What is the first-line therapy for uveitis due to Behçet disease?

Treatment for Behçet Uveitis

For Behçet disease uveitis affecting the posterior segment, immediate systemic immunosuppression with azathioprine or cyclosporine-A should be initiated as first-line therapy, with monoclonal anti-TNF antibodies (infliximab or adalimumab) reserved for refractory cases or as early therapy in severe disease. 1

Initial Management Strategy

Corticosteroids for Acute Control

• High-dose systemic corticosteroids should be added for rapid control during acute attacks, but never used as monotherapy for posterior segment disease 1
• Topical corticosteroids (prednisolone acetate or dexamethasone) are appropriate for anterior chamber inflammation but insufficient alone for posterior involvement 1
• Intravitreal corticosteroid injections may serve as adjunctive therapy for acute exacerbation in one eye, but never as standalone treatment 1

First-Line Systemic Immunosuppression

The American College of Rheumatology provides Grade A recommendations for azathioprine and cyclosporine-A as initial systemic therapy for posterior segment Behçet uveitis 1:

• Azathioprine demonstrates moderate efficacy with significant steroid-sparing effect, with only 2% of patients discontinuing due to adverse effects 2
• Cyclosporine-A combined with low-dose corticosteroids reduces both frequency (p<0.01) and severity (p<0.01) of ocular attacks compared to conventional therapy 3
• Visual acuity improved or remained stable in 75.7% of eyes with combined cyclosporine-prednisone therapy 1

Biologic Therapy for Refractory Disease

Anti-TNF Monoclonal Antibodies

When first-line therapy fails or in severe presentations, monoclonal anti-TNF antibodies provide superior outcomes 1:

• Infliximab (5 mg/kg at weeks 0,2,6, and 14) achieves complete remission in 30-85.7% of patients, with rapid response within 2 weeks 1
• In patients resistant to azathioprine-cyclosporine-corticosteroid combination, infliximab significantly reduced mean uveitis attacks and corticosteroid doses during the infusion period 4
• Adalimumab receives a Grade B recommendation for noninfectious uveitis, with evidence supporting its use in Behçet disease 2

Interferon Therapy

Interferon alfa-2a represents an effective alternative with Grade B recommendation 2:

• Reduces relapse rate from 1.39-3.61 relapses/person/year to 0.05-0.8 relapses/person/year 2
• Visual acuity improved or remained stable, with resolution of macular edema in all affected patients 2
• Achieves significant steroid-sparing effect when administered subcutaneously without concomitant steroids 2

Treatment Algorithm

Step 1: Immediate Initiation (Week 0)

• Start azathioprine or cyclosporine-A immediately for new-onset posterior segment or panuveitis 1
• Add high-dose systemic corticosteroids for acute attack control 1
• Arrange urgent ophthalmology evaluation to assess severity and complications 1

Step 2: Early Assessment (Weeks 2-12)

• If inflammation cannot be controlled within 3 months, escalate to biologic therapy 1
• If reactivation occurs during steroid dose reduction, add or switch to anti-TNF therapy 1
• Consider earlier biologic initiation in cases with macular edema, retinal infiltrates, or poor prognostic factors 1

Step 3: Refractory Disease Management

• Infliximab or adalimumab should replace (not supplement) failed conventional immunosuppression 4
• Combination therapy with azathioprine plus anti-TNF may improve outcomes, though caution is advised for potential interactions 1
• Evidence suggests potential therapeutic role for biologics earlier in Behçet disease compared to other uveitis etiologies 5

Critical Pitfalls to Avoid

Medication Selection Errors

• Never use etanercept for Behçet uveitis, as it lacks efficacy and may paradoxically worsen inflammation 2
• Subcutaneous secukinumab is not supported for Behçet disease with active or quiescent uveitis, showing no significant reduction in inflammatory attacks 2
• Avoid corticosteroid monotherapy beyond 6-12 months due to severe adverse effects 6

Monitoring and Duration Failures

• Delayed diagnosis and treatment initiation significantly worsen prognosis, requiring aggressive early intervention 1
• Ophthalmologic examination every 3 months is mandatory while on stable systemic therapy 1
• Maintain immunosuppression for minimum 2 years of completely inactive disease off all topical steroids before considering tapering 1

Long-Term Management Considerations

Treatment Duration

• Drug-free remission is achievable after successful anti-TNF treatment combined with azathioprine for 2 years 1
• The median time to steroid-sparing effect with azathioprine is 4 months 2
• Most infliximab-related uveitis attacks (76.9%) occurred at weeks 14 or 22, suggesting need for maintenance dosing adjustments 4

Prognostic Factors

• Hypopyon, vitreous "snowball" opacities, macular edema, and retinal infiltrates during acute attacks are associated with poor visual outcomes 1
• Complete remission rates of 30-85.7% are achievable with infliximab, with visual acuity improvement or stabilization in the majority of treated eyes 1
• Combination therapy with cyclosporine-corticosteroids maintained or improved visual acuity in 90.9% of eyes 3