Alemtuzumab Controlled Clinical and MRI Outcomes and Slowed Brain Volume Loss in RRMS Patients: 8-Year Follow-up of CARE-MS II Patients (TOPAZ study)

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Singer, Barry A
Alroughani, Raed
Broadley, Simon
Eichau, Sara
Hartung, Hans-Peter
Havrdova, Eva K
Kim, Ho Jin
Nakamura, Kunio
Navas, Carlos
Pozzilli, Carlo
Rovira, Alex
Vermersch, Patrick
Wray, Sibyl
Chung, Luke
et al.
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Dallas, TX, USA


Background: In the 2-year (y) CARE-MS II phase 3 trial (NCT00548405), alemtuzumab (12 mg/day; baseline: 5 consecutive days; 12 months later: 3 consecutive days) significantly improved clinical and MRI outcomes versus SC IFNB-1a in RRMS patients with inadequate response to prior therapy. In a 4-y extension (NCT00930553), patients could receive additional courses of alemtuzumab (12 mg/day on 3 consecutive days; ⩾12 months apart) as needed for disease activity or receive other disease-modifying therapy (DMT) per investigator’s discretion. Efficacy on clinical/MRI outcomes was maintained through Y6, with 50% receiving no additional alemtuzumab or other DMTs in the extension. Following the initial 4-y extension, patients could continue in TOPAZ (NCT02255656), an additional 5-y extension study, for further evaluation.

Objectives: To evaluate 8-y efficacy and safety outcomes in alemtuzumab-treated CARE-MS II patients.

Methods: At the investigator’s discretion, patients in TOPAZ can receive additional as-needed alemtuzumab (⩾12 months apart; no criteria) or receive other DMT (at any time).

Results: Of 435 alemtuzumab-treated CARE-MS II patients, 300 (69%) completed 8-y total follow-up; 44% received neither additional courses of alemtuzumab nor another DMT. Of 393 patients who entered the extension, 200 (51%) received ⩾3 courses of alemtuzumab (3 courses, 29%; 4 courses, 16%; 5 courses, 3%, >5 courses, 3%). Course 3 was given in Y3 (20%), Y4 (11%), Y5 (9%), Y6 (5%), Y7 (2%), and Y8 (3%). In Y8, the annualized relapse rate was 0.18, with 85% of patients relapse-free. Compared with core study baseline, 70% of patients had stable/improved EDSS scores at Y8, and mean change in EDSS score was 0.17. Over 8 y, 64% of patients were free of 6-month confirmed disability worsening, and 47% had 6-month confirmed disability improvement. In Y8, 58% of patients achieved no evidence of disease activity, and 70% were free of MRI disease activity. Median percent cumulative brain volume loss (BVL) from baseline through Y8 was −1.06%; median annual BVL from Y3 to Y8 was ⩽−0.19%. The safety profile in Y8 was consistent with the previous years; incidence of AEs, infections, and thyroid AEs continued to decline. No new cases of immune thrombocytopenia or nephropathy were seen.

Conclusion: Alemtuzumab efficacy on clinical, MRI, and BVL outcomes was maintained over 8 y, with 44% of CARE-MS II patients receiving no additional treatment. Safety was consistent and manageable through Y8.

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Multiple Sclerosis Journal

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Singer, BA; Alroughani, R; Broadley, S; Eichau, S; Hartung, H-P; Havrdova, EK; Kim, HJ; Nakamura, K; Navas, C; Pozzilli, C; Rovira, A; Vermersch, P; Wray, S; Chung, L; et al., Alemtuzumab Controlled Clinical and MRI Outcomes and Slowed Brain Volume Loss in RRMS Patients: 8-Year Follow-up of CARE-MS II Patients (TOPAZ study), Multiple Sclerosis Journal, 2019, 25, pp. 45-45