Abstract Details

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

Topic Multiple Sclerosis

Presentation(s) S29 - Multiple Sclerosis: Disease-modifying Therapy (2:00 PM-2:12 PM)

Poster/Presentation
Number 006

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<0.001). This difference remained clinically (>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.

Authors/Disclosures
Anna He, MBBS (Centre for Neuroscience, Karolinska Institute) PRESENTER	Dr. He has nothing to disclose.
	No disclosure on file
J William L. Brown, MD (University of Cambridge)	Dr. Brown has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Brown has received publishing royalties from a publication relating to health care.
Lana Zhovtis Ryerson, MD (Jersey Shore University Medical Center)	Dr. Zhovtis Ryerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Zhovtis Ryerson has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi.
Ilya Kister, MD, FAAN (NYU School of Medicine)	Dr. Kister has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech-Roche. Dr. Kister has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. The institution of Dr. Kister has received research support from Genentech. The institution of Dr. Kister has received research support from Novartis. Dr. Kister has received publishing royalties from a publication relating to health care.
	No disclosure on file
	No disclosure on file
Eva Havrdova, MD (Neurologicka Klinika 1 LF UK)	Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi.
Guillermo Izquierdo Ayuso, MD (Servicio De Neurologia)	Dr. Izquierdo Ayuso has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer, Biogen Idec, Novartis, Sanofi, Merck Serono, Roche, Actelion and Celgene. Dr. Izquierdo Ayuso has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme, Novartis, Sanofi Aventis, Alexion.
Sara Eichau Madueno	Sara Eichau Madueno has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Sara Eichau Madueno has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Sara Eichau Madueno has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Sara Eichau Madueno has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Sara Eichau Madueno has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Sara Eichau Madueno has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Novartis. Sara Eichau Madueno has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Sara Eichau Madueno has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sanofi. Sara Eichau Madueno has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Merck.
Alessandra Lugaresi, MD (Istituto delle Scienze Neurologiche di Bologna)	Dr. Lugaresi has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck Serono. Dr. Lugaresi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis Pharma. Dr. Lugaresi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Lugaresi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Lugaresi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Lugaresi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Lugaresi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mylan. Dr. Lugaresi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Sqibb. Dr. Lugaresi has a non-compensated relationship as a Speaker at meetings, participant in trials with Fondazione Italiana Sclerosi Multipla that is relevant to AAN interests or activities.
R.M.M. Hupperts, MD (Biogen Int. B.V.)	No disclosure on file
Patrizia Sola (Nuovo Ospedale Civile S. Agostino-Estense)	Patrizia Sola has nothing to disclose.
Diana Ferraro, MD, PhD (University of Modena and Reggio Emilia)	Dr. Ferraro has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme. Dr. Ferraro has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Ferraro has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Ferraro has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Ferraro has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for TEVA. Dr. Ferraro has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Binding Site. Dr. Ferraro has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck.
Helmut Butzkueven, MD, MBBS (Alfred Hospital)	Dr. Butzkueven has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Oxford Health Policy Forum. The institution of Dr. Butzkueven has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. The institution of Dr. Butzkueven has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck. The institution of Dr. Butzkueven has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. The institution of Dr. Butzkueven has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Butzkueven has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for MSBase . The institution of Dr. Butzkueven has received research support from NHMRC. The institution of Dr. Butzkueven has received research support from Biogen. The institution of Dr. Butzkueven has received research support from Roche. The institution of Dr. Butzkueven has received research support from Novartis.
Francois Grand-Maison, MD (Francois Grand'Maison MD INC)	Dr. Grand-Maison has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Grand-Maison has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Grand-Maison has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Serono. Dr. Grand-Maison has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Grand-Maison has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis .
Alexandre Prat, MD (CHUM Hopital Norte Dame/ Dept of Neurology)	The institution of Dr. Prat has received research support from CIHR and MSSC.
J M. Girard, MD	Dr. Girard has nothing to disclose.
Pierre Duquette, MD	The institution of Dr. Duquette has received research support from Biogen and Genzyme.
Thor Petersen (Arhus Sygehus)	No disclosure on file
Pierre Grammond, MD (Hotel-Dieu De Levis Hospital)	Dr. Grammond has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Grammond has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Grammond has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Grammond has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pendopharm. Dr. Grammond has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Grammond has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Grammond has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Serono. The institution of Dr. Grammond has received research support from Roche.
Franco Granella (Zeneca-UK)	Franco Granella has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Franco Granella has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Franco Granella has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck Serono.
Vincent Van Pesch, MD, PhD (Cliniques Universitaires Saint-Luc)	Vincent Van Pesch, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Vincent Van Pesch, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Vincent Van Pesch, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Vincent Van Pesch, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Vincent Van Pesch, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene. Vincent Van Pesch, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. The institution of Vincent Van Pesch, MD, PhD has received research support from Biogen.
Roberto Bergamaschi	Roberto Bergamaschi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Roberto Bergamaschi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Roberto Bergamaschi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Roberto Bergamaschi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Roberto Bergamaschi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Roberto Bergamaschi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Roberto Bergamaschi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi.
Tomas Kalincik	Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi Genzyme. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Tomas Kalincik has received personal compensation in the range of $500-$4,999 for serving as a Consultant for National Health and Medical Research Council. Tomas Kalincik has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MS Research Australia. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Tomas Kalincik has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Tomas Kalincik has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for WebMD Global. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Novartis. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sanofi Genzyme. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Teva. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for BioCSL. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Merck. Tomas Kalincik has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. The institution of Tomas Kalincik has received research support from Biogen. The institution of Tomas Kalincik has received research support from Novartis. The institution of Tomas Kalincik has received research support from Genzyme. The institution of Tomas Kalincik has received research support from Roche. The institution of Tomas Kalincik has received research support from Celgene. The institution of Tomas Kalincik has received research support from Merck. The institution of Tomas Kalincik has received research support from MSBase Foundation. The institution of Tomas Kalincik has received research support from ARSEP and EDMUS Foundations. The institution of Tomas Kalincik has received research support from MS Research Australia. The institution of Tomas Kalincik has received research support from National Health and Medical Research Council. The institution of Tomas Kalincik has received research support from Australian Research Council. The institution of Tomas Kalincik has received research support from MS Society. The institution of Tomas Kalincik has received research support from Trish Foundation. Tomas Kalincik has a non-compensated relationship as a scientific leadership group vice-chair with MSBase Foundation that is relevant to AAN interests or activities.

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