Abstract
Objective: To evaluate MRI lesion outcomes and brain volume loss (BVL) over 7 years (y) in alemtuzumab-treated CARE-MS II patients.
Background: In CARE-MS II (NCT00548405), alemtuzumab (12mg/day, baseline: 5 days; 12 months later: 3 days) significantly improved MRI outcomes, including BVL, versus SC IFNB-1a over 2 y in relapsing-remitting MS (RRMS) patients with inadequate response to prior therapy. Durable efficacy was observed in a 4-y extension (NCT00930553; 93% enrolled, 86% completed), in which patients could receive alemtuzumab retreatment as-needed for relapse/MRI activity or receive other disease-modifying therapies (DMTs) per investigator’s discretion. Patients completing the extension could enroll in TOPAZ (n=336), a 5-y study (NCT02255656), for further evaluation.
Design/Methods: In TOPAZ, patients can receive alemtuzumab retreatment (≥12 months apart) or other DMTs at any time (both per investigator’s discretion). Assessments: Annual MRI scored for disease activity (new Gd-enhancing lesions; new/enlarging T2 lesions), new T1 hypointense lesions, and BVL (derived by relative change in brain parenchymal fraction [BPF]).
Results: 317 patients (94%) completed Y1 of TOPAZ (Y7 after initiating alemtuzumab). At Y7, 67% of patients were free of MRI disease activity, 90% were free of new Gd-enhancing lesions, 67% were free of new/enlarging T2 lesions, and 88% had no new T1 hypointense lesions. Median BPF change from baseline to Y7 was −0.94%; median annual BPF change was reduced versus SC IFNB-1a over 2 y, remaining low in Y3–7 (Y3: −0.10%, Y4: − 0.19%, Y 5: −0.07%, Y6: −0.10%, Y7: −0.14%). 47% received no alemtuzumab retreatment or another DMT over 7 y.
Conclusions: Alemtuzumab durably reduced MRI disease activity and slowed BVL over 7 y in patients with inadequate response to prior therapy, despite 47% receiving no additional treatment after the initial 2 courses. Alemtuzumab may provide a unique treatment approach for RRMS patients, offering durable efficacy without continuous treatment.
Study Supported by: Sanofi and Bayer HealthCare Pharmaceuticals.
Disclosure: Dr. Pelletier has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Merck Serono, Novartis, Roche, and Sanofi. Dr. Pelletier has received research support from Biogen, Merck Serono, Novartis, Roche, and Sanofi. Dr. Traboulsee has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Chugai, F. Hoffmann-La Roche Ltd, Novartis, Sanofi Genzyme and Teva. Dr. Traboulsee has received research support from F. Hoffmann-La Roche Ltd. Dr. Barnett has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Novartis, and Sanofi, Medical Safety Systems. Dr. Comi has nothing to disclose. Dr. De Seze has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi. Dr. De Seze has received research support from Sanofi. Dr. Rovira has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer, Biogen, Bracco, Novartis, Sanofi, and Stendhal. Dr. Schippling has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Has received personal compensation for activities with Almirall, Biogen, Merck, Sanofi Genzyme, and TEVA. Dr. Margolin has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi. Dr. Chung has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi. Dr. Daizadeh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi. Dr. Nakamura has nothing to disclose. Dr. Arnold has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acorda, Biogen, F. Hoffmann-La Roche Ltd, MedDay, MedImmune, Mitsubishi, Novartis, Receptos/Celgene, Sanofi-Aventis. Dr. Arnold has received compensation for serving on the Board of Directors of NeuroRx Research.
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