Abstract
Background In the Phase 3 RAISE study (NCT04115293), zilucoplan significantly improved myasthenia gravis (MG)-specific outcomes in patients with acetylcholine receptor autoantibody-positive generalised MG. After the first 12 weeks of the ongoing, open-label extension study, RAISE-XT (NCT04225871), corticosteroid dose could be changed per the investigator’s discretion. Here, we evaluate changes in corticosteroid dose during treatment with zilucoplan in RAISE-XT.
Methods RAISE-XT enrolled adults who completed the Phase 2 or RAISE studies. Patients self-administered daily subcutaneous zilucoplan 0.3mg/kg, either continuing with zilucoplan or switching from placebo. Primary outcome was incidence of treatment-emergent adverse events (TEAEs). We assessed (post hoc) the proportion of patients who discontinued/reduced or increased corticosteroid dose relative to double-blind baseline up to Week 60. Change from baseline (CFB) in MG Activities of Daily Living (MG-ADL) score was described for each category.
Results 200 patients enrolled. At Week 60, 30% (n=18/60) and 22% (n=12/54) of patients receiving corticosteroids in the zilucoplan and placebo-switch groups, respectively, reduced or discontinued corticosteroids (mean reductions: 14mg and 16mg). Among these patients, mean (standard deviation [SD]) CFB in MG-ADL score was −5.00 (3.96) and −5.67 (6.89). At Week 60, 12% (n=7/60) and 7% (n=4/54) of patients in the zilucoplan and placebo-switch groups, respectively, increased corticosteroid dose (~12mg mean increase in both groups) with mean (SD) CFB in MG-ADL score of −4.86 (2.55) and −9.75 (4.57). TEAEs occurred in 188 (94.0%) patients (data cut-off: 08 September 2022).
Conclusions While receiving zilucoplan, discontinuation or dose reduction in concomitant corticosteroids was possible with maintained efficacy.
