Switch to Cladribine From Natalizumab Maintains Disease Stability in Relapsing MS

Patients with relapsing multiple sclerosis (MS) who switch to cladribine tablets from natalizumab have preserved disease stability and reduced relapse rates, according to study results presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2025, held in West Palm Beach, Florida from February 27 to March 1, 2025.

Researchers conducted the open-label, phase 4 CLADRINA trial (ClinicalTrials.gov Identifier: NCT04178005) to assess the safety, efficacy, and lymphocyte dynamics following the switch from natalizumab to cladribine. The current 24-month analysis included 40 patients with relapsing MS who transitioned to cladribine within 4 weeks of their final natalizumab infusion.

The primary outcome focused on changes in CD3+ T lymphocytes, CD19+ B lymphocytes, and dendritic cells at 12 and 24 months, with additional evaluations of annualized relapse rates (ARRs), Expanded Disability Status Scale (EDSS) scores, and magnetic resonance imaging (MRI)-based disease activity.

The study participants had a mean (SD) age of 41.3 (10.2) years, with women comprising 70% of the group.  Most patients switched to cladribine due to positive John Cunningham virus titers, with a mean transition time of 12.2 days (range, 3.0 to 27.0 days).

The ARRs significantly declined from 0.10 (95% CI, 0.00-0.22) at baseline to 0.03 (95% CI, 0.00 to 0.08) at 12 months, maintaining stability at 24 months. Median EDSS scores remained consistent, shifting from 2.3 (range, 0.0-5.5) at baseline to 2.0 (range, 0.0-6.0) at 24 months. At study initiation, 97.5% of patients were free from T1 gadolinium-enhancing (Gd+) and new/enlarging T2 lesions, with 100% remaining free from T1 Gd+ lesions and 88.9% free from T2 lesions at 24 months.

Multiple Sclerosis Disease Activity (MSDA) scores were stable or improved at 6-, 9-, 12-, and 24-months post-transition. The most common adverse events included upper respiratory tract infections (12.5%), nausea (10.0%), and headaches (7.5%). During the study period, no instances of progressive multifocal leukoencephalopathy or disease rebound were identified.

“The findings of the 2-year CLADRINA study support continued disease stability after rapidly transitioning from [natalizumab] to [cladribine tablets] and support [cladribine tablets] as an effective and safe option, with no [progressive multifocal leukoencephalopathy] or rebound disease activity, for treatment sequencing of [highly effective] therapies after [natalizumab] therapy,” the researchers concluded.