Lower Long-Term Disability with Early Start of High-Efficacy Therapies in Multiple Sclerosis

Objective: To compare patients’ long-term disability following early vs later commencement of high-efficacy therapies for relapsing remitting multiple sclerosis (MS). Background: The availability of numerous highly efficacious therapies for MS has ignited debate about whether early aggressive treatment is more favourable than escalation after failure of first line therapies. Design/Methods: Using international MS registries (MSBase, Cambridge University), we identified patients with relapsing remitting MS who commenced high-efficacy therapies (Rituximab, Ocrelizumab, Mitoxantrone, Alemtuzumab, Natalizumab) either 0–2 years (early) or >4 years (late) after clinical disease onset. Indication bias was minimised by propensity score matching on demographic and clinical variables in the first two years of disease. Outcomes were assessed at years 6 to 10 after disease onset. The primary outcome was difference in disability, as measured by the Expanded Disability Status Score (EDSS). Secondary outcomes were cumulative hazard of confirmed disability progression and hazard of treatment discontinuation. Results: 117 patients in the early group were matched to 181 in the late group. At baseline, the mean (SD) EDSS was 2.4 (1.2) in both groups. Median (IQR) followup time was 7.4 (6.4–8.6) years. In the sixth year, the EDSS was 2.4 (1.3) in the early group and 3. 3(1.2) in the late group (p 0.5 EDSS steps) and statistically significant 10 years after disease onset. During years 0–2, the early group had a higher cumulative hazard of confirmed disability progression; the inverse is true from year 2 to 10. Conclusions: Patients with MS commencing high-efficacy immunotherapy early after disease onset accumulate less long-term disability compared to those exposed later in their disease. Those treated earlier had a more active disease course initially, which was then mitigated by their early aggressive management strategy. In patients with highly active MS, early exposure to high efficacy therapies is recommended. Disclosure: Dr. He has nothing to disclose. Dr. Merkel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Brown has nothing to disclose. Dr. Zhovtis Ryerson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Zhovtis Ryerson has received personal compensation for serving on speaker bureau for Biogen, Teva, Genentech and advisory board for Biogen and Celgene. Dr. Zhovtis Ryerson has received research support from Biogen. Dr. Kister has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Has served on advisory boards of Biogen, Genentech.Dr. Malpas has nothing to disclose. Dr. Horakova has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Merck, Teva, Roche, Sanofi Genzyme, and Novartis. Dr. Horakova has received research support from Biogen Idec.Dr. Havrdova has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Biogen, Celgene Corporation, Merck, Novartis, Roche, Sanofi, and Teva. Dr. Havrdova has received research support from Czech Ministry of Education, project PROGRES Q27/LF1.Dr. Izquierdo Ayuso has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer, Biogen-Idec, Novartis, Sanofi, Merck-Serono, Almirall, Roche, Actelion, Celgene, and Teva.Dr. Eichau Madueno has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, Roche, and Teva. Dr. Lugaresi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory board member (Bayer, Biogen, Merck, Novartis, Roche, Sanofi, and Teva) and speaker honoraria, travel expenses (Bayer, Biogen, Merck, Novartis, Sanofi, Teva, and Fondazione Italiana Sclerosi Multipla).. Dr. Lugaresi has received research support from Research grants (Bayer, Biogen, Merck, Novartis, Sanofi, Teva, and Fondazione Italiana Sclerosi Multipla).. Dr. Hupperts has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Merck, Novartis, Sanofi, and Teva. Dr. Hupperts has received research support from Biogen, Merck, Novartis, Sanofi, and Teva.Dr. Sola has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with honoraria as a speaker or advisory board member from Bayer Schering, Biogen, Genzyme, Teva. Dr. Sola has received research support from Bayer Schering, Biogen, Genzyme, Merck Serono, Novartis, Sanofi, Teva. Dr. Ferraro has nothing to disclose. Dr. Butzkueven has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Institution (Monash University) received compensation for consulting, talks, advisory/steering board activities from Alfred Health, Biogen, Genzyme, Merck, Novartis. Dr. Butzkueven has received research support from Research support from Biogen, Merck, MS Research Australia, National Health and Medical Research (Australia), Novartis, Oxford Health Policy Forum, Pennycook Foundation, Roche. Dr. Grand-Maison has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi, and ONO Pharmaceuticals.Dr. Prat has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Received honoraria and operating grants from most pharmaceutical companies. Dr. Prat has received royalty, license fees, or contractual rights payments from Elan and Prothena.. Dr. Prat has received research support from Roche, Biogen and EMD Serono.. Dr. Girard has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Canada Innovation, Biogen, Novartis, Genzyme Sanofi, and EMD. Dr. Girard has received research support from Canadian Institutes of Health Research.Dr. Duquette has nothing to disclose. Dr. Petersen has received research support from Biogen Idec, Merck Serono, Novartis, Bayer Schering, Sanofi-Aventis, Roche, Genzyme. Dr. Grammond has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Novartis, Teva Neuroscience, Merck Serono, and the Canadian Multiple Sclerosis Society.Dr. Granella has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Novartis, Merck, Sanofi-Aventis, and Roche. Dr. Granella has received research support from Biogen and Sanofi Aventis. Dr. Van Pesch has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with My institution has received consultancy fees from Roche, Sanofi, Biogen, Merck, Novartis. Dr. Van Pesch has received research support from Research grants from Roche, Novartis and Sanofi.. Dr. Bergamaschi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer Schering, Biogen, Genzyme, Merck , Novartis, Sanofi-Aventis, Teva. Dr. Bergamaschi has received research support from Almirall, Bayer Schering, Biogen, Genzyme, Merck , Novartis, Sanofi-Aventis, Teva.. Dr. Kalincik has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with TK served on scientific advisory boards for Roche, Genzyme-Sanofi, Novartis, Merck, Celgene and Biogen, steering committee for Brain Atrophy Initiative by Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Bi. Dr. Kalincik has received personal compensation in an editorial capacity for TK has served on the editorial board of Multiple Sclerosis Journal, as an associate editor for BMC Neurology and reviewing editor for Frontiers in Neurology.. Dr. Kalincik has received research support from Biogen.