What is the treatment for uveitis in patients with ankylosing spondylitis?

Treatment of Uveitis in Ankylosing Spondylitis

All patients with AS and acute uveitis must be treated by an ophthalmologist, and for recurrent episodes, adalimumab or infliximab are strongly preferred over etanercept to prevent future flares. 1

Acute Episode Management

Immediate Ophthalmology Referral

• Urgent ophthalmology evaluation is mandatory for all acute uveitis episodes to properly diagnose severity, evaluate for complications, and select appropriate local treatments 1
• Anterior uveitis (the most common type in AS, affecting 30-40% of patients) requires topical corticosteroids as first-line therapy 1, 2
• Topical prednisolone acetate or dexamethasone are the preferred corticosteroid formulations 3

Local Treatment Strategy

• Topical corticosteroids combined with cycloplegic agents form the foundation of acute anterior uveitis management 1, 4
• Posterior or panuveitis requires systemic corticosteroids in addition to local treatment, as these subtypes carry higher risk of sight-threatening complications including cystoid macular edema and vision loss 3, 2

Prevention of Recurrent Episodes

TNF Inhibitor Selection

For patients with recurrent uveitis requiring systemic therapy, adalimumab or infliximab should be used instead of etanercept 1

The evidence strongly supports this recommendation:

• Adalimumab and infliximab significantly reduce uveitis recurrence rates compared to etanercept in observational studies and pooled trial analyses 1
• Etanercept may paradoxically worsen or trigger new uveitis episodes in AS patients, with reports documenting increased risk compared to other TNF inhibitors 1, 5, 6
• A 2025 network meta-analysis confirmed adalimumab reduces recurrent uveitis risk by 30% compared to etanercept (RR: 0.70), while etanercept increased risk compared to golimumab and infliximab 5

At-Home Treatment for Recurrent Cases

• Patients with recurrent uveitis who are knowledgeable about symptoms should be prescribed topical glucocorticoids for prompt at-home initiation at the first sign of symptoms 1
• This approach must be coupled with a care plan requiring prompt ophthalmologic examination after self-initiation 1
• Early treatment reduces episode severity and decreases likelihood of ocular complications 1

Systemic Immunosuppression for Refractory Disease

When to Escalate Beyond Topical Therapy

• Moderate to severe intermediate uveitis, posterior uveitis, or panuveitis require systemic immunosuppression due to high risk of sight-threatening complications 2
• If inflammation cannot be controlled within 3 months or reactivates during corticosteroid taper, systemic immunomodulatory therapy is indicated 3

Treatment Hierarchy

First-line systemic therapy: Methotrexate is the preferred initial disease-modifying agent, achieving remission in approximately 52% of patients 3, 2

Second-line systemic therapy: For methotrexate-refractory cases, adalimumab is highly effective:

• Adalimumab extended time to treatment failure from 13 weeks (placebo) to 24 weeks and reduced treatment failure rates from 78.5% to 54.5% 7, 2
• FDA-approved for non-infectious uveitis based on two randomized controlled trials demonstrating significant reduction in treatment failure risk 7
• Infliximab provides similar efficacy, with complete remission in 30-85% of patients and rapid reduction in inflammation within 2 weeks 1

Critical Pitfalls to Avoid

The Etanercept Problem

Never use etanercept for AS patients with uveitis history 1, 3

• Multiple guidelines explicitly recommend against etanercept for uveitis management 3
• Case reports document severe, atypically aggressive uveitis developing in AS patients after etanercept initiation 4
• Two randomized trials showed etanercept provided no control of ocular inflammation or steroid-sparing effect compared to placebo 1

IL-17 Inhibitor Considerations

• Secukinumab and ixekizumab (selective IL-17A inhibitors) may increase uveitis risk and were less effective than placebo in recent analyses 1, 5
• Bimekizumab (dual IL-17A/IL-17F inhibitor) shows promise with the highest efficacy rankings in network meta-analysis, suggesting simultaneous inhibition of both pathways may be protective 5

Posterior Uveitis Warning

• Posterior uveitis can be asymptomatic yet still progress to irreversible vision loss, requiring aggressive treatment even without patient symptoms 3
• Regular ophthalmologic monitoring is essential to detect subclinical progression 3