1Gavin Giovannoni, 2Thomas Leist, 3Aida Aydemir, 3Elisabetta Verdun Di Cantogno
1Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; 2Division of Clinical Neuroimmunology, Jefferson University, Philadelphia, United States; 3EMD Serono Research & Development Institute, Inc. (an affiliate of Merck KGaA), Billerica, United States
CLASSIC-MS (NCT03961204) was an exploratory, ambispective Phase IV study designed to evaluate the long-term efficacy of cladribine tablets (CladT) in the real-world setting, for patients with relapsing multiple sclerosis (MS) who were previously enrolled to Phase III (parent) trials. The objective of this investigation was to report primary results for CLASSIC-MS in terms of long-term mobility and disability beyond the treatment courses that patients received in the parent trials, with the aim of informing future treatment approaches.
Material(s) and Method(s):
This analysis represents patients in CLASSIC-MS who participated in the Phase III CLARITY trial whether or not they participated in CLARITY Extension, and who had received ≥1 course of CladT or placebo. The primary objective of CLASSIC-MS was the evaluation of long-term mobility (no wheelchair use/bedridden; i.e. EDSS <7 in the 3 months prior to first visit in CLASSIC-MS). The main secondary objective was long-term disability status (no requirement for an ambulatory device; i.e. EDSS <6 any time since last parent study dose [LPSD]). Analyses are descriptive and shown in relation to exposed/never exposed to CladT in CLARITY.
The CLASSIC-MS population who previously participated in CLARITY/CLARITY Extension comprised 435 patients with relapsing MS (67.8% female; mean±SD EDSS score, 3.87±2.07 at CLASSIC-MS baseline), with a median time since LPSD of 10.9 (range 9.3–14.9) years and a median disease duration of 20.7 (range 13.9–46.5) years at CLASSIC-MS baseline. A total of 90.6% (n=394) were exposed to CladT during CLARITY/CLARITY Extension, including 160 patients who received the approved cumulative dose of 3.5 mg/kg over 2 years; the remaining 9.4% (n=41) were never exposed. The proportion of patients not using a wheelchair/bedridden in the 3 months prior to CLASSIC-MS (i.e. EDSS <7) was 90.0% of the CladT exposed cohort and 77.8% of the never exposed cohort. Regarding long-term disability status, the proportion of patients with no requirement for an ambulatory device (i.e. EDSS <6) was 81.2% of the CladT exposed and 75.6% of the never exposed cohorts, respectively.
Baseline patient characteristics suggest that patients enrolled in CLASSIC-MS were a representative sample of all patients included in the original parent studies. Reported findings for CLASSIC-MS, with a median of 10.9 years’ follow-up after CLARITY/CLARITY Extension, suggests sustained efficacy of CladT in terms of long-term mobility and disability status.