Title: Beyond corticosteroids: TNF-? inhibitors as the emerging standard of care in non-infectious uveitis
Abstract:
Aims: This comprehensive review aims to evaluate the mechanism, long-term safety, efficacy, and disease-specific applications of tumour necrosis factor-alpha (TNF-α) inhibitors in the treatment of non-infectious uveitis and their role in reducing corticosteroid dependence.
Methods: Systematic searches of PubMed, Embase and Cochrane Library (2005– 2025) identified randomized trials and observational cohorts of adults and children with non infectious uveitis treated with systemic adalimumab, infliximab or golimumab; two reviewers independently screened studies and extracted data, and findings were synthesized narratively with emphasis on inflammation control, visual outcomes, corticosteroid sparing and serious adverse events.
Results: Adalimumab and infliximab demonstrate compelling evidence for superior inflammation control compared to conventional corticosteroid therapy. In juvenile idiopathic arthritis-associated uveitis, adalimumab reduced treatment failure from 60% (placebo) to 27%, with uveitis relapse rates decreasing significantly from 1.6/year to 0.7/year (p<0.001). Visual acuity improvements were substantial, with 76% of eyes achieving anterior chamber inflammation resolution. In Behçet's disease associated uveitis, infliximab showed superior efficacy in sight-threatening presentations, improving Best Corrected Visual Acuity (BCVA) from 0.44 to 0.63 (p<0.0001) over two years with reduced macular oedema and intraocular inflammation. Golimumab achieved clinical remission in 87% (13/15) of refractory spondyloarthropathy-related uveitis cases previously refractory to other TNF-α inhibitors, demonstrating significant corticosteroid-sparing effects. Additionally, golimumab reduced acute anterior uveitis occurrence by 80.2% in spondylarthritis patients whilst providing sustained systemic disease control, particularly benefiting patients with recurrent uveitis. Long term prospective follow-up studies (8-10 years) demonstrated sustained remission rates of 97% with infliximab and 67-87% with adalimumab, with 75% of Behçet's patients continuing infliximab beyond 10 years. Most patients successfully reduced or discontinued corticosteroids. However, significant adverse events occurred including opportunistic infections (tuberculosis), malignancies (acute myeloid leukaemia, melanomas), and demyelinating disease, with variable incidence between agents. Infliximab showed higher immunogenicity related complications and infusion reactions, whilst adalimumab demonstrated a relatively favourable safety profile despite occasional serious adverse events.
Conclusion: TNF-α inhibitors represent a paradigm shift in non-infectious uveitis management, transforming outcomes in individuals refractory to corticosteroid therapy and systemic disease-associated cases with substantial improvements in vision and quality of life. Clear disease-specific efficacy has emerged, adalimumab for juvenile idiopathic arthritis associated uveitis, infliximab for acute sight threatening presentations such as Behçet's disease, and golimumab for refractory spondyloarthritis-associated uveitis and anterior uveitis prevention. The significant corticosteroid sparing capacity mitigates adverse effects of prolonged steroid use, including cataracts and elevated intraocular pressure. However, serious long-term safety concerns necessitate rigorous pharmacovigilance and informed patient selection. Larger randomised controlled trials are needed to establish optimal treatment plans, identify predictors of treatment response and determine the length of remission beyond current follow-up periods.
