PracticeUpdate Conference Series - ANZAN 2018

Efficacy of Alemtuzumab for Active RRMS is Maintained for 7 Years, in the Absence of Continuous Treatment Alemtuzumab efficacy was maintained for 7 years in treatment- naive patients with active relapsing-remitting multiple sclerosis (RRMS), despite 59% receiving no additional treatment since the initial two courses. In all, 37% of patients also showed improvement of disability.

T his finding of TOPAZ, the 5-year extension following the 4-year extension of the 2-year Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis, study I (CARE-MS I) trial, was reported at ANZAN 2018. Pamela A. McCombe, MD, of the University Of Queensland in Brisbane, QLD, explained that in CARE-MS I, alemtuzumab 12 mg daily (baseline, 5 days; 12 months later, 3 days) improved clinical/MRI outcomes vs subcutaneous interferon ß-1a over 2 years in patients with treatment-naive RRMS. Efficacy was durable in a 4-year extension (95% enrolled, 92% completed), wherein patients could receive as-needed alemtuzumab retreatment for relapse/MRI activity or other disease-modifying thera- pies per investigator’s discretion. Patients completing the extension could enroll in the 5-year TOPAZ study for further evaluation. Dr. McCombe and colleagues set out to examine efficacy and safety through year 7 in patients treated with alemtuzumab from CARE-MS I. In TOPAZ, patients can receive alemtuzumab retreat- ment (≥12 months apart) or other disease-modifying therapies (both per investigator discretion). MRI scans are performed annually. Assessments are annualized relapse rate; stable/ improved Expanded Disability Status Scale (EDSS) score from core study baseline; 6-month confirmed worsening of disability; 6-month confirmed improve- ment in disability; no evidence of disease activity; and adverse events. A total of 299 of 321 patients (93%) completed TOPAZ year 1 (year 7 after initiating alemtuzumab). Annualized relapse rate remained low (year 7: 0.13). A total of 60% were relapse-free in years 3–7.

The percentage of patients with stable or improved EDSS score remained high (year 7: 78%). Through year 7, 74% were free from 6-month con- firmed worsening of disability. In all, 37% achieved 6-month confirmed disability improvement, and the majority achieved no evidence of disease activity each year (year 7: 61%). Overall, 59% received no additional treatment (alemtuzumab or other disease-modifying therapy) after the initial two courses. Overall incidence of adverse events, infusion-asso- ciated reactions, and infections decreased over time. The incidence of thyroid adverse events peaked in year 3 (15%) and then declined. Dr. McCombe concluded that alemtuzumab effi- cacy was maintained for 7 years in treatment-naive patients with active RRMS, despite 59% receiving no additional treatment since the initial two courses. In all, 37% of patients also showed improvement in disability. The alemtuzumab safety profile remained consistent. The overall incidence of adverse events decreased over time. Alemtuzumab may provide a unique treatment approach for patients with relapsing-remitting multi- ple sclerosis. It offers durable efficacy in the absence of continuous treatment. Richard AL Macdonell, MD, of Austin Health and the Florey Institute of Neuroscience and Mental Health in Melbourne, Victoria, and colleagues set out to examine improvement in disability in each functional system in alemtuzumab-treated patients with active RMS in the CARE-MS II extension. Dr. Macdonell explained that in CARE-MS II, alemtu- zumab (12 mg daily, baseline: 5 days; 12 months later: 3 days) improved clinical/MRI outcomes significantly

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