Abstract Details

Title 10 Years of Ocrelizumab Treatment in Multiple Sclerosis: Long-term Efficacy and Safety Clinical Trial Data

Topic Multiple Sclerosis

Presentation(s) S31 - Multiple Sclerosis: Therapeutics and Clinical Decision Making (1:48 PM-2:00 PM)

Poster/Presentation
Number 005

Background

OCR is a highly effective therapy approved for treatment of RMS and PPMS. Understanding the long-term efficacy and safety of OCR is critical considering the longer treatment durations associated with MS.

Objective

To assess the long-term efficacy and safety of ocrelizumab (OCR) in patients with relapsing and primary progressive multiple sclerosis (pwRMS/pwPPMS).

Design/Methods

Patients randomized to receive OCR or comparator (interferon [IFN] β-1a in OPERA I/II [NCT01247324/NCT01412333]; placebo [PBO] in ORATORIO [NCT01194570]) either continued OCR (OCR-OCR) or switched from comparator to OCR (IFN-OCR; PBO-OCR) on entering the open-label extension studies. Disability accumulation (time to 48-week confirmed disability progression [48W-CDP] on Expanded Disability Status Scale [EDSS] and composite CDP [cCDP; 48W-CDP-EDSS, or ≥20% increases in Timed 25-Foot Walk or Nine-Hole Peg Test]) was analyzed up to Week 528. Safety outcomes were reported as rates per 100 patient years.

Results

After 10 years, over three-quarters (76.6%) of pwRMS on OCR-OCR were free from 48W-CDP-EDSS events and 91.9% did not need a walking aid; risk of reaching either was significantly lower in pwRMS initiating OCR earlier versus delayed treatment (HR, CI: 0.77, 0.61–0.96; p=0.0183; 0.58, 0.41–0.84; p=0.003). In pwPPMS on OCR-OCR, after 10 years, 36.4% and 18.6% were free from 48W-CDP-EDSS and 48W-cCDP events, respectively, while most (80.4%) did not need a wheelchair; risk of reaching each was lower in pwPPMS initiating OCR earlier versus delayed treatment (HR, CI: 0.74, 0.61–0.91; p=0.0041; 0.78, 0.65–0.93; p=0.0064; 0.70, 0.48–1.03; p=0.0708). Over 10 years, (serious) adverse event rates were consistent with the controlled treatment period, treatment withdrawal was infrequent and malignancy rates remained within epidemiologic background. Serious infection rates were low and stable in both pwRMS and pwPPMS, irrespective of immunoglobulin G levels.

Conclusions

Earlier treatment with ocrelizumab resulted in greater reductions in disability progression, with a favorable long-term safety profile in pwRMS and pwPPMS.

