Xiangyi Meng1, Peter S Chin2, Ron Hashmonay3, M Zahur Islam4, Gary Cutter5. 1. Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936-1080, United States. Electronic address: xiangyi.meng@novartis.com. 2. Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936-1080, United States. Electronic address: Peter.chin@novartis.com. 3. Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936-1080, United States. Electronic address: Ronny.hashmonay@novartis.com. 4. Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936-1080, United States. Electronic address: zahur.islam@novartis.com. 5. Department of Biostatistics, University of Alabama at Birmingham School of Public Health, Birmingham, AL 35294-0022, United States. Electronic address: cutterg@prodigy.net.
Abstract
BACKGROUND: In the absence of controlled, parallel-group studies, statistical methods developed to estimate treatment effects in patients receiving alternative/rescue treatment in clinical trials may be used to estimate the effects of multiple sclerosis (MS) therapy switch using available clinical trial data. OBJECTIVE: To use TRANSFORMS data and parametric models to assess the time to first confirmed relapse in MS patients who switched from intramuscular interferon β-1a (IFNβ-1a IM) 30 μg/mL once weekly to oral fingolimod 0.5 or 1.25mg once daily vs. remaining on IFNβ-1a IM. METHODS: Post hoc analyses were conducted using data from the intent-to-treat population. The Branson and Whitehead switch model with iterative parameter estimation was used to estimate the ratio of the observed time to first confirmed relapse over the estimated time. RESULTS: Log-linear regression model results showed that fingolimod 0.5 and 1.25mg prolonged time to relapse, with an estimated median time to first relapse of 5.07 years (P=0.0026 vs. IFNβ-1a IM) and 4.11 years (P=0.0113), respectively, versus 2.26 years with IFNβ-1a IM. The estimated ratio of observed time to first confirmed relapse to the estimated time had the patient remained on IFNβ-1a IM was 2.09 (95% CI, 1.45-3.04) for switching to fingolimod 0.5mg and 1.84 (95% CI, 1.30-2.65) for switching to fingolimod 1.25mg. CONCLUSION: During the extension, time to first confirmed relapse was approximately doubled in patients switching from IFNβ-1a IM to fingolimod. These analytic methods may be useful in evaluating treatment switch effects in clinical trials with extension data.
RCT Entities:
BACKGROUND: In the absence of controlled, parallel-group studies, statistical methods developed to estimate treatment effects in patients receiving alternative/rescue treatment in clinical trials may be used to estimate the effects of multiple sclerosis (MS) therapy switch using available clinical trial data. OBJECTIVE: To use TRANSFORMS data and parametric models to assess the time to first confirmed relapse in MSpatients who switched from intramuscular interferon β-1a (IFNβ-1a IM) 30 μg/mL once weekly to oral fingolimod 0.5 or 1.25mg once daily vs. remaining on IFNβ-1a IM. METHODS: Post hoc analyses were conducted using data from the intent-to-treat population. The Branson and Whitehead switch model with iterative parameter estimation was used to estimate the ratio of the observed time to first confirmed relapse over the estimated time. RESULTS: Log-linear regression model results showed that fingolimod 0.5 and 1.25mg prolonged time to relapse, with an estimated median time to first relapse of 5.07 years (P=0.0026 vs. IFNβ-1a IM) and 4.11 years (P=0.0113), respectively, versus 2.26 years with IFNβ-1a IM. The estimated ratio of observed time to first confirmed relapse to the estimated time had the patient remained on IFNβ-1a IM was 2.09 (95% CI, 1.45-3.04) for switching to fingolimod 0.5mg and 1.84 (95% CI, 1.30-2.65) for switching to fingolimod 1.25mg. CONCLUSION: During the extension, time to first confirmed relapse was approximately doubled in patients switching from IFNβ-1a IM to fingolimod. These analytic methods may be useful in evaluating treatment switch effects in clinical trials with extension data.
Authors: Bianca Weinstock-Guttman; Robert Bermel; Gary Cutter; Mark S Freedman; Thomas P Leist; Xiaoye Ma; Deidre Kile; Bruno Musch; Anthony T Reder; Jerry S Wolinsky Journal: Mult Scler Date: 2021-08-12 Impact factor: 6.312