Two short courses of oral cladribine (Mavenclad®, Merck KGaA) over a period of two years can sustain the No Evidence of Disease Activity-3 (NEDA-3) status in certain relapsing-remitting multiple sclerosis (RRMS) patients for up to three additional years without further treatment, a new analysis presented at the 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2018 suggests.¹Giovannoni G, et al. 34th Congress of ECTRIMS; 2018 Oct 10-12; Berlin (Germany). Poster P894.

CLARITY

The CLARITY study was a 2-year, Phase III, randomised controlled trial that had demonstrated significant efficacy with oral cladribine vs placebo. After the completion of CLARITY, patients in the two dosing arms of oral cladribine were re-randomised to cladribine or placebo in the CLARITY Extension study.

Of the 284 CLARITY-patients who received a cumulative dose oral cladribine of 3.5 mg/kg over 2 years, 98 were re-randomised to placebo and 186 were re-randomised to continue cladribine at the initial dosing in CLARITY Extension. The durability of the NEDA-3 status was assessed by investigators in the first year of CLARITY Extension.

NEDA-3 was defined as the absence of relapses, no 6-month Expanded Disability Status Scale (EDSS) progression and no T1 gadolinium-enhancing (Gd+) or active T2 lesions on MRI.

The bridging interval between the CLARITY and CLARITY Extension participants varied; some participants had an interval <43 weeks between CLARITY and CLARITY Extension (Year 3 – 4 group), whereas others had an interval >43 weeks between the two studies (Year 4 – 5 group).

In the Year 3 – 4 group, annual NEDA-3 was achieved in 46.3% of patients who were randomised to cladribine in CLARITY followed by placebo in the CLARITY Extension, vs 48.0% of whom were received cladribine in both studies. In the Year 4 – 5 group, annual NEDA-3 was achieved in 35.0% of patients receiving cladribine followed by placebo and 48.1% of patients receiving cladribine in both protocols, respectively.

After adjustment for length of bridging interval, the rate of annual NEDA-3 was 41.5% in patients receiving cladribine in CLARITY and placebo in the CLARITY Extension vs 48.0% in patients receiving cladribine in both studies (odds ratio=1.3; 95% CI, 0.8-2.2; P=0.31).

The constituent elements of NEDA-3 were further analysed to explain the numerically lower rate in the Year 4 – 5 group. Only the rates of freedom from T1 Gd+ MRI (73.0% vs 92.2%) and active T2 MRI (41.0% vs 52.0%) lesions were generally lower in patients without further cladribine treatment; the proportions of patients with freedom from relapse or from 6-month EDSS progression were “largely similar”.

The investigators concluded that for both groups of patients receiving placebo or cladribine after a 2-year course of oral cladribine 3.5 mg/kg, they “experienced sustained benefits for NEDA-3, or its components” in the CLARITY Extension.