Abstract Details

Title Relapse Activity in the CombiRx Trial: Blinded, 7-Year Extension Results

Topic MS and Related Diseases

Presentation(s) S01 - (-)

Poster/Presentation
Number 002

Background CombiRx was a double-blind, placebo-controlled, multi-center randomized clinical trial comparing combined interferon beta-1a (IFN) 30ug IM weekly and glatiramer acetate (GA) 20mg daily to each agent alone in relapsing-remitting multiple sclerosis (RRMS). Entry criteria, demographics and the three year clinical and MRI results have been previously presented.

Objective

Design/Methods 1008 participants were randomized and followed until the last participant enrolled completed 3 yrs. At trial completion, 80.1% completed 3 years and 84.4% continued into the extension. Exacerbation types were based on stringency of confirmation of EDSS change: Protocol Defined Exacerbation (PDE) within 7 days, Non-PDE (NPDE) outside 7 days.

Results Average years on study was 3.9, not different by treatment. ARRs by treatment for PDE were IFN+GA: 0.10, IFN: 0.13, GA: 0.09; with age adjusted HR of 1.37 for IFN vs GA (p=0.03), 0.78 IFN+GA vs IFN (p=0.02), and 1.07 IFN+GA vs GA (p=0.32); and for PDE+NPDE were IFN+GA: 0.19, IFN: 0.25, GA: 0.18; with HR of 1.32 for IFN vs GA (p=0.01), 0.75 for IFN+GA vs IFN (p=0.001), and 1.01 for IFN+GA vs GA (p=0.45).

Conclusions This study provides the longest blinded phase III RRMS follow up results. The 3-year ARR results previously reported were low for all treatment cohorts with the combination and GA groups having the lowest ARR. Similar patterns are seen in this long term extension cohort. Relapse rates drop over the course of the study to exceedingly low values. Both the combination group and GA continue to be superior to IFN. In the core study, MRI activity was significantly higher in the combination group. Despite that, long term follow up did not reveal a delayed clinical benefit in the combination group.

Authors/Disclosures
Fred D. Lublin, MD, FAAN (Icahn School of Medicine At Mount Sinai) PRESENTER	Dr. Lublin has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche/Genentech. Dr. Lublin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Lublin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurogene. Dr. Lublin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Lublin has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medimmune/Viela Bio/Horizon. Dr. Lublin has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Receptos/Celgene/BMS. Dr. Lublin has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic. Dr. Lublin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Labcorp. Dr. Lublin has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neuralight. Dr. Lublin has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Entelexo. Dr. Lublin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dr. Lublin has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avotres. Dr. Lublin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Lublin has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Lublin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for EMD Serono. Dr. Lublin has received personal compensation in the range of $100,000-$499,999 for serving as an Expert Witness for Multiple entities. Dr. Lublin has stock in Avotres. Dr. Lublin has stock in Neuralight. The institution of Dr. Lublin has received research support from Brainstorm. The institution of Dr. Lublin has received research support from biogen. The institution of Dr. Lublin has received research support from NIH.
Stacey Cofield	No disclosure on file
	No disclosure on file
Gary R. Cutter, PhD (University of Alabama At Birmingham)	Dr. Cutter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biodelivery Sciences International, Biogen, Click Therapeutics, Genzyme, Genentech, GW Pharmaceuticals, Immunic, Klein-Buendel Incorporated, Medimmune/Viela Bio, Medday, Merck/Serono, Neurogenesis LTD, Novartis, Osmotica Pharmaceuticals, Perception Neurosciences, Recursion/Cerexis Pharmaceuticals, Regeneron, Reckover Pharmaceuticals, Roche, TG Therapeutics.. Dr. Cutter has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Applied Therapeutics, AI therapeutics, AMO Pharma, Astra-Zeneca, Avexis Pharmaceuticals, Biolinerx, Brainstorm Cell Therapeutics, Bristol Meyers Squibb/Celgene, CSL Behring, Galmed Pharmaceuticals, Green Valley Pharma, Horizon Pharmaceuticals, Immunic, Karuna Therapeutics, Mapi Pharmaceuticals LTD, Merck, Mitsubishi Tanabe Pharma Holdings, Opko Biologics,Prothena Biosciences, Novartis, Regeneron, Sanofi-Aventis, Reata Pharmaceuticals, NHLBI (Protocol Review Committee), University of Texas Southwestern, University of Pennsylvania, Visioneering Technologies, Inc.. Dr. Cutter has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JASN.
Amber Salter, PhD (UT Southwestern Medical Center)	Dr. Salter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gryphon Bio. Dr. Salter has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abata Therapeutics. Dr. Salter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sora Neuroscience. Dr. Salter has stock in Owl Therapeutics. The institution of Dr. Salter has received research support from National Multiple Sclerosis Society. The institution of Dr. Salter has received research support from Department of Defense Congressionally Directed Medical Research Program. The institution of Dr. Salter has received research support from Consortium of Multiple Sclerosis Centers. The institution of Dr. Salter has received research support from Multiple Sclerosis Society of Canada.
	No disclosure on file
Robin A. Conwit, MD, FAAN	Dr. Conwit has nothing to disclose.
	No disclosure on file
Flavia Nelson, MD (University of Miami, Miller School of Medicine)	Dr. Nelson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Brystol Meyer Squib. Dr. Nelson 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. Dr. Nelson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Genetech. The institution of Dr. Nelson has received research support from NIH.
Tarah Gustafson	No disclosure on file
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.
	No disclosure on file

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