Cladribine Data Show Low Overall Disability Accrual in MS, Supporting Early Initiation
Data from the MAGNIFY-MS study suggest that low 24-month PIRA rates across age groups and among those with or without treatment experience.
Letizia Leocani, MD
The results of an analysis of more than 250 patients with highly-active multiple sclerosis (MS) from the MAGNIFY-MS study (NCT03364036) suggest that treatment with cladribine (Mavenclad; EMD Serono) 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).1 This was particularly apparent among those who were treatment-naïve, suggesting that early initiation of the therapy is beneficial for optimized disease control.
Presented as a poster by Letizia Leocani, MD, an associate professor of neurology at Vita-Salute San Raffaele University, in Milan, Italy, and colleagues at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held September 18-20, in Copenhagen, Denmark, the data showed a PRIA-free rate of 93.3% (17 events) at month 24 based on Expanded Disability Status Scale (EDSS) scoring. Additionally, CDA-free and RAW-free rates were reported as 91.7% (21 events) and 98.4% (4 events) 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).
“In people with MS, early PIRA is associated with unfavorable long-term prognosis and disability accrual,” Leocani and colleagues wrote, adding that “previous assessment of PIRA were based on EDSS scores. However, inclusion of additional compositive measures provides a more comprehensive assessment of disease progression.”
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All told, the study 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).
Notably, Leocani and colleagues wrote that “T25W may be a convenient indicator of disease progression where full PIRA assessment is impractical,” as the data suggested that T25FW, as well as 6-month CDP, were the major contributors to composite PIRA. 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.
“At 24 months, the [Kaplan-Meier] estimated probability to be free of cPIRA was 85.0% overall,” Leocani and colleagues wrote, adding that it was 89% in the treatment-naïve group and 81.9% in the treatment-experienced group. “The probability of being free from cCDA was 89.0% for [treatment]-naïve and 77.9% for [treatment]-experienced” groups, and “no new safety signals were observed,” they concluded.
Earlier this year, additional data from MAGNIFY-MS were presented by Nicola De Stefano, MD, PhD, at the 2024 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held May 29-June 2, in Nashville, Tennessee. Those data showed that cladribine treatment increased rates of no evidence of disease activity (or NEDA) and progression, suggesting a substantial direct impact on central nervous system in highly active MS. Other markers of disease progression, axonal loss, and oligoclonal bands further confirmed these findings.2
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