Abstract| Volume 37, 101602, January 2020

Reduction of Risk of Secondary Progressive Multiple Sclerosis Within Two Years of Treatment with Cladribine Tablets: An Analysis of the CLARITY Study

      Cladribine tablets 10mg (cumulative dose 3.5mg/kg [CT3.5];N=433) over 2 years showed efficacy vs placebo (PBO;N=437) in patients with relapsing multiple sclerosis (CLARITY). This post hoc analysis explored the relationship between baseline expanded disability status scale (EDSS) and risk of progression to secondary progressive multiple sclerosis (SPMS) or to EDSS ≥6.0, in CLARITY.
      Progression to SPMS was not recorded during the trial, a proxy composite definition was used: confirmed disability progression (CDP), CDP within the leading functional score (FS), EDSS post-baseline ≥4.0, pyramidal FS ≥2, all conditions met for ≥3 months in the absence of a relapse. Progression to EDSS≥6.0 was defined by having ≥1 post-baseline EDSS≥6.0 with 3- or 6-month CDP. Odds ratios (OR) and corresponding confidence intervals (CI) were estimated by a logistic regression model with treatment and baseline EDSS (≤3.0 or ≥3.5) as fixed effects.
      Proxy SPMS progression occurred in 6.7% CT3.5 patients vs 13.5% PBO (OR 0.46[95%CI:0.28,0.76]; p=0.0024). For baseline EDSS≤3.0 patients, proxy SPMS progression was 3.5%(CT3.5,n=257) vs 7.7%(PBO,n=235); OR 0.44(95%CI:0.19,0.99); p=0.0471. Baseline EDSS≥3.5, proxy SPMS progression was 12.2%(CT3.5,n=148) vs 22.4%(PBO,n=157); OR 0.48(95%CI:0.26,0.9); p=0.0212. Proportions of patients with ≥1 EDSS value ≥6.0 post-baseline were 6.4%(CT3.5) vs 14.5%(PBO); OR 0.4(95%CI:0.24,0.66); p=0.0004. Patients with 3-month CDP with EDSS≥6.0 were 3.5%(CT3.5) vs 8.0%(PBO); OR 0.42(95%CI:0.22,0.82); p=0.0114, patients with 6-month CDP with EDSS≥6.0, were 2.8%(CT3.5) vs 5.8%(PBO); OR 0.48(95%CI:0.22,1.02); p=0.0566. Patients with baseline EDSS≤3.0 that had ≥1 EDSS≥6.0, 0.8%(CT3.5) vs 4.3%(PBO); OR 0.18(95%CI:0.04,0.81); p=0.0262. Baseline EDSS≥3.5, 16.2%(CT3.5) vs 29.9%(PBO); OR 0.45(95%CI:0.26,0.79); p=0.0051.
      The risks of progressing to SPMS (proxy) within 2 years of treatment, or experiencing EDSS≥6.0, were significantly reduced with CT3.5 vs PBO, regardless of baseline EDSS (≤3.0 or ≥3.5).