Is retinal vasculitis from Behçet's disease usually well controlled with Imuran (azathioprine)?

Azathioprine for Retinal Vasculitis in Behçet's Disease

Azathioprine combined with systemic corticosteroids is the established first-line treatment for retinal vasculitis in Behçet's disease, but "well controlled" is an overstatement—approximately 50% achieve complete remission, while the remainder require treatment escalation to biologics or other agents. 1, 2

Evidence for Azathioprine Efficacy

Guideline-Based Recommendations

Any patient with Behçet's disease and inflammatory eye disease affecting the posterior segment, including retinal vasculitis, should receive azathioprine (2.5 mg/kg/day) combined with systemic corticosteroids as initial therapy. 1, 3 This is a Level IB recommendation with Grade A strength from EULAR guidelines. 1

The landmark randomized controlled trial demonstrated that azathioprine:

• Decreased hypopyon uveitis attacks (NNT = 4) 1
• Stabilized visual acuity 1
• Decreased development of new eye disease (NNT = 2) 1
• Maintained beneficial effects over 7-year follow-up 1

Real-World Outcomes: The Reality Check

However, the clinical reality is more nuanced than guidelines suggest:

In a large cohort of 157 patients with severe uveitis from Behçet's disease treated with azathioprine plus corticosteroids, only 51.6% were complete responders, 41.4% were partial responders, and 7% were non-responders. 2 This means nearly half of patients do not achieve complete disease control with azathioprine alone.

Patients with retinal vasculitis specifically had significantly worse outcomes—they were 55% less likely to achieve complete remission (OR 0.45,95% CI 0.2-0.9, P=0.02) compared to those without retinal vasculitis. 2 This is the critical finding that directly answers your question: retinal vasculitis represents a more aggressive phenotype that responds less favorably to azathioprine monotherapy.

Additional Supporting Evidence

A retrospective study of 34 patients with retinal vasculitis (including 12 with Behçet's disease) found that azathioprine was:

• Most effective at reducing relapse rate (100% of evaluable patients showed decreased relapses) 4
• Only partially effective at reducing steroid dosage (60% achieved reduction) 4
• Maintained or improved visual acuity in 64% of eyes 4

When to Escalate Beyond Azathioprine

For severe eye disease—defined as >2 lines drop in visual acuity on a 10/10 scale and/or retinal vasculitis or macular involvement—treatment should be escalated to either cyclosporine A or infliximab in combination with azathioprine and corticosteroids. 1, 3

Alternative escalation options include:

• Interferon-alpha (with or without corticosteroids), which shows sustained responses and high remission rates 1, 3
• Monoclonal anti-TNF antibodies (infliximab or adalimumab), which demonstrate rapid response (1-5 days) and improvement in visual acuity 1, 3

Combination Therapy Approach

A longitudinal study of 295 patients followed for up to 10 years demonstrated that combination pulse cyclophosphamide plus azathioprine plus prednisolone achieved superior outcomes: 70% of eyes with retinal vasculitis improved, with mean retinal vasculitis scores decreasing from 3.0 to 1.4 (P<0.0001). 5 This suggests that for retinal vasculitis specifically, more aggressive initial combination therapy may be warranted rather than waiting for azathioprine monotherapy to fail.

Critical Pitfalls and Practical Considerations

Monitoring Requirements

• Regular ophthalmologic examinations are essential to detect early signs of disease progression 6
• Assess clinical symptoms and inflammatory markers (ESR, CRP) regularly 3
• Close monitoring for azathioprine toxicity, particularly myelosuppression when combined with other agents 7

Important Contraindications

• Never use cyclosporine A in patients with CNS involvement due to neurotoxicity risk 1, 8
• Screen for tuberculosis before initiating anti-TNF therapy, especially in endemic areas 3

Steroid Management

• Systemic corticosteroids should never be used alone in patients with posterior uveitis 1, 3
• Start with high-dose prednisolone (1 mg/kg/day) or IV methylprednisolone pulses (1g/day for 3-7 days) for acute attacks 3
• Taper by 5-10 mg every 10-15 days, aiming for maintenance dose of 5-10 mg/day 3

Prognostic Factors

Young males with early disease onset and retinal vasculitis have the highest risk of severe disease and poor outcomes—these patients may benefit from early aggressive immunosuppression or upfront combination therapy rather than sequential monotherapy. 3, 8, 2

Bottom Line for Clinical Practice

Azathioprine is the guideline-recommended first-line agent, but calling retinal vasculitis from Behçet's "usually well controlled" with azathioprine alone is optimistic. Approximately 50% will require treatment escalation, and those with retinal vasculitis at presentation are specifically at higher risk for incomplete response. 2 Have a low threshold for early escalation to biologics or combination therapy in patients with retinal vasculitis, particularly young males with aggressive disease. 1, 3, 5