Two trials comparing relapsing MS treatments

Ofatumumab markedly reduced disability progression independent of relapses versus teriflunomide [1]. In another head-to-head trial, ponesimod was superior to teriflunomide with regard to annualised relapse rate (ARR), fatigue symptoms, MRI activity, brain atrophy, and no evidence of disease activity (NEDA) in the OPTIMUM study [2,3].

In a pooled analysis of the phase 3 ASCLEPIOS I/II trials in relapsing multiple sclerosis (RMS) patients, the effect of ofatumumab versus teriflunomide on confirmed disability progression independent of relapse activity (PIRA) was assessed. The risk of confirmed disability progression at 3/6 months (3mCDP/6mCDP) was evaluated in 3 subsets of patients:

A: without confirmed relapses during the study;

B: without confirmed relapses during the study or prior to a 3mCDP/6mCDP event;

C: with secondary progressive MS diagnosis at study entry and without confirmed relapses during the study.

In all subsets, ofatumumab significantly reduced the risk of 3mCDP and 6mCDP versus teriflunomide, except for 6mCDP in the small Subset-C (see Table). An inverse probability censoring weighted estimation of PIRA confirmed a significant risk reduction for ofatumumab versus teriflunomide of 46.0% for 3mCDP (HR 0.540; 95% CI 0.396-0.738; P<0.001) and 42.5% for 6mCDP (HR 0.575; 95% CI 0.409-0.808; P=0.001).

Table. Risk of 3mCDP and 6mCDP with ofatumumab versus teriflunomide [1].



n, number of patients with the specified event; N, total number of patients included in the analysis; 3mCDP, confirmed disability progression at 3 months; 6mCDP, confirmed disability progression at 6 months

In the superiority phase 3 OPTIMUM trial, the efficacy and safety of ponesimod and teriflunomide were compared [2,3] in 1,133 adult RMS patients (18-55 years) with an expanded disability status scale (EDSS) score of 0-5.5. They were randomised to ponesimod 20 mg or teriflunomide 14 mg once daily for 108 weeks.

The ARR for ponesimod and teriflunomide was 0.202 and 0.290, corresponding to a relative rate reduction (RRR) with ponesimod of 30.5% (P=0.0003). Respective mean change from baseline in fatigue symptom and impact questionnaire-RMS weekly symptoms score was 0.01 versus 3.57 (P=0.0019). Mean number of combined unique active lesions per year (CUALs) on MRI was 1.405 versus 3.164 (RRR 56%, P<0.0001). Time to 12- and 24-week confirmed disability accumulation risk estimates were reduced by 17% (P=0.29) and 16% (P=0.37), respectively.

In general, the safety of ponesimod and teriflunomide was comparable after 108 weeks [2]. Incidence of treatment-emergent adverse events (TEAEs) (88.8% vs 88.2%) and serious AEs (8.7% vs 8.1%) were similar. TEAEs leading to treatment discontinuation were 8.7% and 6.0%. Most common TEAEs were increased alanine aminotransferase levels (19.5% vs 9.4%), nasopharyngitis (19.3% vs 16.8%), headache (11.5% vs 12.7%), and upper respiratory tract infection (10.6% vs 10.4%).

 

1. Kappos L, et al. Abstract O2034, EAN 2020.


2. Kappos L, et al. Abstract S40.010, AAN 2020.


3. Sprenger T, et al. Abstract P5.021, AAN 2020.

 





Posted on 10 September, 202022 February, 2021