CI 7.4–14.1] per 100 person-years.
  • IL-17i was the only group to demonstrate a statistically significant lower IRR compared to placebo.

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Commentary

A valid NMA should satisfy the assumption of transitivity i.e. that there are no systematic differences between the studies other than the treatments being compared. But only 28 studies reported on history of AAU at baseline and where this was reported the proportion of patients with a history of AAU ranged from 3% to 46% between RCTs, with some imbalance between the treatment and placebo groups. A prior history of AAU is a major risk factor for de novo AAU events. In one study the incidence of AAU flares on one TNFi mAb, adalimumab, was 14 per 100 patient-years, with 43% having a prior history of AAU (van Denderen et al.). In the RHAPSODY study, the incidence of AAU flares on adalimumab was 7.4 per 100 patient-years, with 22% having a history of AAU (Rudwaleit et al.). Combining data from bimekizumab RCTs, this agent inhibiting both IL17A and -F, with data from other IL17i RCTs may not be appropriate in view of recent data suggesting benefit for AAU in axSpA (Rudwaleit et al.), while studies of IL17i in non-infectious AAU RCTs did not show benefit (Dick et al.).

Special Guest Commentary

This interesting study assessed whether TNF, IL17, and JAK inhibitors lowered the risk of AAU. There is strong evidence that TNF inhibitors are effective in treating and preventing flares of uveitis. Previous studies of IL17A inhibitors in non-infecious AAU did not show benefit. More recent data presented at ACR showed a lower incidence of AAU in patients treated with bimekizumab and secondary analysis of upadacitinib also showed reduced AAU events. A previous NMA published by Roche et al showed a reduction of AAU events with TNF but not with IL17. This study showed TNF, IL17, and JAK inhibitors all reduced rates of AAU. The different result of this study may have been due to combining IL17A and A/F data. We have not seen data on AAU events from secukinumab and ixekizumab trials in AxSpA or PsA.

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