302. ALEMTUZUMAB FOR RELAPSING AND REFRACTORY PRIMARY SYSTEMIC VASCULITIS – A TRIAL OF EFFICACY AND SAFETY (ALEVIATE): A RANDOMISED OPEN-LABEL PHASE II CLINICAL TRIAL

Abstract

Background: Granulomatosis with polyangiitis, microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis cause small vessel vasculitis (AAV). Behçet's disease (BD), one of primary systemic vasculitides (PSV), is a chronic relapsing inflammatory disease. Relapses and refractoriness to treatment are common to both diseases. There is an unmet need for safer therapy that leads to sustained treatment free remission in patients with S relapsing o on refractory disease. Alemtuzumab, anti‐CD52 antibody depletes lymphocytes for prolonged periods and it was shown to induce remission in refractory and relapsing vasculitis in some non‐RCT studies. Objectives: To determine the clinical response and severe adverse event rates associated with alemtuzumab among patients with refractory or relapsing PSV in a randomized clinical trial. Methods: A randomized, prospective, open label, dose ranging clinical trial. 24 patients with refractory and/or relapsing PSV were randomized to receive either high dose (60mg) or low dose (30mg) alemtuzumab at 0 and 6 months. Eligibility: Failure to respond to standard therapies such as cyclophosphamide or rituximab (in AAV) or anti‐TNF therapy in BD. Patients > 60 years, creatinine >150umol/L, severe infections, lymphopenia, pulmonary hemorrhage were excluded. Follow‐up: 12 months. Pre‐medications: 500mg of methylprednisolone. Antibiotic prophylaxis: co‐ trimoxazole and acyclovir for at least 3 months post‐therapy. Primary end‐point: i) Proportion of patients with treatment response at 6 months (Complete remission (CR) is defined as a BVAS/WG of 0 for at least one month. Partial response (PR) is the absence of severe BVAS/WG items and at least 50% fall in BVAS/WG score from baseline). ii) Proportion of patients with a severe adverse event. Results: See table Conclusion: In this phase II randomized controlled clinical trial testing the efficacy and safety of alemtuzumab to treat refractory and relapsing PSV, 65% of the patients achieved clinical remission at 6 months. Even though relapses were common, 35% achieved sustained remission in this difficult to treat group of patients. Serious adverse events were observed only in 26% of the patients. This study indicates that alemtuzumab is a safe therapy in a select group of refractory and/or relapsing patients with PSV.