New Versus Old: Long-Term Comparative Effectiveness Research Projections for Disease Modifying Therapies in Relapse-Remitting Multiple Sclerosis (P06.196)

Objective: To estimate the long-term comparative effectiveness research (CER) of first-line treatment with glatiramer acetate (GA), fingolimod, or natalizumab, for relapse-remitting multiple sclerosis (RRMS). Background No randomized controlled trial (RCT) compares all disease modifying therapies (DMT) for RRMS. Further, RCTs lack evidence on long-term (> 2 years) clinical outcomes. Clinical equipoise suggests a critical need to estimate CER evidence among older and newer DMTs. Design/Methods: We developed a simulation model to estimate the average 20-year comparative effectiveness of GA, fingolimod, and natalizumab for a cohort of 30 year olds with RRMS. Key inputs to the model included published natural history progressions within the Expanded Disability Status Scale (EDSS), treatment effects from RCTs on slowing disease progression and reducing relapse rates, risk of progressive multifocal leukoencephalopathy (PML), and utility preference scores. Outputs were DMT-specific long-term harm (PML risk) and benefits (average relapse rate and time to disability (EDSS ≥ 7)) and quality-adjusted life years (QALYs). Results: For treatment duration of 20 years, average per-patient relapses were: 8.8, 5.9, and 4.1, average time (years) to disability was: 18.4, 18.9, 19.0, for GA, fingolimod, and natalizumab respectively. Average QALYs were: 11.1, 11.8, and 12.1 for GA, fingolimod, and natalizumab respectively. Compared to GA, fingolimod resulted in 2.9 fewer relapses, 0.5 more years of disability free time, and an incremental 0.7 QALYs gained. Compared to GA, natalizumab resulted in 4.6 fewer relapses, 0.6 more years of disability free time, 0.017 more cases of PML per treated patient, and an incremental 1.0 QALYs gained. Conclusions: Long-term clinical benefit outcomes were favored by natalizumab treatment, but must be weighed against an increased risk of PML. The QALY outcome, a composite measure that incorporates both benefits and harms, was favored by natalizumab treatment. CER models like this can be used to compare all DMTs to provide projections about long-term harms and benefits. Supported by: Funded in part by The Agency for Healthcare Research and Quality as part of the Colorado Comparative Effectiveness Research K12 Training Program: K12 HS019464. Disclosure: Dr. Campbell has received personal compensation for activities with Veritech Inc and Amgen Inc for consulting services. Dr. McQueen has nothing to disclose. Dr. Corboy has received personal compensation for activities with ProCE, Celgene Therapeutics, and Teva Neuroscience. Dr. Corboy has received personal compensation in an editorial capacity for Neurology in Clinical Practice. Dr. Corboy has received research from BioMS, Genentech, Inc., Orasi Medical, Eli Lilly & Company, Celgene Therapeutics, and Immune Tolerance Network. Dr. Vollmer has received personal compensation for activities with Teva Neuroscience, Daiichi Pharmaceutical Corporation, Eli Lilly & Company, Sanofi-Aventis Pharmaceuticals, Inc., PRIME Education, Inc., Projects in Knowledge, Guidepoint Global, Eisai Inc., Biogen Idec, Xenoport, Novartis, Schering-Plough Biopharma, Ono Pharmaceutical, Elan Corporation, Acorda, IMPAX, GlaxoSmithKline, Inc., and EMD Serono. Dr. Vollmer has recieved research support from EMD Serono, Teva Neuroscience, Novartis, Daiichi Pharmaceutical Corporation, Genzyme Corporation, Ono Pharmaceutical, Eli Lilly & Company, Sanofi-Aventis Pharmaceuticals, Inc., IMPAX, and Biogen Idec. Dr. Nair received has received personal compensation for activities with Centercor as a consultant.