Durable Improvements in Relapse and Disability Outcomes over 7 Years with Alemtuzumab in CARE-MS II Patients: Results from the TOPAZ Study

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Singer, Barry A
Alroughani, Raed
Brassat, David
Broadley, Simon
Hartung, Hans-Peter
Havrdova, Eva
Kim, Ho Jin
Oreja-Guevara, Celia
Pozzilli, Carlo
Selmaj, Krzysztof W
Vermersch, Patrick
Wray, Sibyl
Margolin, David H
Daizadeh, Nadia
et al.
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San Diego, CA, USA


Background: In CARE-MS II (NCT00548405), 2 courses of alemtuzumab demonstrated significantly greater improvements on clinical outcomes vs SC IFNB-1a over 2 years (y) in patients (pts) with active RRMS and inadequate response to prior therapy. Alemtuzumab pts who were followed for a further 4 y in an extension study (NCT0090553) showed durable efficacy, even though most received no additional alemtuzumab or other disease-modifying therapy (DMT). In CARE-MS II, pts received 2 courses of alemtuzumab 12 mg/day (baseline: 5 days; 12 months [mo] later: 3 days); in the extension, pts could receive as-needed alemtuzumab retreatment (12 mg/day on 3 consecutive days; ≥12 mo after previous course for relapse or MRI activity) or another DMT (per investigator discretion). Pts completing the extension could enroll in the 5-y TOPAZ study (NCT02255656) for further long-term evaluation.

Objectives: Evaluate efficacy and safety of alemtuzumab in CARE-MS II pts over 7 y.

Methods: In TOPAZ, pts can receive alemtuzumab retreatment ≥12 mo after previous course or another DMT at any time (both per investigator discretion); MRI scans are done annually. Assessments included: annualized relapse rate (ARR); proportions of relapse-free pts; 6-mo confirmed disability worsening (CDW); 6-mo confirmed disability improvement (CDI); no evidence of disease activity (NEDA); adverse events (AEs).

Results: 338/393 (86%) CARE-MS II alemtuzumab-treated pts who entered the extension remained on study until end of Y6. 336 then entered TOPAZ; 317 (94%) remained on study through Y7. Low ARR was maintained (0.14 at Y7). 87% of pts were relapse-free in Y7. Proportion of pts with stable or improved EDSS remained high (Y7: 73%). Through 7 y, 69% of pts were free of 6-mo CDW, 44% experienced 6-mo CDI, and the majority achieved NEDA in each year. These effects were achieved with 47% of pts receiving no further treatment (alemtuzumab or another DMT) after their initial 2 alemtuzumab courses. Incidences of most AEs, infusion-associated reactions, and infections decreased over time and were reduced vs the 2-y core study. Thyroid AE incidence peaked at Y3, then declined through Y7.

Conclusion: Clinical efficacy of alemtuzumab was durable for 7 y in pts who had inadequate response to prior therapy, despite 47% receiving no further treatment since the initial 2 alemtuzumab courses. The majority of pts maintained low ARR, were relapse-free, showed stabilized or improved disability, and achieved NEDA in each year.

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Multiple Sclerosis Journal

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Singer, BA; Alroughani, R; Brassat, D; Broadley, S; Hartung, H-P; Havrdova, E; Kim, HJ; Oreja-Guevara, C; Pozzilli, C; Selmaj, KW; Vermersch, P; Wray, S; Margolin, DH; Daizadeh, N; et al., Durable Improvements in Relapse and Disability Outcomes over 7 Years with Alemtuzumab in CARE-MS II Patients: Results from the TOPAZ Study, Multiple Sclerosis Journal, 2018, 24, pp. 22-22