Abstract: We included three trials involving 1694 participants. All trials compared alemtuzumab 12 mg per day or 24 mg per day versus IFN beta 1a for treating RRMS. In CAMMS223, participants received either subcutaneous IFN beta 1a 44 μg three times per week or annual intravenous cycles of alemtuzumab (at a dose of 12 mg per day or 24 mg per day) for 36 months. In CARE-MS I and CARE-MS II, participants received subcutaneous IFN beta 1a 44 μg three times per week or annual intravenous cycles of alemtuzumab 12 mg per day for 24 months. All three studies were at risk of performance bias and attrition bias, one study was 'unclear' risk in selection bias. Compared with interferon beta 1a, alemtuzumab given at a dose of 12 mg per day probably reduces the risk of relapse (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.52 to 0.70, moderate quality evidence), may reduce the risk of worsening disability (RR 0.60, 95% CI 0.45 to 0.79, low quality evidence) and the risk of developing new T2 lesions on magnetic resonance imaging (RR 0.75, 95% CI 0.61 to 0.93, low quality evidence) after 24 and 36 months' follow-up. Mean Expanded Disability Status Scale (EDSS) scores may be similar between the treatment regimens (mean difference (MD) -0.35, 95% CI -0.73 to 0.03, low quality evidence). At a dose of 24 mg per day alemtuzumab may reduce relapse (RR 0.38, 95% CI 0.23 to 0.62, low quality evidence), worsening disability (RR 0.42, 95% CI 0.21 to 0.84, low quality evidence). The effects on EDSS scores when compared with interferon beta 1a at three years are uncertain due to the very low quality of evidence (MD -0.83, 95% CI -1.17 to -0.49). All three trials reported adverse events and serious adverse events. The risk of experiencing an adverse event in either alemtuzumab 12 mg or interferon groups may be similar (RR 1.03, 95% CI 0.98 to 1.08, low quality evidence). The risk of serious adverse events is probably similar between treatments (RR 1.03, 95% CI 0.82 to 1.29, moderate quality evidence). The risk of any adverse event may be similar between alemtuzumab 24 mg and interferon (RR 1.02, 95% CI 0.96 to 1.08, low quality evidence). The risk of serious adverse events is probably similar between treatments (RR 0.95, 95% CI 0.70 to 1.31, moderate quality evidence). Annual intravenous cycles of alemtuzumab at a dose of 12 mg per day probably reduces the proportion of participants who experience relapse, may reduce the proportion of participants who experience disability worsening and development of new T2 lesions on MRI over 2 to 3 years in comparison with subcutaneous IFN beta-1a 44 μg three times per week. Annual intravenous cycles of alemtuzumab at a dose of 24 mg per day may reduce the proportion of participants who experience relapse and disability worsening over 3 years in comparison with subcutaneous IFN beta-1a 44 μg three times per week. An average reduction of 0.8 EDSS units with alemtuzumab compared with interferon beta-1a was observed at a dose of 24 mg per day in one study. The rates of adverse events were similarly high for both treatments. The most frequently reported adverse events for both treatments were infusion-associated reactions, infections and autoimmune events. The use of alemtuzumab requires careful monitoring so that potentially serious adverse events can be treated early and effectively.

Plain-language summary: We searched medical databases and found three studies involving 1694 participants (CAMMS223, CARE-MS I and CARE-MS II). CAMMS223 involved people with previously untreated, early RRMS. Participants received either subcutaneous (under the skin) interferon beta 1a (at a dose of 44 μg) three times per week or annual intravenous (into a vein) courses of alemtuzumab (at a dose of either 12 mg per day or 24 mg per day) for 36 months. CARE-MS I enrolled adults aged 18 to 50 years with previously untreated RRMS. Participants received annual intravenous courses of alemtuzumab 12 mg per day or subcutaneous interferon beta 1a 44 μg three times per week for 24 months. CARE-MS II enrolled adults aged 18 to 55 years with RRMS and at least one relapse while on interferon beta or glatiramer (another medicine that alters the immune response) treatment. Participants received subcutaneous interferon beta 1a 44 μg three times per week, annual intravenous courses of alemtuzumab 12 mg per day or annual intravenous courses of alemtuzumab 24 mg per day for 24 months. The evidence is current to 1 February 2017. The review of trials found that, compared with subcutaneous interferon beta 1a three times per week, annual intravenous cycles of alemtuzumab probably reduces the proportion of participants who experience relapse, may reduce the proportion of participants who experience disability worsening and development of new T2 lesions on MRI. In one study, alemtuzumab 24 mg leads to slightly better EDSS scores when compared with interferon beta 1a. The rates of adverse events were similarly high for both treatments. The most frequently reported adverse events for both treatments were infusion-associated reactions, infections and autoimmune events. The use of alemtuzumab requires careful monitoring so that potentially serious adverse events can be treated early and effectively. The quality of the body of evidence obtained for each outcome is mainly low except for the number of participants experiencing at least one relapse for which the quality of evidence was moderate.