Similar effects were observed for each proxy SMPS component when compared with placebo.
Gavin Giovannoni, MBBCh, PhD
Regardless of baseline Expanded Disability Status Scale (EDSS) scores, treatment with cladribine tablets was shown to effectively reduce the risks of progressing to secondary progressive multiple sclerosis (SPMS) in patients with relapsing multiple sclerosis (MS) within 2 years of treatment.1
Using results from the post hoc analysis of the CLARITY study, researchers found the overall proxy SPMS progression in just 6.7% of cladribine 3.5 mg/kg patients (n = 433), compared with 13.5% for placebo (odds ratio [OR] 0.46 [95% CI: 0.28, 0.76]; P = .0024). The data were reported at America’s Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) forum, February 27-29, 2020, in West Palm Beach, Florida.
Cladribine, an oral therapy, was approved for the treatment of relapsing MS, as well as progressive MS in March 2019. The treatment showed a significant decrease in the number of relapses experienced by patients who had >1 relapse in the previous year, compared with placebo.2
The CLARITY study, conducted by Gavin Giovannoni, MBBCh, PhD, chair of neurology, Barts and The London School of Medicine and Dentistry, and colleagues, assessed the efficacy of cladribine tablets 10 mg, cumulative dose 3.5 mg/kg in 433 patients against 437 patients in the placebo group. In the post hoc analysis, researchers explored the relationship between baseline EDSS and risk of progression to SPMS or to EDSS >6.0.
Using a proxy composite definition, researchers concluded progression to SPMS was defined as confirmed disability progression (CDP), CDP within the leading EDSS-defined functional system (FS) score, EDSS post-baseline >4.0, pyramidal FS >2. Additionally, these requirements must have been met for at least 3 months in the absence of a relapse. Progression to EDSS >6.0 was defined as having >1 post-baseline EDSS >6.0 with 3- or 6-month CDP.
Treatment and baseline EDSS (<3.0 or >3.5) were used as fixed effects, while odds ratios (ORs) and confidence intervals (Cis) were estimated using a logistic regression model.
Among the 257 in the EDSS <3.0 subgroup administered with cladribine 3.5 mg, proxy SPMS progression occurred in 3.5%, compared to 7.7% of patients administered with placebo (OR, 0.44 [95% CI: 0.19—0.99]; P = .0471). Additionally, similar differences were found in baseline EDSS ≥3.5 subgroup (CT3.5, n = 148; PBO, n = 157), where researchers documented proxy SPMS progression occurred in 12.2% vs 22.4% of CT3.5 vs PBO patients, respectively (OR, 0.48 [95% CI: 0.26—0.9]; P = .0212).
At post-baseline experiences at least 1 >6.0 EDSS value were found in 6.4% and 14.5% of cladribine 3.5 mg/kg and placebo patients, respectively (OR, 0.4 [95% CI, 0.24—0.66]; P = .0004).
Researchers noted that the corresponding proportions for patients with 3-month CDP with EDSS ≥6.0 were 3.5% vs 8.0% (cladribine 3.5 vs placebo; OR, 0.42 [95% CI, 0.22—0.82]; P = .0114). Furthermore, corresponding proportions for patients with 6-month CDP and EDSS >6.0 were 2.8% vs 5.8% (cladribine 3.5 vs placebo; OR 0.48 [95% CI, 0.22—1.02]; P = .0566).
In the subgroup analysis, researchers noted 0.8% of patients who received cladribine 3.5 mg/kg with baseline EDSS <3.0 had at least one EDSS >6.0, compared to 4.3% of patients in placebo (OR, 0.18 [95% CI, 0.04—0.81]; P = .0262).
The corresponding proportions for patients with baseline EDSS >3.5 were 16.2% vs 29.9% in cladribine 3.5 mg/kg and placebo, respectively (OR, 0.45 [95% CI, 0.26—0.79]; P = .0051).
1. Vermersch P, Giovannoni G, Soelberg-Sorensen P, et al. Reduction of risk of secondary progressive multiple sclerosis within 2 years of treatment with cladribine tablets: an analysis of the CLARITY study. Presented at 2020 ACTRIMS forum. February 27-29, 2020; West Palm Beach, Florida. Abstract P113.
2. FDA approves new oral treatment for multiple sclerosis [press release]. Silver Spring, MD: FDA; Published March 29, 2019. Accessed March 3, 2020. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm634837.htm.