Cladribine Tied to Lower Relapse Rates, Higher Treatment Persistence in MS

Compared with fingolimod, dimethyl fumarate (DMF), and teriflunomide, the use of cladribine tablets for the treatment of relapsing multiple sclerosis (MS) is associated with lower relapse rates and higher treatment persistence, 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.

The real-world study, conducted using data from the MSBase registry, analyzed treatment outcomes in adult patients who initiated cladribine or 1 of the 3 oral disease-modifying therapies (fingolimod, DMF, and teriflunomide), from January 2018 onward.

Researchers applied propensity score matching (1:1) to create balanced comparison groups, adjusting for variables such as age, sex, disease duration, baseline disability scores, pre-baseline relapses, prior treatment history, and country of treatment. Key outcomes included annualized relapse rate (ARR), time to first relapse, and time to treatment discontinuation.

For the study, the researchers analyzed over 6000 matched patients, with median follow-up periods ranging from 15 to 23 months:

• cladribine vs fingolimod: 1965 matched pairs
• cladribine vs DMF: 2064 matched pairs
• cladribine vs teriflunomide: 2069 matched pairs

Across all comparisons, cladribine was associated with significantly lower relapse rates and higher treatment persistence.

In the cladribine vs fingolimod group (n=1965 per arm), the ARR was 0.11 vs 0.13 (P =.0013). Patients treated with cladribine had a 19% lower risk for first relapse (hazard ratio [HR], 0.81; 95% CI, 0.70-0.93; P =.004) and a 69% reduction in treatment discontinuation risk (HR, 0.31; 95% CI, 0.27-0.36; P <.001).

Compared with DMF (n=2064 per arm), cladribine showed an ARR of 0.10 vs 0.13 (P <.001), with a 31% lower risk for first relapse (HR, 0.69; 95% CI, 0.59-0.80; P <.001) and an 83% reduction in discontinuation risk (HR, 0.17; 95% CI, 0.15-0.19; P <.001).

In the cladribine vs teriflunomide group (n=2069 per arm), ARR was 0.09 vs 0.14 (P <.001). Cladribine treatment was associated with a 41% lower risk for first relapse (HR, 0.59; 95% CI, 0.51-0.68; P <.001) and a 78% lower likelihood of discontinuation (HR, 0.22; 95% CI, 0.19-0.25; P <.001).

Subgroup analyses in patients with relapsing-remitting MS or clinically isolated syndrome at baseline confirmed the advantage of cladribine. Compared with fingolimod, cladribine resulted in an 18% reduction in first relapse risk (HR, 0.82; P =.008) and a 69% reduction in discontinuation risk (HR, 0.31; P <.001).

Against DMF, cladribine reduced first relapse risk by 31% (HR, 0.69; P <.001) and discontinuation by 83% (HR, 0.17; P <.001). Compared with teriflunomide, cladribine reduced first relapse risk by 42% (HR, 0.58; P <.001) and discontinuation by 78% (HR, 0.22; P <.001).

“For all three pairwise comparisons, relapse and discontinuation outcomes significantly favored [cladribine tablets]. Future analyses with longer follow-up comparing disability progression events are warranted,” the researchers concluded.