Author Of 1 Presentation
FC01.02 - Efficacy and safety of eculizumab in patients with neuromyelitis optica spectrum disorder previously treated with rituximab: findings from PREVENT
Abstract
Background
In PREVENT, eculizumab was associated with a significant reduction in relapse risk versus placebo and was well tolerated. In total, 46 patients (26/96 in the eculizumab arm, 20/47 in the placebo arm) were previously treated with the monoclonal antibody rituximab.
Objectives
To describe the efficacy and safety of eculizumab in patients in the PREVENT trial (NCT01892345) who had previously received rituximab.
Methods
Adults with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo with/without concomitant immunosuppressive treatment (except rituximab/mitoxantrone). A post hoc descriptive analysis was performed using data from patients with any prior rituximab treatment (within the previous year only for review of adverse events [AEs]) recorded more than 3 months before randomization.
Results
Baseline characteristics of the prior-rituximab subgroup were similar to those of the total PREVENT population; however, the subgroup included a lower proportion of Asian patients (10.9% vs 36.4% in total PREVENT) and greater representation from the Americas (58.7% vs 30.8%). In the subgroup, median times from last dose of rituximab to meningococcal vaccination and to first dose of study treatment were 31.7 and 38.7 weeks, respectively. Adjudicated relapses occurred in 1/26 patients (3.8%) and 7/20 patients (35.0%) in the eculizumab and placebo arms (hazard ratio: 0.093; 95% confidence interval: 0.011–0.755; p = 0.0055), respectively. Rates of AEs for eculizumab and placebo were 1025.8 and 1029.1 events/100 patient-years (100% of patients), respectively, and rates of serious AEs were 46.9 and 66.0 events/100 patient-years (38.9% and 47.1% of patients), respectively. Serious infections/infestations were recorded in 2/18 patients (11.1%) and 2/17 patients (11.8%) in the eculizumab and placebo arms, respectively.
Conclusions
In patients in PREVENT who had previously received rituximab, the risk of adjudicated relapse was significantly lower with eculizumab than with placebo. Rates of serious infections were similarly low with eculizumab and placebo.
Author Of 1 Presentation
P0752 - Safety of eculizumab in NMOSD and MG – analysis of the phase 3 studies PREVENT and REGAIN and their extensions (ID 554)
Abstract
Background
Aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD) and acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ gMG) are neurological disorders with complement involvement. Eculizumab (a terminal complement inhibitor) demonstrated efficacy in reducing relapse risk and in eliciting clinical improvements during the phase 3, randomized, double-blind PREVENT and REGAIN studies and their open-label extensions (OLEs) (NCT01892345/NCT02003144 [interim data, July 2019] and NCT01997229/NCT02301624) previously published.
Objectives
To compare infection rates in patients with AQP4+ NMOSD or AChR+ gMG receiving eculizumab or placebo with or without concomitant immunosuppressive therapy (IST) during PREVENT, REGAIN and their OLEs.
Methods
Patients were randomized to eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo. Concomitant ISTs, excluding rituximab, were permitted. Post hoc analysis was performed to examine rates of infections in these studies and for subgroups determined by number of ISTs received at baseline.
Results
Rates/100 patient-years (PY) and types of infection were similar in eculizumab and placebo groups. In patients with NMOSD, rates/100 PY and % (n/N), respectively, were: no IST: 176.1, 80.0% (28/35) vs 192.2, 61.5% (8/13); 1 IST: 171.5, 81.8% (45/55) vs 154.1, 63.6% (14/22); 2 ISTs: 186.7, 85.1% (40/47) vs 238.2, 83.3% (10/12). For patients with gMG, rates/100 PY and % (n/N), respectively, were: no IST: 236.8, 100.0% (2/2) vs 305.6, 50.0% (1/2); 1 IST: 228.8, 82.9% (34/41) vs 253.1, 50.0% (9/18); 2 ISTs: 170.5, 91.0% (71/78) vs 192.5, 58.5% (24/41); ≥ 3 ISTs: 97.5, 50.0% (1/2) vs 100.1, 50.0% (1/2). In patients with NMOSD or gMG receiving eculizumab vs placebo, serious infection rates/100 PY and % (n/N), respectively, were: no IST: 2.3, 5.7% (2/35) vs 8.0, 7.7% (1/13) and none observed (0/2 vs 0/2); 1 IST: 11.2, 16.4% (9/55) vs 7.0, 9.1% (2/22) and 16.2, 24.4% (10/41) vs 34.5, 5.6% (1/18); 2 ISTs, 14.8, 29.8% (14/47) vs 47.6, 25.0% (3/12) and 13.4, 21.8% (17/78) vs 24.1, 12.2% (5/41); ≥ 3 ISTs (gMG only), 13.9, 50.0% (1/2) vs 0.0, 0.0% (0/2). One patient with gMG (2 ISTs) had meningococcal meningitis that resolved with antibiotics and eculizumab was resumed.
Conclusions
In AQP4+ NMOSD and AChR+ gMG, infection rates/100 PY were similar in eculizumab and placebo groups, regardless of concomitant IST. Infection rates/100 PY were consistent with the established safety profile of eculizumab.