Cladribine Slows Disability Accumulation in Treatment-Naïve or -Experienced MS

Over 24 months, treatment with cladribine tablets leads to slower disability accrual in both treatment-naïve and treatment-experienced multiple sclerosis (MS), according to study results presented at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in Copenhagen, Denmark, from September 18 to 20, 2024.

Disability accumulation in MS occurs through both progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW).

For the MAGNIFY-MS study (ClinicalTrials.gov Identifier: NCT03364036), researchers recruited patients (N=270; mean age, 37.7; women, 66.7%) with MS who were treatment-naïve (n=117) or treatment-experienced (n=153). The researchers evaluated the effect of cladribine on PIRA, RAW, and confirmed disability accumulation (CDA).

Six-month confirmed PIRA was defined as no relapse within 90 days of a progressive event defined using the Expanded Disability Status Scale (EDSS); composite PIRA was defined as 6-month confirmed disability progression or 20% progression in either the timed 25-foot walk (T25FW) or 9-hole peg test; composite RAW was defined as any event within 90 days of a relapse; and composite CDA was defined as any composite PIRA or composite RAW event.

In the year before initiating cladribine, among patients who had treatment-naïve vs treatment-experienced MS:

• 85.5% vs 42.5% had 2 or more relapses,
• 49.6% vs 51.0% had 1 or more T1 gadolinium-enhancing lesions, and
• 23.1% vs 26.8% had 1 or more new T2 lesions.

At 24 months of cladribine treatment, the pooled rate of CDA was 7.8%, PIRA was 6.3%, RAW was 1.5%, composite CDA was 16.3%, composite PIRA was 14.1%, and composite RAW was 2.6%.

Stratified by treatment history, the rate of disability accrual was lower in treatment-naïve MS vs treatment experienced MS.

In the treatment-naïve group, all 3 components of composite PIRA contributed equally to the observed rate. Conversely, 6-month confirmed disability progression and T25FW contributed more to the composite PIRA rate among patients who were treatment-experienced.

The estimated rate of freedom from composite PIRA at 24 months with cladribine was 89.0% for patients who were treatment-naïve and 81.9% patients who were treatment-experienced and freedom from composite CDA was 89.0% and 77.9%, respectively.

No new safety signals associated with cladribine were identified in this study.

These analyses were not prespecified in the MAGNIFY-MS study, and all findings should be considered as exploratory.

“These results indicate low overall disability accrual in highly active [cladribine]-treated [people with] MS. [Treatment]-naive [people with] MS had consistently lower PIRA, RAW, and CDA, supporting the benefit of early initiation of [cladribine] on slowing overall disability accumulation,” the researchers concluded.

Disclosure: This research was supported by Merck. Please see the original reference for a full list of disclosures.