Data from the CLARITY extension trial suggest that the durability of treatment with cladribine extended beyond 24 months in those with relapsing-remitting multiple sclerosis.
Gavin Giovannoni, MBBCh, PhD
The durability of treatment with cladribine (Mavenclad, EMD Serono) has been shown to extend beyond 2 years in patients with relapsing-remitting multiple sclerosis (MS) who were treated with 3.5 mg/kg tablets in the CLARITY study.1
The data, presented at the 2020 America’s Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, February 27-29, 2020, in West Palm Beach, Florida, showed that those who switched to placebo (n = 98) in the CLARITY extension had comparable relapse-free status over time compared to those who continued on therapy (n = 186). Those who switched to placebo had an annualized relapse rate (ARR) of 0.15 (97.5% CI, 0.09—0.21), while those who continued treatment had an ARR of 0.10 (97.5% CI, 0.06­–0.13).
Lead investigator in the CLARITY studies Gavin Giovannoni, MBBCh, PhD, chair of neurology, Barts and The London School of Medicine and Dentistry, and colleagues randomized those who were treated with cladribine 3.5 mg/kg in CLARITY, which were years 1 and 2 of the study, who then continued to years 3 and 4 in the extension. The data included all qualifying relapses for the patients from the start of CLARITY to the end of the extension—including the average 41-week gap between studies.
In the CLARITY study, those with relapsing-remitting MS who were treated with cladribine showed significant reductions in ARR (0.14; 95% CI, 0.12—0.17) compared to placebo (0.33; 95% CI, 0.29–0.38) over the 2 years. This, Giovannoni and colleagues wrote, represents a 58% relative reduction in the ARR with cladribine (P <.001).
All told, the proportions of patients in the cladribine-placebo switch group who were relapse-free were relatively similar to the continued treatment group. In Year 1, those proportions were 85.7% (95% CI, 77.1—91.3) and 90.9% (95% CI, 85.7–94.2), respectively, followed by 83.7% (95% CI, 74.7–89.7) and 82.8% (95% CI, 76.6-87.5) in Year 2.
In years 3 and 4, those proportions for the cladribine-to-placebo group were 74.4% (95% CI, 64.5—81.9), and 70.2% (95% CI, 60.0–78.2) in Year 4. For comparison, the proportions of relapse-free patients in the cladribine-to-cladribine group at these time points were 76.3% (95% CI, 69.5–81.8), and 72.4% (95% CI, 65.4–78.3).
Cladribine was approved as an oral therapy for the treatment of relapsing multiple sclerosis (MS), as well as active secondary progressive MS in March 2019, though it is not recommended for use among patients with clinically isolated syndrome.2
The purine analog is a synthetic agent that targets lymphocytes and selectively suppresses the immune system, with the goal of depleting lymphocytes in order to “reset” it. It was approved based on the data from a trial including more than 1300 patients with relapsing forms of MS, ultimately showing a significant decrease in the number of relapses experienced by patients who had ≥1 relapse in the previous year, compared to placebo.
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1. Giovannoni G, Pardo G, Ben-Zacharia A, et al. Time To First Relapse Over The Duration Of Clarity And Clarity Extension In Patients Treated With Cladribine Tablets 3.5 Mg/kg Over Two Years. Presented at 2020 ACTRIMS Forum. February 27-29, 2020; West Palm Beach, FL. Abstract P074.
2. FDA approves new oral treatment for multiple sclerosis [press release]. Silver Spring, MD: FDA; Published March 29, 2019. Accessed February 27, 2020. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm634837.htm.