Clinical Outcomes and Cause of Death for Interferon Beta-1b Versus Placebo, 21 Years Following Randomization (P04.129)

Abstract

Objective: To evaluate the effect of IFNB-1b 250 µg (Betaseron®/Betaferon®) on long-term clinical outcomes in patients with MS at 21 yrs after the start of randomized treatment and identify the cause of death in patients who died. Background The 21-Year Long-Term Follow-Up (21-Y LTF) study identified the vital status of 98.4% (366/372) patients who participated in the pivotal IFNB-1b trial conducted between 1988 and 1993. Design/Methods: Originally, 372 patients were randomized to receive IFNB-1b 50 µg (n=125), IFNB-1b 250 µg (n=124), or placebo (n=123) every other day. Patients remained on randomized treatment during the trial for a median of 3.8 yrs (maximum 5.1 yrs), before licensed treatment became available. Clinical status of alive patients was assessed with a questionnaire, including a validated phone-based EDSS. Among patients who died, the cause of death and MS-relationship was determined by an adjudication committee masked to treatment assignment. Results: Original randomization to IFNB-1b 250 µg showed significant reduction (46.8%) in the risk of death over the 21-Y LTF period compared with placebo (log-rank, p=0.0173); the hazard ratio was 0.532. Clinical outcomes at 21-Y LTF were similar across the treatment arms. The categorical cause of death has been determined for 82.7% of deceased patients. Of the 67 assessed causes of death, 10 were CV disease/stroke, 6 cancer, 17 pulmonary infections, 11 accidental death/suicide, 21 MS, 1 multisystem dysfunction and 1 GI bleed. 78.3% of deaths were MS-related. Conclusions: With near-complete patient ascertainment (98.4%), an initial randomized control trial design, and the longest period of follow-up for a treatment-exposed MS population, these data provide insight into both the effects of IFNB-1b on survival/mortality in patients with MS and long-term clinical outcomes. The difference in mortality between placebo and active treatment appears to be MS-related. Also, cause of death due to pulmonary infections was more frequent in placebo compared to active treatment. Supported by: Bayer HealthCare Pharmaceuticals, Inc. Disclosure: Dr. Reder has received personal compensation from Abbott Laboratories, Immunoscience, Parsippany, NJ, American Medical Association, Astra Merck, Athena Neurosciences, Aventis Pharma, and Bayer.Dr. Reder has received personal compensation in an editorial capacity for Medlink/Neurobase electronic journal. Dr. Goodin has received personal compensation for activities with Merck Serono, Novartis, Berlex Laboratories, Bayer Pharmaceuticals Corporation, Biogen Idec, Schering AG and Teva Neuroscience as speaker, consultant and participant in clinical trials. Dr. Goodin has received research support from Novartis. Dr. Ebers has received personal compensation for activities with Bayer HealthCare Pharmaceuticals as a consultant. Dr. Cutter has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals, Inc., Cleveland Clinic, Daiichi Pharmaceutical Corporation, GlaxoSmithKline, Inc., Genmab Biopharmaceuticals, Eli Lilly & Company, Medivation, Modigenetech, Ono Pharmaceutical, PTC Therapeutics, Teva Neuroscience, Vivus, University of Pennsylvania, NHLBI, NINDS, NMSS, Alexion, Bayhill Therapeutics, Bayer Pharmaceuticals Corporation, Celgene, Novartis, Consortium of MS Centers, Genzyme Corporation, Klein-Buendel Incorporated, Nuron Biotech, Peptimmune, Somnus Pharmaceuticals, Sandoz, University of Texas Southwestern and Visioneering Technologies, Inc. Dr. Cutter has received compensation for serving on the board of Pythagoras, INC. Dr. Cutter has received research support from various pharmaceutical corporations. Dr. Kremenchutzky has received personal compensation for activities with MS Society of Canada, the End MS Research and Training Network, the Research Scientific Foundation of the MS Society of Canada, and the Canadian Institute of Health Research, Bayer Pharmaceuticals, Biogen Idec, Serono, Inc., Genzyme Corporation, Novartis, Sanofi-Aventis Pharmaceuticals, and Teva Neuroscience as a speaker, researcher and/or consultant. Dr. Kremenchutzky has received research support from MS Society of Canada, Bayer Pharmaceuticals Corporation, Biogen Idec, Serono, Inc., Teva Neuroscience, Genetech, Inc., and Novartis. Dr. Oger has received personal compensation for activities with Aspreva, Sanofi-Aventis Pharmaceuticals, Inc., Bayer Pharmaceuticals Corporation, Biogen Idec, EMD Serono, Genentech, Inc., Schering, Talecris, and Teva Neuroscience. Dr. Oger has received research support to his University to use Biacore to evaluate neutralizing antibodies to interferon. Dr. Langdon has received personal compensation for activities with Bayer Schering Pharma, AG/Bayer HealthCare Pharmaceuticals, Biogen, Hoffman La Roche, Merck Serono, Novartis, Sanofi-Aventis and Serono Symposia.Dr. Langdon has received research support from Bayer HealthCare, Merck Serono and Novartis. Mr. Rametta has received personal compensation for activities with Bayer Health Care Pharmaceuticals as an employee. Dr. Beckmann has received personal compensation for activities with Bayer Pharmaceuticals Corporation as an employee. Dr. Knappertz has received personal compensation for activities with Bayer Pharmaceuticals Corporation as an employee.