A new study presented at ECTRIMS 2024 revealed that 80% of patients with relapsing multiple sclerosis had an estimated no evidence of disease activity rate at both 3 and 4 years when discontinuing cladribine tablets.
Nicola De Stefano, MD, PhD
New findings from the follow-up extension of the MAGNIFY-MS study presented at the 2024 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, held September 18-20, in Copenhagen, Denmark, confirmed the long-term efficacy of cladribine (Mavenclad; EMD Serono) tablets among patients with relapsing multiple sclerosis (MS) over a 4-year treatment period.1
Among 219 patients who enrolled in the extension study (women, 64.8%; mean age, 40.4 years; treatment-naïve, 40.6%; MRI lesions [baseline period]: T1 Gd+, 50.2%; active T2, 42.9%), the Kaplan-Meier estimated no evidence of disease activity (NEDA-3) rate was 78.6% (95% CI, 72.5-83.5) at 3 years and 79.2% (95% CI, 72.3-84.6) at 4 years. Notably, the estimated NEDA-3 rate for years 3 and 4 combined was 54.2% (95% CI, 47.3-60.7; crude event rates for individual components, free from relapse, 80.8%; 6-month confirmed disability progression [6MCDP], 84.5%; MRI activity, 53.0%).
In the MAGNIFY-MS Extension, patients were included if they received at least 1 dose of cladribine tablets in MAGNIFY-MS (NCT03364036), a previously completed phase 4 study of 270 participants with highly active relapsing MS, and had MRI data available from 18 or 24 months of the parent study. Additionally, patients were required to have 24-month data on the Expanded Disability Status Scale (EDSS) and relapse activity. Researchers noted that visits occurred at 36 months and 48 months. Per European Union label, investigators did not schedule participants to receive cladribine tablets in the 3- or 4-years following treatment initiation.
Presented by lead author Nicola De Stefano, MD, PhD, professor of neurology in the department of medicine, surgery, and neuroscience at the University of Siena in Italy, and colleagues, the primary end point of the analysis was the proportion of patients with NEDA-3 at 3 and 4 years combined which authors defined as no qualifying relapses, no 6MCDP, and no new T1 Gd+ and/or active T2 MRI lesions. Investigators analyzed data for all participants combined and noted that the subgroups analyzed included patients who were treatment-naïve and treatment-experienced.
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Among the 219 patients enrolled, the annualized qualified relapse rate (ARR) was 0.09 (95% CI, 0.06-0.12) for the parent study and 0.08 (95% CI, 0.06-0.11) for the extension period. Additional findings showed that the ARR was 0.09 (95% CI, 0.07-0.11) over 4 years with cladribine tablets. De Stefano and colleagues noted that these produced efficacy results were consistent with the results observed in the treatment-naïve and treatment-experienced subgroups.
In terms of safety, investigators observed that 142 patients (64.8%) reported at least 1 adverse event (AE) during the extension study, with 94.4% of these considered mild to moderate in severity. Additionally, authors noted that 13 patients had at least 1 serious AE (5.9%), and 3 of the patients had at least 1 any serious treatment-related AE (1.4%). Overall, researchers reported that the long-term safety profile of cladribine tablets was consistent with earlier safety data, showing no new safety signals observed.
An additional analysis from MAGNIFY-MS presented at ECTRIMS 2024 suggested that treatment with cladribine tablets results in low overall disability accrual, as measured by progression independent of relapse activity (PIRA), relapse-associated worsening (RAW), and confirmed disability accumulation (CDA).2 Presented by lead author De Stafano and colleagues, the data showed a PRIA-free rate of 93.3% (17 events) at month 24 based on EDSS scoring. Additionally, CDA-free and RAW-free rates were reported as 91.7% (21 events) and 98.4% (4 events), respectively, at 24 months.
When exploring the composite PIRA score—defined as the presence of 6-month confirmed disability progression (CDP), or 20% confirmed progression on either the timed 25-foot walk test (T25FW) or 9-hole peg test (9HPT)—the rates of freedom from cPIRA progression were still high, at 85% (38 events). When considering the composites of CDA and RAW freedom, rates were similarly high, at 82.7% (44 events) and 97.3% (7 events).
All told, the analysis included 270 patients, of whom 117 were treatment-naïve and 153 were treatment-experienced. Of the full cohort, 66.7% (n = 180) were women, and the mean age was 37.7 years (SD, 9.8). There were 66 patients (24.4%; 28 treatment-naïve, 38 treatment-experienced) who had a baseline EDSS score above 3, and the mean time since disease onset was 7.1 years (SD, 7.1) for the full cohort (3.7 [SD, 4.6] for treatment-naïve, 9.7 [SD, 7.6] for treatment-experienced).
In total, 17 patients met the criteria for composite PIRA on T25FW, 13 of whom were those with prior treatment experience; and when considering progression by age group, T25FW was a major contributor for those both under the age of 40 years (12 of 26) and over (5 of 12). Six-month CDP was a contributor of similar import, with 17 patients in the full cohort meeting those criteria, and similar numbers to those of T25FW across age groups (under 40: 11 of 26; over 40: 6 of 12). The 9HPT had a smaller contribution across these assessed subgroups.
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