New data confirm cladribine’s efficacy as a treatment for relapsing-remitting multiple sclerosis (MS), according to results published online ahead of print August 1 in Multiple Sclerosis Journal. The drug’s effect on relapses is comparable to that of fingolimod, and its effect on disability accumulation is comparable to those of interferon β and fingolimod. Compared with interferon, fingolimod, and natalizumab, cladribine may be associated with superior recovery from disability.
A phase III trial demonstrated that, compared with placebo, cladribine reduced relapse rate and increased the likelihood of remaining free from three-month confirmed disability progression in patients with relapsing-remitting MS. The European Medicines Agency approved the therapy in August 2017. Cladribine’s potential position in the treatment landscape is unclear, however, because no direct comparisons of cladribine with other MS therapies are available.
An Analysis of Matched Cohorts
Tomas Kalincik, MD, PhD, Professor of Medicine at Royal Melbourne Hospital in Australia, and colleagues conducted a propensity score–matched analysis of observational data from MSBase, including patients from the Australian Cladribine Product Familiarization Program, to compare the effectiveness of cladribine to that of interferon β, fingolimod, and natalizumab. Eligible participants had relapsing-remitting MS, received one of the study medications as monotherapy for one or more years, and had no prior exposure to alemtuzumab, mitoxantrone, rituximab, or hematopoietic stem cell transplantation.
Patients received 3.5 mg/kg of oral cladribine, 44 μg of subcutaneous interferon β-1a three times weekly, 0.5 mg/day of oral fingolimod, or 300 μg of IV natalizumab every four weeks. Data were recorded during routine clinical practice. The primary end points were the proportion of patients free from relapses, disability accumulation, and disability improvement while on study therapy.
Cladribine Was Associated With Superior Disability Improvement
The researchers included 37 patients treated with cladribine, 1,940 patients treated with interferon β, 1,892 patients treated with fingolimod, and 1,410 patients treated with natalizumab in their analysis. The investigators noted only small differences in baseline characteristics between the matched cohorts.
Compared with participants receiving interferon β, patients receiving cladribine were less likely to have a relapse during the first year of treatment (hazard ratio [HR], 0.6). The proportion of relapse-free patients was 86% in the cladribine group and 70% in the interferon β group. The probability of disability accumulation was similar for these drugs (HR, 0.41), but the cladribine group was more likely to have disability improvement (HR, 15).
The proportion of relapse-free patients at one year was 79% in the cladribine and fingolimod groups, and cumulative hazards of a relapse did not differ between the two groups (HR, 1.2). The probability of disability accumulation was similar for cladribine and fingolimod (HR, 1.8), but the probability of disability improvement was greater for cladribine (HR, 3.9).
The probability of relapse was higher with cladribine than with natalizumab (HR, 1.8), but the proportions of relapse-free patients at the end of year one were 80% and 81%, respectively. The probability of disability accumulation was greater in the cladribine group than in the natalizumab group (HR, 2.5). The probability of disability improvement was greater among patients receiving cladribine than among those receiving natalizumab (HR, 4). Sensitivity analyses largely confirmed the results of the primary analyses.
“Six-month confirmed improvement of disability was observed in 10%–20% of the cladribine cohort during the first year, which was superior to all three comparator therapies. This [finding] is of interest in the context of the comparison to natalizumab, which is known to be associated with a marked improvement in disability early after its commencement,” said Dr. Kalincik and colleagues. “Improvement in disability in a cohort with this profile is unexpected.”
The study’s main limitation is the small size of the cladribine cohort, said the authors. Another limitation is the brief duration of follow-up for the cladribine group, which precludes conclusions about long-term outcomes. Nevertheless, the comparative effectiveness results “represent timely information about the role of cladribine in the management of MS,” Dr. Kalincik concluded.
—Erik Greb
Suggested Reading
Kalincik T, Jokubaitis V, Spelman T, et al. Cladribine versus fingolimod, natalizumab and interferon β for multiple sclerosis. Mult Scler. 2017 Aug 1 [Epub ahead of print].
