Abstract Details

Title Pre-Defined Subgroups Analyses of TOWER, a Placebo-Controlled Phase 3 Trial of Teriflunomide in Patients with Relapsing Multiple Sclerosis

Topic MS and Related Diseases

Presentation(s) S41 - (-)

Poster/Presentation
Number 006

Objective

Background Teriflunomide is a novel, once-daily, oral, disease-modifying therapy recently approved within the US for treatment of relapsing multiple sclerosis (RMS). In TOWER, teriflunomide 14mg significantly reduced annualized relapse rate (ARR) by 36.3% (p<0.001) and sustained disability progression (confirmed for at least 12 weeks) by 31.5% (p=0.044) compared with placebo. A significant reduction in ARR (22.3%; p=0.018) was observed with teriflunomide 7mg, with no significant effect on 12-week disability progression.

Design/Methods In TOWER, 1169 patients with RMS (18-55 years old, Expanded Disability Status Scale [EDSS] score ?5.5 at screening, and ?1 or ?2 relapses in the 12 or 24 months before randomization, respectively) were randomized to once-daily placebo, teriflunomide 7mg or 14mg. The primary and key secondary endpoints were ARR and 12-week disability progression. Subgroup analyses were performed for these endpoints according to pre-defined baseline demographics and disease characteristics, including baseline EDSS strata, number of relapses within the past 1 and 2 years, MS subtype, and previous use of MS drugs. A generalized estimating equation (GEE) method was used to assess consistency of treatment effect across subgroups levels, utilizing a treatment-by-subgroup interaction test for each factor separately.

Results The efficacy of teriflunomide on ARR was consistent across the pre-defined subgroups. A consistent treatment effect of teriflunomide 14mg on disability progression was observed across the pre-defined subgroups, with the exception of subgroups defined by gender (p=0.017) and number of relapses within the past 1 (p=0.018) and 2 years (p=0.045).

Conclusions The beneficial effect of teriflunomide vs placebo on ARR was consistent across subgroups while the beneficial effect of teriflunomide 14mg on disability progression was more pronounced in patients with >1 relapse within the past 1 and 2 years prior to randomization.

Authors/Disclosures
Harold Moses, MD (Vanderbilt Multiple Sclerosis Center) PRESENTER	No disclosure on file
Antonio Bertolotto, MD, FAAN (Ospedale Koelliker)	Dr. Bertolotto has nothing to disclose.
Mark S. Freedman, MD, FAAN (University of Ottawa)	Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Actelion(Janssen/J&J). Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BiogenIdec. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS/Celgene. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Inc. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Actelion (Janssen/J&J). Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Atara Biotherapeutics. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer Healthcare. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for BiogenIdec. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Clene Nanomedicine. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GRI Bio. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Magenta Therapeutics. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck Serono. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. Freedman has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi Genzyme. Dr. Freedman has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. The institution of Dr. Freedman has received research support from Sanofi Genzyme.
Ludwig Kappos, MD, FAAN (RC2NB, University Hospital Basel)	The institution of Dr. Kappos has received research support from Bayer. The institution of Dr. Kappos has received research support from Biogen. The institution of Dr. Kappos has received research support from Genentech. The institution of Dr. Kappos has received research support from Genzyme. The institution of Dr. Kappos has received research support from Janssen. The institution of Dr. Kappos has received research support from Merck Serono. The institution of Dr. Kappos has received research support from Minoryx. The institution of Dr. Kappos has received research support from Novartis. The institution of Dr. Kappos has received research support from Roche. The institution of Dr. Kappos has received research support from Sanofi. The institution of Dr. Kappos has received research support from Santhera. The institution of Dr. Kappos has received research support from Swiss MS Society, Swiss National Research Foundation, European Union, Roche Research Foundation, Innosuisse. The institution of Dr. Kappos has received research support from Shionogi. The institution of Dr. Kappos has received research support from Japan Tobacco. The institution of Dr. Kappos has received research support from Auriga Vision AG. The institution of Dr. Kappos has received research support from EMD Serono. The institution of Dr. Kappos has received research support from Glaxo Smith Kline. The institution of Dr. Kappos has received research support from Wellmera AG. The institution of Dr. Kappos has received research support from Eli Lilly (Suisse) SA. The institution of Dr. Kappos has received research support from Bristol Myers Squibb. The institution of Dr. Kappos has received research support from Celltrion Inc. Dr. Kappos has received intellectual property interests from a discovery or technology relating to health care.
Aaron E. Miller, MD, FAAN (Mt Sinai School Of Med)	Dr. Miller has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Accordant Health Services (Caremark). Dr. Miller has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Corevitas (formerly known as Corrona). Dr. Miller has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for MAPI=Pharma. Dr. Miller has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Viatris (Mylan). Dr. Miller has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Guidepoint Global. Dr. Miller has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gerson Lehrman Group. Dr. Miller has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen Idec. Dr. Miller has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alexion. Dr. Miller has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Amgen (Horizon Therapeutics). Dr. Miller has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for Sterne Kessler. Dr. Miller has received publishing royalties from a publication relating to health care.
Tomas Olsson, MD, PhD (Karolinska Institutet)	Prof. Olsson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Prof. Olsson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Prof. Olsson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Prof. Olsson has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. The institution of Prof. Olsson has received research support from Biogen. The institution of Prof. Olsson has received research support from Novartis. The institution of Prof. Olsson has received research support from Sanofi. The institution of Prof. Olsson has received research support from Merck.
Jerry S. Wolinsky, MD, FAAN (McGovern Medical School, UTHealth)	Dr. Wolinsky has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avotres. Dr. Wolinsky has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Brainstorm Cell Therapeutics. Dr. Wolinsky has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cleveland Clinic Foundation. Dr. Wolinsky has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Wolinsky has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Inmagene. Dr. Wolinsky has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis/Sandoz. Dr. Wolinsky has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Wolinsky has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. Dr. Wolinsky has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for University of Alabama Birmingham. Dr. Wolinsky has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Wolinsky has received intellectual property interests from a discovery or technology relating to health care. Dr. Wolinsky has received intellectual property interests from a discovery or technology relating to health care.
Christian Confavreux, MD (Hospital Antiquaille)	No disclosure on file
Giancarlo Comi, MD (University Vita-Salute)	Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Janssen. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Aspen Healthcare. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Sanofi. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Rewind.
Teresa Bagulho, MD (Sanofi-Aventis)	No disclosure on file
	No disclosure on file
Philippe Truffinet, MD (Sanofi)	Dr. Truffinet has received personal compensation for serving as an employee of Sanofi.
Paul W. O'Connor, MD	No disclosure on file

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