Objective:

To explore the impact of different strategies for handling rescue therapy on the treatment effect using data from the phase 3 PREVAIL trial (NCT05556096).

Background:

Generalized myasthenia gravis (gMG) trials commonly allow rescue therapy for clinical deteriorations or exacerbations. As patients are likely to benefit from rescue therapy, treatment effect estimates for the investigational treatment can potentially be confounded, especially when the frequency, duration, and timing of rescue therapy are not balanced across arms. Different strategies have been employed to address rescue therapy use and its impact on estimated treatment effects. 

Design/Methods:

Adults with anti-acetylcholine receptor antibody-positive gMG were randomized 1:1 to weekly subcutaneous self-administration of gefurulimab or placebo. The primary analysis estimated treatment effects using a treatment policy strategy. This post hoc analysis compared treatment effects in Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) total scores at week 26 using 3 methods to account for patients receiving rescue therapy: (1) imputation with the worst score of the same subject before rescue; (2) multiple imputations with the bottom 10% scores of the same treatment group; or (3) censored after rescue.

Results:

260 patients were randomized (gefurulimab, n=131; placebo, n=129). Demographics and baseline disease characteristics were balanced; rescue therapy was used by 5.3% and 12.4% of patients receiving gefurulimab and placebo, respectively. The primary analysis included all data in the analysis regardless of rescue therapy use; mean (SD) treatment difference was ‑1.6 (0.40) and -2.1 (0.50) for MG-ADL and QMG scores, respectively. The treatment difference varied with strategies 1-3 (mean [SD]: MG-ADL, -1.9 [0.42], -2.0 [0.42], and -1.9 [0.42]; QMG, -2.3 [0.51], -2.0 [0.52], and -2.1 [0.51]), all remained statistically significant.

Conclusions: