Cladribine Noninferior to Fingolimod in Relapsing Multiple Sclerosis

Cladribine is noninferior to fingolimod in the treatment of patients with highly active relapsing multiple sclerosis (HA-RMS), according to study findings published in the journal Multiple Sclerosis and Related Disorders.

A common treatment for relapsing-remitting multiple sclerosis (RRMS) is disease-modifying therapy (DMT). The only oral DMTs approved by the European Union for RRMS are fingolimod and cladribine and there were no head-to-head studies conducted on these medications previously. For the study, researchers assessed the relapse rates among patients with HA-RMS who received either cladribine tablets or fingolimod. 

The researchers conducted a multicenter, retrospective study, MavEnclad Real worLd comparative efficacY non-iNterventional (MERLYN), that focused on patients with HA-RMS in the United Kingdom and Germany.  

The primary outcome was the annualized relapse rate (ARR) and secondary outcomes were the differences between relapse outcomes, disability scores, and radiological disease activity between these 2 treatments. The induction period was defined as the first 12 weeks of treatment and the effectiveness period was the 9 months following. 

The researchers identified a total of 1,098 patients who met the inclusion criteria from 36 sites. After exclusion, 1,095 patients who completed at least 12 weeks of treatment remained in the analysis, with 610 (55.7%) receiving cladribine tablets and 485 (44.3%) receiving fingolimod. The average age at baseline was 39.9 years (standard deviation [SD], 11.3 years), 70% of participants were women, and 88.7% of participants were White. 

Among this study population, 457 (41.7%) patients had received a prior DMT and 187 (17.1%) patients experienced 2 or more relapses prior to starting their current treatments.

Disability was assessed using the Expanded Disability Status Scale (EDSS), with scores ranging from 0 to 10. The median baseline EDSS score was 2.5 (range, 0-8.5).

Of the patients who were treated with cladribine, 42 (6.9%) patients relapsed in the effectiveness period of the study. The adjusted ARR for cladribine tablets was 0.10 (95% CI, 0.07-0.14) and 0.14 (95% CI, 0.10-0.20) for fingolimod. The adjusted ARR ratio was 0.68 (95% CI, 0.42-1.11).

A sensitivity analysis conducted with all patients meeting the study criteria revealed that 65 (10.7%) of patients on cladribine relapsed compared to 51 (10.5%) patients who received fingolimod. The adjusted ARR for the sensitivity analysis for cladribine tablets was 0.11 (95% CI, 0.09-0.15) and 0.13 (95% CI, 0.10-0.18) for fingolimod. The adjusted ARR ratio was 0.84 (95% CI, 0.57-1.26).

“[D]espite having had more relapses prior to baseline, the clinical outcomes of the cladribine tablets group had a more positive trend compared with the fingolimod group after completing the induction period, suggesting that cladribine tablets may provide better control of HA-RMS,” the researchers wrote.

Study limitations include missing data, unmeasured confounding variables, and lack of safety data. 

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.