Cladribine is associated with stable or improved cognition over 4 years in RMS

A pooled analysis of data from the extension of the CLARIFY-MS and MAGNIFY-MS studies assessed the long-term effects of cladribine on cognitive function in patients with relapsing MS (RMS). Results showed that most participants had stable or improved cognitive function, with clinically meaningful improvements or stability in cognitive processing speed (CPS) observed over 4 years [1].

Cognitive decline is a highly prevalent and debilitating symptom of MS, often present even at early stages of the disease. The CLARIFY-MS (NCT03369665) and MAGNIFY-MS (NCT03364036) studies showed that short-course cladribine tablets can stabilise or improve cognitive function for up to 4 years, as measured by the Symbol Digit Modalities Test (SDMT) [2,3]. The pooled analysis included data from 499 patients: 280 participating in the CLARIFY-MS extension (NCT00641537) and 219 in the MAGNIFY-MS extension (NCT04783935). All participants received short-course cladribine (cumulative dose of 3.5 mg/kg) in years 1 and 2, followed by a treatment-free period in years 3 and 4.

At baseline, the mean age was 37.9 years, 68.7% were women, and the median SDMT was 53 points. After 48 months, the least-squares mean SDMT scores improved by 1.79 points (95% CI 1.05–2.54; P<0.0001) in the total population and by 2.22 points (95% CI 1.40–3.04; P<0.0001) in patients aged <50 years (n=434). SDMT in patients aged ≥50 years (n=65) improved by 0.81 points (95% CI -4.97 to 6.59; P=0.7806), which was not statistically significant.

Most participants had stable or improved SDMT scores after 48 months. Using a threshold of a ≥4-point change, 74.4% were stable or improved, and 25.2% worsened. A ≥8-point change threshold yielded proportions of 86.6% and 12.9%, respectively. Percentages of stable or improved patients were relatively high among patients aged ≥50 years and among those with low (<53) versus high (≥53) baseline SDMT scores.

Based on these findings, the authors suggested that cladribine tablets have long-term benefits beyond their effects on conventional disability measures, particularly when initiated at an early stage of MS. This complementary effect, the authors noted, supports early use to maximise benefit.

Brochet B, et al. Cladribine tablets maintain or improve cognition over 4 years in people with relapsing multiple sclerosis: Pooled analyses of the CLARIFY-MS and MAGNIFY-MS Extension Studies. P117, ACTRIMS Congress 2026, 4–7 February, San Diego, California, USA.
Selmaj K, et al. Sustained disease-activity-free (NEDA) status in patients with relapsing multiple sclerosis (RMS) treated with cladribine tablets: data from the CLARITY extension study. P846, ECTRIMS Congress 2024, 18–20 September, Copenhagen, Denmark.
De Stefano N, et al. Long-term effectiveness of cladribine tablets over 4 years in relapsing multiple sclerosis: Results from the MAGNIFY-MS Extension study. P349, ECTRIMS Congress 2024, 18–20 September, Copenhagen, Denmark.