Authors/Disclosures
Stephen L. Hauser, MD (UCSF Weill Institute for Neurosciences) PRESENTER	Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NGM Bio. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BD. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pheno Therapeutics. Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Accure. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alector. Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Annexon. Dr. Hauser 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 Neurona. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Roche that is relevant to AAN interests or activities. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Novartis that is relevant to AAN interests or activities.
Ludwig Kappos, MD, FAAN (RC2NB, University Hospital Basel)	The institution of Dr. Kappos has received research support from Bayer. The institution of Dr. Kappos has received research support from Biogen. The institution of Dr. Kappos has received research support from Genentech. The institution of Dr. Kappos has received research support from Genzyme. The institution of Dr. Kappos has received research support from Janssen. The institution of Dr. Kappos has received research support from Merck Serono. The institution of Dr. Kappos has received research support from Minoryx. The institution of Dr. Kappos has received research support from Novartis. The institution of Dr. Kappos has received research support from Roche. The institution of Dr. Kappos has received research support from Sanofi. The institution of Dr. Kappos has received research support from Santhera. The institution of Dr. Kappos has received research support from Swiss MS Society, Swiss National Research Foundation, European Union, Roche Research Foundation, Innosuisse. The institution of Dr. Kappos has received research support from Shionogi. The institution of Dr. Kappos has received research support from Japan Tobacco. The institution of Dr. Kappos has received research support from Auriga Vision AG. The institution of Dr. Kappos has received research support from EMD Serono. The institution of Dr. Kappos has received research support from Glaxo Smith Kline. The institution of Dr. Kappos has received research support from Wellmera AG. The institution of Dr. Kappos has received research support from Eli Lilly (Suisse) SA. The institution of Dr. Kappos has received research support from Bristol Myers Squibb. The institution of Dr. Kappos has received research support from Celltrion Inc. Dr. Kappos has received intellectual property interests from a discovery or technology relating to health care.
Massimo Filippi, MD, FAAN (Ospedale San Raffaele, Neuroimaging Research Unit)	Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi;. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi- Genzyme, Takeda. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.
Jerry S. Wolinsky, MD, FAAN (McGovern Medical School, UTHealth)	Dr. Wolinsky has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avotres. Dr. Wolinsky has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Brainstorm Cell Therapeutics. Dr. Wolinsky has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cleveland Clinic Foundation. Dr. Wolinsky has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Wolinsky has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Inmagene. Dr. Wolinsky has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis/Sandoz. Dr. Wolinsky has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Wolinsky has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. Dr. Wolinsky has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for University of Alabama Birmingham. Dr. Wolinsky has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Wolinsky has received intellectual property interests from a discovery or technology relating to health care. Dr. Wolinsky has received intellectual property interests from a discovery or technology relating to health care.
Martin Weber, MD (Universitätsmedizin Göttingen)	Dr. Weber has nothing to disclose.
Jacqueline A. Nicholas, MD (OhioHealth Riverside Methodist Hospital)	Dr. Nicholas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Nicholas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Nicholas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Nicholas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squib. Dr. Nicholas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Nicholas 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. Nicholas has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Greenwich Biosciences. Dr. Nicholas 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. Dr. Nicholas has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Nicholas has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for EMD Serono. Dr. Nicholas has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Genentech. Dr. Nicholas has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Nicholas has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Vielo Bio. Dr. Nicholas has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb. The institution of Dr. Nicholas has received research support from Novartis. The institution of Dr. Nicholas has received research support from Biogen. The institution of Dr. Nicholas has received research support from Genentech. The institution of Dr. Nicholas has received research support from PCORI. Dr. Nicholas has a non-compensated relationship as a Physician with National MS Society that is relevant to AAN interests or activities. Dr. Nicholas has a non-compensated relationship as a Physician with Siegal Rare Neuroimmune Association that is relevant to AAN interests or activities.
Cathy Chognot	No disclosure on file
Hans-Martin Schneble, MD (Roche)	Dr. Schneble has received personal compensation for serving as an employee of F. Hoffmann-La Roche Ltd.. Dr. Schneble has received stock or an ownership interest from F. Hoffmann-La Roche, Ltd..
Qing Wang	Qing Wang has nothing to disclose.
Gavin Giovannoni, MD (QMUL)	Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck KGaA. Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Japanese Tobacco. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aurinia Pharmaceuticals. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Giovannoni 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. Giovannoni 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. Giovannoni 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. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Medscape. Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Oxford Health Policy Forum. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Peervoice. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Bristows .
Xavier Montalban, MD, PhD, FAAN (Vall Hebron University Hospital-Multiple Sclerosis Centre of Catalonia)	The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck/ EMD Serono. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Hoffmann-La Roche. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Actelion/ Janssen. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for BMS/ Celgene. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi/ Genzyme. Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Actelion/ Janssen. Dr. Montalban 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. Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS/ Celgene. Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/ EMD Serono. Dr. Montalban 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. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffmann-La Roche. Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyme. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic Therapeutics. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viatris/ Mylan. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sandoz. The institution of Dr. Montalban has received research support from Biogen. The institution of Dr. Montalban has received research support from Hoffmann-La Roche. The institution of Dr. Montalban has received research support from Sanofi/ Genzyme. The institution of Dr. Montalban has received research support from Merck/ EMD Serono. The institution of Dr. Montalban has received research support from Novartis. The institution of Dr. Montalban has received research support from Teva Pharmaceuticals. The institution of Dr. Montalban has received research support from Actelion/ Janssen. The institution of Dr. Montalban has received research support from BMS/ Celgene.