Satralizumab monotherapy may reduce the risk for neuromyelitis optics spectrum disorder (NMOSD) relapse and has a favorable safety profile, according to study results published in Lancet Neurology.
Satralizumab is a humanized monoclonal antibody that targets the interleukin-6 receptor. In the SAkuraSky study (ClinicalTrials.gov Identifier: NCT02028884), adding satralizumab to baseline immunosuppressant reduced the risk for relapse in NMOSD. The goal of the current phase 3 randomized trial (SAkuraStar; ClinicalTrials.gov Identifier: NCT02073279) was to investigate the safety and efficacy of satralizumab monotherapy, compared to placebo, in adults with NMOSD.
The study included adults aged 18-74 years with aquaporin-4 antibody seropositive or seronegative NMOSD at 44 sites in 13 countries. All participants had ≥1 documented NMOSD attack or relapse within the past 12 months and had a score of up to 6.5 on the Expanded Disability Status Scale.
The participants were randomly assigned 2:1 to receive satralizumab 120 mg or placebo, with subcutaneous injection given at weeks 0, 2, 4 and every 4 weeks thereafter. The primary outcome was time to first relapse and the researchers also assessed the safety in all participants who received ≥1 dose of satralizumab or placebo.
Following a double-blind phase, the participants could enter an open-label phase but only after a protocol-defined relapse that was confirmed by the Clinical Endpoint Committee.
The study included 95 patients, of which 63 received satralizumab and 32 received placebo. In total, protocol-defined relapses occurred in 19 patients (30%) receiving satralizumab, compared to 16 (50%) patients receiving placebo (hazard ratio [HR] 0.45, 95% CI, 0.23 to 0.89, P =.018).
Patients treated with placebo showed a shorter time to relapse and a higher withdrawal rate than did patients treated with satralizumab.
In the aquaporin-4 seropositive subgroup, 9 (22%) of 41 patients receiving satralizumab compared to 13 (57%) of 23 receiving placebo experienced a relapse (HR 0.26, 95% CI, 0.11-0.63). In the aquaporin-4 seronegative subgroup, 10 (46%) of 22 patients receiving satralizumab compared to 3 (33%) of 9 receiving placebo experienced a relapse (HR 1.19, 95% CI, 0.30-4.78).
The rate of adverse events in the satralizumab cohort was 473.9 events per 100 patient-years compared to 495.2 events per 100 patient-years in the placebo group. The incidence of serious adverse events (19% vs 12%, respectively) and adverse events leading to withdrawal was similar between groups. The most commonly reported adverse events were urinary tract infection and upper respiratory tract infection.
The researchers acknowledged several study limitations, including the relatively small group sizes and low number of relapses.
“Based on these positive results, satralizumab has the potential to become a valuable treatment option for patients with NMOSD,” concluded the researchers.
Disclosure: This clinical trial was supported by Chugai Pharmaceutical (Roche). Please see the original reference for a full list of authors’ disclosures.
Traboulsee A, Greenberg BM, Bennett JL, et al. Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial. Lancet Neurol. 2020;19(5):402‐412. doi:10.1016/S1474-4422(20)30078-8