A NEW comparative study has found that cladribine provides greater protection against disability progression than sphingosine-1-phosphate receptor modulators in Treatment-Naive Relapsing-Remitting MS, while maintaining comparable relapse rates and MRI outcomes over a two-year period.
Comparative Evidence in Treatment-Naive Relapsing-Remitting MS
Early treatment choice is critical in multiple sclerosis care, especially for newly diagnosed patients. This study examined the real-world effectiveness of cladribine compared with S1P receptor modulators (S1PRMs) in Treatment-Naive Relapsing-Remitting MS.
The study, involving patients treated between January 2011 and October 2021, aimed to assess how each therapy affected disease activity and disability progression in those with no prior disease-modifying therapy. Data were drawn from 108 Italian MS centres affiliated with the Italian Multiple Sclerosis and Related Disorders Register, providing one of the most comprehensive analyses to date.
Comparative Methods and Clinical Findings
Among 1,587 participants, 475 pairs of patients were propensity-matched for baseline characteristics and follow-up duration, yielding 950 individuals (mean age 34.7 years; 72.2% female). Over a median follow-up of 25 months, relapse rates were similar between cladribine and S1PRM users (15.2% vs 16.0%), as were MRI activity and NEDA-3 loss (44.4% vs 52.2%). However, cladribine showed a lower risk of confirmed disability worsening (11.4% vs 14.7%; HR 0.64, 95% CI 0.42–0.96; P = .03). This effect appeared to stem from reduced progression independent of relapse activity (HR 0.40, 95% CI 0.20–0.79; P = .009).
After 36 months, cladribine-treated patients displayed an increased relapse risk (HR 1.81, 95% CI 1.02–3.20; P = .04) and greater NEDA-3 loss (HR 2.08, 95% CI 1.18–3.67; P = .01), suggesting the need for re-evaluation of dosing schedules in long-term management of Treatment-Naive Relapsing-Remitting MS.
Clinical Implications and Future Directions
For clinicians, these findings highlight the potential of cladribine as a first-line option for delaying disability progression in Treatment-Naive Relapsing-Remitting MS, particularly in younger patients and those with lower baseline disability. However, sustained disease control beyond three years may require redosing or treatment switching. The authors recommend further prospective studies to validate these findings, assess quality-of-life outcomes, and refine long-term treatment strategies for people living with multiple sclerosis.
Reference
Haggiag S et al. Comparative effectiveness of cladribine and s1p receptor modulators in treatment-naive relapsing-remitting MS. JAMA Netw Open. 2025;8(11):e2541025.
