In a Behçet's disease patient with retinal vasculitis who is taking azathioprine 150 mg daily, is prednisone still required or is azathioprine alone sufficient?

Management of Behçet's Disease with Retinal Vasculitis: Azathioprine Monotherapy vs. Combination with Prednisone

Azathioprine alone is insufficient for Behçet's disease with retinal vasculitis—systemic corticosteroids must be added during acute inflammatory attacks, though they should never be used as monotherapy. 1

Initial Treatment Approach

Any patient with Behçet's disease affecting the posterior segment requires immediate systemic immunosuppressive therapy, and glucocorticoids should never be used alone in patients with posterior uveitis. 1 The 2018 EULAR guidelines provide Grade A evidence that azathioprine is a first-line agent, but this recommendation explicitly states that systemic high-dose glucocorticoids are used for rapid suppression of inflammation during acute attacks. 1

Why Combination Therapy is Essential

• Azathioprine provides moderate efficacy with significant steroid-sparing effect, but requires approximately 4 months to achieve this steroid-sparing benefit. 1, 2
• During this lag period and during acute flares, systemic corticosteroids are necessary for rapid control of inflammation to prevent irreversible vision loss. 1
• Retinal vasculitis is the most aggressive ocular lesion in Behçet's disease and predicts worse systemic outcomes, necessitating aggressive initial treatment. 3

Practical Treatment Algorithm

Current Disease Activity Assessment

If the patient has active retinal vasculitis or posterior uveitis:

• Add high-dose systemic corticosteroids (typically prednisone 0.5-1 mg/kg/day) for rapid inflammation suppression 1, 3
• Continue azathioprine 150 mg daily (approximately 2-3 mg/kg) 3
• Taper corticosteroids gradually once inflammation is controlled 1

If the patient has been completely inactive for an extended period:

• Azathioprine monotherapy may be sufficient for maintenance 4
• However, close ophthalmologic monitoring every 3 months is mandatory 2
• Any sign of breakthrough inflammation requires immediate corticosteroid addition 1

Evidence Supporting Combination Therapy

Retrospective analysis of retinal vasculitis patients showed that azathioprine combined with systemic steroids was most effective at reducing relapse rate, though only partially effective in allowing steroid dose reduction. 4 This finding underscores that while azathioprine has steroid-sparing properties, complete steroid withdrawal may not be achievable in all patients.

Long-term studies using combination pulse cyclophosphamide, azathioprine, and prednisolone in 295 patients with active posterior uveitis and retinal vasculitis demonstrated significant improvement in all parameters, with 72% of patients showing overall improvement. 3 While this study used cyclophosphamide, it demonstrates the principle that azathioprine requires corticosteroid support for optimal outcomes.

Critical Pitfalls to Avoid

Never Use Corticosteroids Alone

Systemic immunosuppressives such as azathioprine must always accompany corticosteroids in posterior uveitis—corticosteroids alone are inadequate and associated with high relapse rates. 1, 5

Recognize Treatment Failure Early

• If disease remains uncontrolled despite azathioprine and corticosteroids, escalate to cyclosporine-A or monoclonal anti-TNF antibodies (infliximab or adalimumab) rather than increasing corticosteroid doses indefinitely. 1, 2, 6
• Infliximab provides rapid response with complete remission in 30-85.7% of refractory patients. 2
• Adalimumab has Grade A evidence for non-infectious uveitis and Grade B evidence specifically for Behçet's disease. 1, 2

Monitor for Azathioprine Limitations

• Approximately 17-24% of patients discontinue azathioprine within the first year due to ineffectiveness or adverse events. 1
• If breakthrough inflammation occurs on azathioprine 150 mg daily with corticosteroids, this represents treatment failure requiring escalation to biologics. 1, 6

Long-Term Steroid Tapering Strategy

Once inflammation is controlled, gradually taper prednisone while maintaining azathioprine. 1 The goal is to achieve the lowest effective corticosteroid dose or complete withdrawal, but this may take months and requires:

• Ophthalmologic examination every 3 months while on stable therapy 2
• Minimum 2 years of completely inactive disease off all topical steroids before considering tapering systemic immunosuppression 2
• Immediate corticosteroid reinitiation at any sign of recurrence 1

When Azathioprine Alone May Be Sufficient

Azathioprine monotherapy is only appropriate for patients who have achieved complete remission and have been stable for an extended period. 2, 4 Even in these cases, the patient must understand that corticosteroids will need to be restarted immediately if any inflammatory activity recurs.

The median time to achieve steroid-sparing effect with azathioprine is approximately 4 months, meaning most patients require at least this duration of combination therapy before attempting steroid withdrawal. 1, 2