133 B cell depletion therapy resulting in sustained remission of severe autoimmune complications following alemtuzumab treatment of multiple sclerosis

Introduction Alemtuzumab is a pan-lymphocyte ablating anti CD-52 monoclonal antibody licensed for the treatment of relapsing remitting multiple sclerosis (RRMS). Despite being classified as a high efficacy therapy, clinical application of alemtuzumab has been hampered by the frequent occurrence of secondary autoimmune disease (AID), with clinical trials and single-centre follow up cohorts estimating an incidence of up to 50% at seven years post treatment. Despite the establishment of pharmacovigilance programs to monitor for common complications of alemtuzumab, management guidelines for these conditions are lacking. Methods Here, we report a series of cases of female patients treated with alemtuzumab for RRMS who developed treatment refractory secondary AID complications; specifically acquired haemophilia A (AHA) and an autoimmune encephalitis (AIE). Results We report the sustained remission of these severe autoimmune disorders following administration of anti-CD20 therapy. This supports the current understanding of alemtuzumab associated AIDs, which occur in a time frame in which B-cell hyperpopulation and peripheral expansion occurs following initial lymphoablation. Conclusions Thus, we suggest that B-cell depletion should be initiated early in patients with severe, refractory complications of alemtuzumab. Furthermore, we suggest vigilant monitoring of patients with a preceding history of autoimmune thyroid disease following alemtuzumab treatment, as our experience suggests these patients have already demonstrated the potential to develop secondary AID.