Relapse recovery in relapsing-remitting multiple sclerosis: An analysis of the CombiRx dataset.

BACKGROUND

Clinical relapses are the defining feature of relapsing forms of multiple sclerosis (MS), but relatively little is known about the time course of relapse recovery.

OBJECTIVE

The aim of this study was to investigate the time course of and patient factors associated with the speed and success of relapse recovery in people with relapsing-remitting MS (RRMS).

METHODS

Using data from CombiRx, a large RRMS trial (clinicaltrials.gov identifier NCT00211887), we measured the time to recovery from the first on-trial relapse. We used Kaplan-Meier survival analyses and Cox regression models to investigate the association of patient factors with the time to unconfirmed and confirmed relapse recovery.

RESULTS

CombiRx included 1008 participants. We investigated 240 relapses. Median time to relapse recovery was 111 days. Most recovery events took place within 1 year of relapse onset: 202 of 240 (84%) individuals recovered during follow-up, 161 of 202 (80%) by 180 days, and 189 of 202 (94%) by 365 days. Relapse severity was the only factor associated with relapse recovery.

CONCLUSION

Recovery from relapses takes place up to approximately 1 year after the event. Relapse severity, but no other patient factors, was associated with the speed of relapse recovery. Our findings inform clinical practice and trial design in RRMS.

Déclaration de conflit d'intérêts

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr M.W.H. received consulting fees and travel support from Biogen, Novartis, Roche, Sanofi Genzyme, and EMD Serono. Dr E.M. received honoraria as consultant in advisory boards, and as chairperson or lecturer in meetings, or travel support from Actelion, Almirall, Bayer, Biogen Idec, Bristol Myers Squibb, Merck Serono, Teva, Novartis, Roche, and Sanofi Genzyme. Dr L.B. received honoraria from serving as a speaker and as a consultant in advisory boards from Bayer, Teva, Celgene, Biogen, Sanofi, Merck Serono, Novartis, Roche, Almirall, Bristol Myers Squibb, and Janssen. Dr J.M. reports no disclosures. Dr E.M.M.S. reports no disclosures. Dr J.C. reports no disclosures. Dr P.R. received consulting and speaking honoraria from Alexion, Banner, Biogen, Bristol Myers Squibb, Genentech, Genzyme, Horizon, and TG Therapeutics. Dr J.D.B. received honoraria from serving on the scientific advisory board and speaker’s bureau of Biogen, Celgene, EMD Serono, Genentech, and Novartis. He has received research support from AbbVie Inc., Alexion, Alkermes, Biogen, Celgene, Sanofi Genzyme, Genentech, Novartis, and TG Therapeutics. Dr J.S.W. received compensation for consulting, scientific advisory boards, or other activities with Avotres, Brainstorm Cell Therapeutics, Cleveland Clinic Foundation, EMD Serono, Inmagine, Novartis/Sandoz, Roche/Genentech; royalties are received through UTHealth for out-licensed monoclonal antibodies to Millipore (Chemicon International) Corporation. Dr F.D.L. received honoraria from consulting agreements and from serving on scientific advisory boards and data safety and monitoring boards and speaker’s bureau of Biogen, EMD Serono, Novartis, Teva, Actelion/Janssen, Sanofi/Genzyme, Acorda, Roche/Genentech, MedImmune/Viela Bio, Receptos/Celgene/BMS, TG Therapeutics, MedDay, Atara Biotherapeutics, Mapi Pharma, Innate Immunotherapeutics, Apitope, Orion Biotechnology, Brainstorm Cell Therapeutics, Jazz Pharmaceuticals, GW Pharma, Mylan, Immunic, Population Council, Avotres, and Neurogene. He received research funding from Novartis, Actelion, Biogen, Sanofi, NMSS, NIH, Brainstorm Cell Therapeutics. He holds stock options of Avotres. Prof G.C. served on Data and Safety Monitoring Boards: Astra-Zeneca, Avexis Pharmaceuticals, Biolinerx, Brainstorm Cell Therapeutics, Bristol Myers Squibb/Celgene, CSL Behring, Galmed Pharmaceuticals, Horizon Pharmaceuticals, Hisun Pharmaceuticals, Mapi Pharmaceuticals LTD, Merck, Merck/Pfizer, Opko Biologics, OncoImmune, Neurim, Novartis, Orphazyme, Sanofi-Aventis, Reata Pharmaceuticals, Teva Pharmaceuticals, Viela Bio Inc., Vivus, NHLBI (Protocol Review Committee), NICHD (OPRU oversight committee). Consulting or Advisory Boards: Biodelivery Sciences International, Biogen, Click Therapeutics, Genzyme, Genentech, GW Pharmaceuticals, Immunic, Klein-Buendel Incorporated, MedImmune, MedDay, Neurogenesis LTD, Novartis, Osmotica Pharmaceuticals, Perception Neurosciences, Recursion/Cerexis Pharmaceuticals, Roche, TG Therapeutics. Dr G.C. is employed by the University of Alabama at Birmingham and President of Pythagoras, Inc., a private consulting company located in Birmingham AL.