What is the efficacy of Imuran (Azathioprine) for treating Behcet's disease?

Efficacy of Azathioprine (Imuran) for Behçet's Disease

Azathioprine is an effective immunosuppressive agent for several manifestations of Behçet's disease, particularly for posterior segment eye involvement, gastrointestinal involvement, and neurological involvement, and should be considered a cornerstone therapy for moderate to severe disease. 1

Efficacy by Organ System

Eye Involvement

• Any patient with Behçet's disease and inflammatory eye disease affecting the posterior segment should be on a treatment regimen that includes azathioprine and systemic corticosteroids 1, 2
• For severe eye disease (defined as >2 lines drop in visual acuity or retinal disease), azathioprine should be combined with either cyclosporine A or infliximab for better outcomes 2, 3
• Early treatment with azathioprine may have a protective effect in patients with isolated anterior uveitis who have risk factors for progression (young age, male sex, early disease onset) 1

Neurological Involvement

• Acute attacks of parenchymal nervous system involvement should be treated with high-dose glucocorticoids followed by slow tapering, together with immunosuppressives such as azathioprine 1
• Azathioprine is recommended for long-term management after initial control of neurological symptoms to prevent recurrence 1
• Cyclosporine A should be avoided in patients with neurological involvement due to potential neurotoxicity 1

Gastrointestinal Involvement

• Azathioprine is recommended for moderate to severe gastrointestinal involvement in Behçet's disease 1
• For refractory/severe gastrointestinal involvement, glucocorticoids should be considered during acute exacerbations together with disease-modifying agents such as azathioprine 1
• Medical treatment with azathioprine should be tried before surgery, except in emergencies such as perforation, major bleeding, or obstruction 1

Vascular Involvement

• For the management of acute deep vein thrombosis in Behçet's disease, azathioprine is one of the recommended immunosuppressive agents 1
• Azathioprine may help prevent post-thrombotic syndrome, which is frequent with recurrent deep vein thrombosis 1

Joint Involvement

• For recurrent and chronic arthritis in Behçet's disease, azathioprine is recommended when colchicine is ineffective 1
• Azathioprine can be considered as a second-line agent after colchicine for joint manifestations 2

Clinical Evidence and Efficacy Rates

• A study specifically evaluating Imuran (azathioprine) in Behçet's disease found that daily administration of 50-75 mg over a period of 1 year alleviated ocular symptoms in 16% of patients, was slightly effective in 20%, and ineffective in 64% 4
• Azathioprine was also found to alleviate extraocular pathology, such as stomatitis, erythema, and arthralgia 4
• Compared to other immunosuppressives like chlorambucil (Leukerin), azathioprine has a better safety profile and can be prescribed for longer periods 4, 5

Dosing and Administration

• The typical dosage of azathioprine for Behçet's disease is 2.5 mg/kg/day 2
• When used for posterior uveitis, azathioprine is typically combined with systemic corticosteroids 2, 3
• For neurological involvement, azathioprine is used alongside high-dose glucocorticoids (typically starting with intravenous methylprednisolone pulses followed by oral prednisolone at 1 mg/kg/day) 1

Limitations and Considerations

• In some severe or refractory cases, azathioprine may be insufficient, requiring escalation to biological agents such as TNF-alpha inhibitors 1
• For ocular disease refractory to conventional immunosuppressants including azathioprine, interferon alpha-2a has shown promising results 6
• Regular monitoring of complete blood count and liver function tests is necessary during azathioprine therapy 2
• A combination-agent regimen is generally more effective than azathioprine monotherapy for severe manifestations 7

Treatment Algorithm

1. For mild mucocutaneous and joint manifestations:

   • Start with colchicine (first-line) 1
   • If inadequate response, add or switch to azathioprine 1, 2

2. For posterior segment eye involvement:

   • Start azathioprine (2.5 mg/kg/day) plus systemic corticosteroids 1, 2
   • For severe eye disease, add cyclosporine A or infliximab 2

3. For neurological involvement:

   • High-dose glucocorticoids plus azathioprine 1
   • For refractory cases, consider TNF-alpha inhibitors 1

4. For gastrointestinal involvement:

   • Mild: 5-ASA derivatives 1
   • Moderate to severe: Azathioprine plus glucocorticoids during exacerbations 1
   • Refractory: Consider TNF-alpha inhibitors or thalidomide 1

5. For vascular involvement:

   • Deep vein thrombosis: Azathioprine plus glucocorticoids 1
   • Refractory venous thrombosis: Consider TNF-alpha inhibitors 1