TOPLINE:

Cladribine was associated with similar relapse rates and MRI activity as sphingosine-1-phosphate receptor modulators (S1PRMs) in treatment-naive patients with relapsing-remitting multiple sclerosis (RRMS), a new study showed. Although it was associated with a 36% lower risk for progression of disability than S1PRMs over 25 months, risk for relapse was increased after 3 years.

METHODOLOGY:

• Researchers conducted a real-world comparative effectiveness study across 108 Italian MS centers, analyzing data for 950 propensity score-matched treatment-naive patients (mean age, 35 years; 72% women) with RRMS.
• Half of the patients started cladribine and half started S1PRMs (fingolimod, ozanimod, or ponesimod) as their first disease-modifying therapy between 2011 and 2021. The median follow-up duration was 25 months.
• Primary outcomes included rates of relapse (new neurologic symptoms lasting more than 24 hours), disability worsening (increases of 1.5, 1.0, or 0.5 score points on the Expanded Disability Status Scale [EDSS]), MRI activity (new and/or enlarged lesions on T2-weighted images), and the proportion who achieved no evidence of disease activity (NEDA-3) status.
• Secondary outcomes included progression independent of relapse activity (PIRA), relapse-associated worsening, and treatment discontinuation.

TAKEAWAY:

• Relapse rates, MRI activity, and loss of NEDA-3 status were not significantly different between the cladribine and S1PRM groups.
• Cladribine was associated with a lower risk for disability worsening than S1PRM (hazard ratio [HR], 0.64; P = .03), particularly in patients younger than 40 years (HR, 0.5; P = .03) and primarily driven by fewer PIRA events (HR, 0.40; P = .009). No significant difference was found in relapse-associated worsening events between groups.
• In sensitivity analyses, the protective effect of cladribine against the progression of disability remained significant in patients with a baseline EDSS score ≤ 3.0 (HR, 0.62; P = .04) and those diagnosed using 2017 McDonald criteria (HR, 0.48; P = .03).
• Beyond 36 months, use of cladribine was associated with a higher risk for relapse (HR, 1.81; P = .04) and increased loss of NEDA-3 status (HR, 2.08; P = .01). Discontinuation rates were similar between the treatment groups (HR, 0.92).

IN PRACTICE:

“These findings suggest cladribine may provide greater short-term protection against disability progression, with a possible need for redosing or treatment switch to sustain disease control beyond 3 years,” the investigators wrote. 

SOURCE:

The study was led by Shalom Haggiag, MD, Azienda Ospedaliera San Camillo-Forlanini, Rome, Italy. It was published online on November 3 in JAMA Network Open.

LIMITATIONS:

The study’s observational, nonrandomized design may have introduced confounding. The 25-month follow-up period may not have captured long-term effects. Selection bias was possible as a large proportion of patients treated with S1PRMs was excluded during matching. Treatment adherence and tolerability were not assessed, and inconsistencies in timing and frequency of visits and MRI scans may have affected the accuracy. No prespecified primary outcome was set, nor was an adjustment for multiple comparisons made, and grouping the three S1PRMs assumed similar effectiveness.

DISCLOSURES:

The study was funded by the Fondazione Italiana Sclerosi Multipla. Several investigators reported having financial or other ties with various pharmaceutical companies. Full details are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.