Cladribine shows durable efficacy for reducing frequency and severity of relapses in patients with relapsing-remitting multiple sclerosis, according to study results published in Multiple Sclerosis Journal.
Treatment with cladribine tablets 3.5 mg/kg in patients with relapsing-remitting multiple sclerosis significantly reduced the annualized relapse rate compared with placebo in the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) trial (Clinicaltrials.gov Identifier: NCT00213135), an effect that was sustained in CLARITY Extension trial (Clinicaltrials.gov Identifier: NCT00641537) without further treatment.
The objective of the post hoc analysis was to determine the frequency and severity of relapses in patients treated with cladribine, compared with placebo, in the CLARITY trial and to assess the durable effect, without further treatment, in patients who received placebo in the CLARITY Extension trial after treatment with cladribine in CLARITY.
Qualifying relapses were defined as 2 point increase in at least 1 Kurtzke Functional Systems score or 1 point increase at least 2 Kurtzke Functional Systems scores. All relapses included both qualifying relapses and nonqualifying relapses. Severe relapses were defined as relapses that required steroid treatment or hospitalization.
The current post hoc analysis included data on 433 patients treated with cladribine 3.5 mg/kg and 437 patients given placebo in the CLARITY trial and data on 98 patients from the cladribine treatment group given placebo in the CLARITY Extension trial.
In the CLARITY trial, the risk for qualifying or all relapses and the risk for severe relapse were significantly lower in patients treated with cladribine 3.5 mg/kg compared with placebo at Month 6, end of Year 1, and the end of Year 2. Compared with placebo, treatment with cladribine tablets reduced annualized relapse rates for both relapses requiring steroid treatment or leading to hospitalization by over 50% compared with placebo.
The reduction in annualized relapse rates for both qualifying and all relapses in the cladribine group at Year 2 in CLARITY was sustained in the patients treated initially with cladribine for 2 years followed by placebo in CLARITY Extension. Concerning qualifying and all relapses, 84.7% and 73.5% of patients, respectively, had no relapses at year 4 in CLARITY Extension. These findings suggest that the treatment effect of cladribine tablets 3.5 mg/kg can be sustained without further treatment after 2 years.
The durability of the effect of cladribine was also supported by lower relapse frequencies for patients from the cladribine treatment group who received placebo in the CLARITY Extension study, compared with those who received placebo in CLARITY.
The general safety profile of patients in the placebo or cladribine tablets 3.5 mg/kg group in CLARITY and the CLARITY Extension was similar.
This study was limited by the reduction in number of patients entering the CLARITY Extension trial from the preceding CLARITY trial. Additionally, some patients who entered CLARITY Extension may have had milder disease.
“[P]atients who received cladribine tablets 3.5 mg/kg had a significant reduction in the frequency and severity of relapses during CLARITY. Additional descriptive analyses suggested that this benefit was sustained in CLARITY Extension without further treatment,” concluded the study researchers.
Disclosure: This research was supported by Merck KGaA, Darmstadt, Germany. Please see the original reference for a full list of disclosures.
De Stefano N, Sormani MP, Giovannoni G, et al. Analysis of frequency and severity of relapses in multiple sclerosis patients treated with cladribine tablets or placebo: The CLARITY and CLARITY Extension studies. Mult Scler. Published online May 10, 2021. doi:10.1177/13524585211010294