Abstract Details

Title Rescue Therapy Handling and Treatment Effect Estimates: A Post Hoc Analysis From the PREVAIL Trial of Gefurulimab in gMG

Topic Autoimmune Neurology

Presentation(s) P2 - Poster Session 02 (3:00 PM-4:00 PM)

Poster/Presentation
Number 1-016

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

Estimated treatment effects varied with rescue therapy handling methodology, highlighting the need to account for rescue therapies when interpreting trial results to prevent bias and inappropriate conclusions.

Authors/Disclosures
Tuan H. Vu, MD (University of South Florida) PRESENTER	Dr. Vu has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Dianthus. Dr. Vu has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amgen. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NMD Pharma. Dr. Vu has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ARGENX. Dr. Vu has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen (Horizon). Dr. Vu has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Johnson & Johnson. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda. Dr. Vu has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for VOR. Dr. Vu has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Alexion. Dr. Vu has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for CSL Behring. Dr. Vu has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Argenx. Dr. Vu has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Johnson & Johnson. Dr. Vu has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Amgen. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. The institution of Dr. Vu has received research support from Alexion. The institution of Dr. Vu has received research support from RA Pharma/UCB. The institution of Dr. Vu has received research support from ARGENX. The institution of Dr. Vu has received research support from Horizon/Amgen. The institution of Dr. Vu has received research support from CSL Behring. The institution of Dr. Vu has received research support from Cartesian Therapeutics. The institution of Dr. Vu has received research support from Janssen/Johnson & Johnson. The institution of Dr. Vu has received research support from Immunovant. The institution of Dr. Vu has received research support from Regeneron. The institution of Dr. Vu has received research support from Dianthus. The institution of Dr. Vu has received research support from COUR. The institution of Dr. Vu has received research support from NMD Pharma. The institution of Dr. Vu has received research support from VOR. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving as a Faculty with AcademicCME. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving as a Faculty with CMEO. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving as a Faculty with PER. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving as a Faculty with MedLive.
Shulian Shang, PhD	Dr. Shang has received personal compensation for serving as an employee of Alexion, AstraZeneca Rare Disease. Dr. Shang has stock in Alexion, AstraZeneca Rare Disease.
Francesco Sacca, MD, FAAN (University Federico II)	Dr. Sacca has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion. Dr. Sacca has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Argenx. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lexeo. Dr. Sacca has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genpharm. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medpharma. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Madison Pharma. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zai Lab. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dianthus. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Reata. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neopharm Israel. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Johnson&Johnson. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Sacca has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Astrazeneca. The institution of Dr. Sacca has received research support from AIFA. The institution of Dr. Sacca has received research support from FARA.

��ɫ��

��ɫ��