Treatment of mucocutaneous manifestations in Behcet's disease with anakinra: a pilot open-label study

Background: The effect of IL-1 blocking therapy on mucocutaneous manifestations of Behcet's disease is incompletely understood. Methods: Six patients with Behcet's disease and ongoing oral/genital ulcers for >= 1 month were enrolled into an adaptive, two-phase clinical trial and included in the analysis. Study duration was 6 months with extension up to 16 months. All were treated non-blinded with anakinra 100 mg subcutaneous daily with the option to escalate the dose to 200 mg in partial responders after 1 month and 300 mg after 6 months. Patients recorded the number and severity of ulcers in daily diaries. The primary outcome was remission defined as no ulcers on physical exam for two consecutive monthly visits between months 3 and 6. Secondary outcomes included the number and severity of patient-reported ulcers, patient/physician global scores, and standardized disease activity scores. Results: Two of six patients achieved the primary outcome. Five of six patients had improvement in the number and severity of ulcers. Non-statistically significant improvements were seen in secondary outcomes. Over the entire study, patients reported >= 1 oral and >= 1 genital ulcer on 665 (66%) and 139 (14%) days, respectively. On anakinra 200 mg vs 100 mg, patients reported fewer days with oral ulcers (65% vs 74% of days, p = 0.01) and genital ulcers (10% vs 22% of days, p < 0.001) and milder oral ulcer severity (p < 0.001). Increase of anakinra to 300 mg did not result in further improvements. Adverse events were notable for mild infections. Conclusion: Anakinra at an optimal dose of 200 mg daily had an acceptable safety profile and was partially effective in the treatment of resistant oral and genital ulcers in Behcet's disease.