Cladribine Data Show Low Overall Disability Accrual in MS, Supporting Early Initiation

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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REFERENCES
1. De Stafano N, Wiendl H, Barkhof F, et al. Low rate of progression independent of relapse in patients with relapsing multiple sclerosis treated with cladribine tablets. Presented at: ECTRIMS Congress; September 18-20, 2024; Copenhagen, Denmark. Poster P326.
2. De Stefano N, Achiron A, Barkhof F, et al. Effect of cladribine tablets on markers of disease progression, axonal loss, and oligoclonal bands in patients with relapsing multiple sclerosis: results from MAGNIFY-MS. Presented at: 2024 CMSC Annual Meeting; May 29-June 2; Nashville, TN. ABSTRACT DMT01.