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Introduction Alemtuzumab is a potent disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS).Objective Describe real-world outcomes following alemtuzumab treatment and current treatment strategies for breakthrough relapse.Methods Using the international MSBase registry plus two UK centres (Cardiff, Cambridge), we studied patients with RRMS who received at least 2 cycles of alemtuzumab and at least 1 follow-up visit.Results We included 1,663 patients (median pre-treatment relapse rate = 1/year; median pre-treatment disability (EDSS) score 3; median follow-up from baseline of 6 (range 1-21) years). 1,101 (66%) remained relapse-free and required no further treatment, 445 (27%) experienced a breakthrough relapse, 95 received further treatment despite not relapsing (6%, likely due to unrecorded MRI activity), and 22 converted to clinician-defined secondary progressive MS (1%). Following breakthrough relapse, 230 patients (52%) received further treatment including alemtuzumab 3rd cycle (153; 67%), ocrelizumab (42; 18%) and natalizumab (10; 4%). At last follow-up, median EDSS score had improved to 2.5.Conclusion Two thirds of patients remain relapse- and treatment-free 6 years after alemtuzumab, consistent with phase III extension studies. Patients who do relapse typically receive a third cycle of alemtuzumab or a different high potency therapy. Inadequate numbers precluded robust inference about either strategy’s effectiveness.wb255@cam.ac.uk