Author Of 2 Presentations
P0209 - Efficacy and safety of ofatumumab versus placebo in relapsing multiple sclerosis patients in Japan and Russia: Results from the Phase 2 APOLITOS study (ID 1656)
Abstract
Background
Ofatumumab, a fully human anti-CD20 monoclonal antibody, demonstrated superior efficacy versus teriflunomide with a favorable safety profile in the Phase 3 ASCLEPIOS I/II trials in relapsing multiple sclerosis (RMS) patients (Global, Ex-Japan). APOLITOS was designed to support ofatumumab registration for RMS treatment in Japan in conjunction with ASCLEPIOS.
Objectives
To evaluate the efficacy and safety of ofatumumab versus placebo in RMS patients and assess consistency of effect in Japanese and non-Japanese patients.
Methods
APOLITOS was a 24-week, double-blind, placebo-controlled study followed by an open-label extension up to week 48. Patients aged 18–55 years with confirmed MS diagnosis (2010 revised McDonald criteria), prior evidence of disease activity (≥1 relapse in the last 2 years AND MRI activity in the last year), and an EDSS score of 0–5.5 were randomized (2:1) to subcutaneous ofatumumab 20 mg or matching placebo (initial doses: Days 1, 7, 14, week 4; subsequent doses: every 4 weeks). Randomization was stratified by region (Japan or ex-Japan) and baseline gadolinium-enhancing (Gd+) T1 lesions (0 or ≥1). The primary endpoint was a reduction in cumulative number of Gd+ T1 lesions across weeks 12, 16, 20, and 24. Secondary outcomes included consistency in reduction of Gd+ T1 lesions across regions, annualized relapse rate (ARR), and safety.
Results
In total, 64 patients were randomized (32 each from Japan and Russia; by treatment: ofatumumab, N=43; placebo, N=21), and 59 completed the double-blind phase. The majority of patients had high baseline disease activity ([mean] 1.5 relapses in the last year, 1.2 Gd+ T1 lesions) and 69% received prior disease-modifying therapies. At week 24, ofatumumab significantly reduced Gd+ T1 lesions versus placebo by 93.6% (p<0.001); the results were consistently in favor of ofatumumab across regions. Ofatumumab reduced the ARR versus placebo by 58.0% (p=0.119). Adverse events occurred in 69.8% of patients with ofatumumab and 81.0% with placebo; injection-related reactions were the most common (20.9% and 19.0%, respectively). One ofatumumab-treated patient was diagnosed with serious chronic inflammatory demyelinating polyradiculoneuropathy after completing the study. No deaths, opportunistic infections, or malignancies occurred during the study.
Conclusions
Ofatumumab demonstrated superior efficacy versus placebo in a RMS population with recent disease activity in Japanese and non-Japanese patients. No new safety signals were observed and the results were consistent with the Phase 3 ASCLEPIOS I/II trials.
P0452 - Continued increase of multiple sclerosis and neuromyelitis optica and the north-south gradient in Japan; updates from the 5th nationwide survey (ID 775)
Abstract
Background
In Japan, nationwide survey for multiple sclerosis (MS) including neuromyelitis optica spectrum disorders (NMOSD) has regularly been conducted since 1972, and the past 4 surveys conducted before the discovery of anti-aquaporin 4 antibodies demonstrated the rapid increase of MS.
Objectives
To investigate the epidemiological characteristics of MS and NMOSD in Japan simultaneously through the 5th nationwide survey.
Methods
Preliminary survey was conducted to ascertain the approximate number of patients with either MS (pwMS) or NMOSD (pwNMOSD) who had seen at the selected facilities in 2017. Preliminary survey packages were sent to departments of neurology, internal medicine, ophthalmology, and pediatrics, at the facilities randomly selected using pre-determined sampling rates stratified based on the hospital bed counts. Secondary questionnaire was sent to the facilities with the cases to collect the detailed clinical information of each patient.
Results
Out of 3,799 departments where we sent preliminary survey, 2,284 (60.1%) replied and 645 departments reported the presence of the patients with the diseases. Second questionnaire form was sent to the 645 departments for 13,067 cases, and 6,990 (53.5%) forms were returned for further analysis. Estimated number of pwMS and pwNMOSD were 24,118 in total, which is more than 10-fold higher than that (2,280) of the 1st survey in 1972. The crude prevalence for both MS and NMOSD was 19.6/100,000 (14.3 for MS and 5.3 for NMOSD). Male: female ratios of MS and NMOSD were 1: 2.2 and 1: 4.1, respectively. The onset ages (mean ± standard deviation, year) of MS and NMOSD were 32.3 ± 11.6 and 44.2 ± 16.1, respectively. The Expanded Disability Status Scale scores and disease durations were 2.7 ± 2.4 in 12.9 ± 9.0 years for MS and 3.7 ± 2.4 in 10.9 ± 9.5 years for NMOSD. Disease-modifying therapy had been used for 77.2% in MS. The proportion of pwNMOSD against pwMS was 1: 0.37. Based on the prefectures at birth, the distribution of pwMS demonstrated north-south gradient (ρ = 0.39, p = 0.008), although no significant gradient was observed in pwNMOSD. Based on the registered sites, the proportion of pwMS among both pwMS and pwNMOSD showed north-south gradient (ρ = 0.4, p = 0.004).
Conclusions
As the combined prevalence of MS and NMOSD was 7.7/100,000 in the 4th survey (4.4 for conventional MS and 3.3 for others including opticospinal form), the prevalence of both MS and NMOSD appears to be still increasing. Disease severity may have become milder in MS and NMOSD compared with the 4th survey (3.5 ± 2.9 in conventional MS and 4.3 ± 2.7 in opticospinal form), though the disease durations in the two studies were comparable. Higher latitude is a risk for MS but not NMOSD in Japanese.