Durable Clinical Improvements with Alemtuzumab in RRMS Patients in the Absence of Continuous Treatment: 7-Year Follow-up of Care-MS II (TOPAZ Study)

Thursday, May 31, 2018
Exhibit Hall A (Nashville Music City Center)
Barry A Singer, MD , MS Center for Innovations in Care, Missouri Baptist Medical Center, St. Louis, MO
Raed Alroughani, MD , Amiri Hospital, Sharq, Kuwait
Simon Broadley, MD , School of Medicine, Gold Coast Campus, Griffith University, Queensland, Australia
Hans-Peter Hartung, MD , Department of Neurology, Medical Faculty, Heinrich-Heine University, Dusseldorf, Germany
Eva Kubala Havrdova, MD, PhD , First Medical Faculty, Charles University in Prague, Prague, Czech Republic
Ho Jin Kim, MD , Research Institute and Hospital of National Cancer Center, Goyang, Korea, Republic of (South)
Celia Oreja-Guevara, MD , University Hospital San Carlos, Madrid, Spain
Carlo Pozzilli, MD , Sapienza University of Rome, Rome, Italy
Patrick Vermersch, MD , University of Lille, Lille, France
Sibyl Wray, MD , Hope Neurology MS Center, Knoxville, TN
Luke Chung, MD, MPH , Sanofi, Cambridge, MA
Nadia Daizadeh, PhD , Sanofi, Cambridge, MA
Madalina Chirieac, MD, MPH , Sanofi, Cambridge, MA
Krzysztof W Selmaj, MD , Medical University of Lodz, Lodz, Poland
on behalf of the CARE-MS II, CAMMS03409, and TOPAZ, Investigators , on behalf of the CARE-MS II, CAMMS03409, and TOPAZ Investigators, NJ

Background: In CARE-MS II (NCT00548405), alemtuzumab (12 mg/day, baseline: 5 days; 12 months later: 3 days) significantly improved clinical/MRI outcomes versus SC IFNB-1a over 2 years (y) in RRMS patients with inadequate response to prior therapy at baseline. Durable efficacy was observed in a 4-y extension (NCT00930553; 393/423 [93%] CARE-MS II patients enrolled, 338 [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. Further evaluation is ongoing (TOPAZ extension; NCT02255656).

Objectives: To evaluate efficacy/safety of alemtuzumab over 7 y (2 y of core study plus 4 y of extension and Y1 of TOPAZ) in patients initially randomized to alemtuzumab in CARE-MS II.

Methods: In TOPAZ, patients can receive alemtuzumab (12 mg/day on 3 consecutive days) retreatment ≥12 months apart or other DMTs at any time. MRI scans are performed annually. Assessments: annualized relapse rate (ARR); 6-month confirmed disability worsening (CDW); 6-month confirmed disability improvement (CDI); EDSS scores; no evidence of disease activity (NEDA; absence of clinical disease activity [relapses and 6-month CDW] and MRI disease activity [new Gd-enhancing T1 and new/enlarging T2 hyperintense lesions]); and AEs.

Results: Of the 336 patients who entered TOPAZ, 317 (94%) completed Y1 (Y7 after initiating alemtuzumab). ARR remained low (Y7: 0.14); 51% were relapse-free in Y3–7. The percentage of patients with improved/stable EDSS scores versus baseline remained high at Y7 (73% [improved, 22%; stable, 51%]). The mean change in EDSS score from baseline to Y7 was 0.17. At Y7, 69% were free of 6-month CDW; 44% achieved 6-month CDI. The majority of patients achieved NEDA each year (Y7: 60%). 47% received neither alemtuzumab retreatment nor other DMT, and 88% did not receive another DMT after the initial 2 courses. Overall AE incidence decreased over time. Thyroid AE incidence peaked in Y3 (17%) and then declined. 

Conclusions: Alemtuzumab efficacy was maintained for 7 y in patients who were initially randomized to alemtuzumab in CARE-MS II, despite 47% receiving no additional treatment since the initial 2 courses. 44% showed improvement in disability. Alemtuzumab safety profile remained consistent, with a decreased AE incidence over time. Alemtuzumab provides a unique treatment approach for RRMS patients, offering durable efficacy without continuous treatment.

Study Support: Sanofi and Bayer HealthCare Pharmaceuticals.