Baseline Predictors of Disease Activity in Patients with CIS Treated with Interferon beta-1b in the BENEFIT 11 Trial (P2.121)

Objective: To analyze baseline patient characteristics for prediction of disease outcomes 11 years postrandomization. Background: A number of variables have been identified that are assessable early in the course of MS that may predict the disease course. Long-term follow up from the BENEFIT trial, which enrolled patients with clinically-isolated syndrome, is a unique opportunity to assess the predictive capacity of these variables. Methods: Patients were randomized to initial treatment with interferon beta-1b or placebo for 2 years or until diagnosis of clinically-definite multiple sclerosis (CDMS), after which they could take interferon beta-1b. Regression analyses including baseline age; sex; mono/multifocal onset; steroid treatment, EDSS score; gadolinium-enhancing (Gd+) and T2 lesion numbers; T2 and T1 hypointense lesion volume; presence of lesions in the spinal cord, optic nerve, or brainstem; PASAT score, and treatment assignment as covariates were conducted. P<.05 was used to identify significant associations. Results: 278 of 468 originally-randomized patients in BENEFIT were assessed at Year 11 (167, early treatment; 111, delayed treatment). In regression models, early treatment with interferon beta-1b, older age, lower number of Gd+ lesions, smaller T1 lesion volume, absence of steroid treatment, and absence of spinal cord lesions were significantly associated with longer time to CDMS. Older age, and male sex were associated with lower annualized relapse rate. Younger age, male sex, higher baseline EDSS, and lower Gd+ lesion count significantly predicted lower probability of a sustained 1-point EDSS progression. Higher likelihood of presence of clinical disease (≥1 relapse, CDMS, or EDSS progression) at Year 11 was significantly associated with higher number of Gd+ lesions. Conclusion: Analyses of patients after 11 years identified a number of baseline demographic, MRI, and clinical variables that predicted longer-term disease outcomes. Among other factors, assignment to earlier treatment with interferon beta-1b was associated with longer time to CDMS. Disclosure: MS Freedman has received compensation from Bayer HealthCare, Biogen Idec, EMD Canada, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, and Teva Canada Innovation for consulting services. Dr. Kappos9s institution (University Hospital Basel) has received royalty payments from Neurostatus Systems GmbH. Dr. Edan has nothing to disclose. Dr. Montalban has received personal compensation for activities with Actelion, Almirall, Bayer Pharmaceuticals, Biogen Idec, Genzyme Corporation, Merck & Co., Inc., NeuroTex, Novartis, Octopharma, Receptos, and Roche Diagnostics Corporation as a speaker. Dr. Hartung has received personal compensation for activities with from Bayer, Biogen, GeNeuro, Genzyme as speaker, committee member, consultant. Dr. Hemmer has received personal compensation for activities with Roche, Novartis, Bayer Schering, Merck Serono, Biogen Idec, GSK, Chugai, Micromet and Genzyme Corporation as a scientific advisory board member. Dr. Fox has received research support from Biogen, Chugai, Eli Lily, EMD Serono, Genzyme, Novartis, Opexa, Roche. Dr. Barkhof has received personal compensation for activities with Bayer Schering Pharma, Biogen Idec, Genzyme, Janssen Research, Merck Serono, Novartis, Roche, Sanofi, Synthon BV, and Teva as a consultant. Dr. Schippling has received personal compensation for activities with Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, Teva, and Sanofi-Aventis as consultant and speaker. R. Koelbach has received personal compensation for activities with PAREXEL International as an employee. Dr. Pleimes has received personal compensation for activities with Myelo Therapeutics GmbH as an employee, and Bayer Pharmaceuticals Corporation as an employee and consultant. Dr. Suarez has received personal compensation for activities with Bayer Pharma AG/Bayer HealthCare Pharmaceuticals as an employee. Dr. Wicklein has received personal compensation for activities with Bayer Pharmaceuticals Corporation as an employee.