Abstract Details

Title Infusion-Related Reactions With Ocrelizumab: Risk Factors, Symptom Management and Patient Choices in the ENSEMBLE PLUS Study

Topic Multiple Sclerosis

Presentation(s) P7 - Poster Session 7 (8:00 AM-9:00 AM)

Poster/Presentation
Number 3-003

Objective

To assess patient preference for conventional (CON) or shorter (SHORT) infusion post unblinding of the ENSEMBLE PLUS study.

Background

Shortening the infusion duration of ocrelizumab to 2 hours reduces total site stay. Previous infusion-related reactions (IRRs) are a risk factor for future IRRs. Identification of specific symptoms, potential risk factors during infusions, was investigated in ENSEMBLE PLUS.

Design/Methods

ENSEMBLE PLUS was a randomized, double-blind substudy to ENSEMBLE (NCT03085810). Ocrelizumab (600 mg) administered over the approved 3.5-hour infusion time (CON) was compared with a 2-hour infusion (SHORT). The primary endpoint was the proportion of patients with IRRs at first randomized dose (RD). Risk factors were assessed for development of IRRs. Patients could switch between CON/SHORT infusion post unblinding.

Results Within 24 hours of first RD, 27.1% (CON: n=101/373) versus 28.8% (SHORT: n=107/372) of patients had IRRs. Most IRRs (CON 100%; SHORT 97.2%) were mild or moderate (Grade 1 or 2);none were Grade 4 or 5 IRRs. No IRR-related discontinuations occurred. The proportion of patients with throat irritation as an IRR symptom was 23.1% (CON) and 33.0% (SHORT) in patients with ≥1 throat irritation before first RD; in patients with no throat irritation before first RD, the proportion was 5.3% (CON) and 5.4% (SHORT). Patient migraine/headache history did not correlate with IRR development. Post unblinding, 79.7% patients switched to SHORT infusion from CON, and 94.6% patients stayed on SHORT infusion. Treating neurologists frequently attempted minor adaptations of pre-medication timing/regimen without substantially affecting IRR incidence.

Conclusions

Previous IRRs may be a risk factor for future IRRs but are not influenced by shorter infusion time. Pre-randomization throat irritation was predictive of developing throat irritation as an IRR symptom, however migraines were not. Most patients remained on/moved to SHORT infusion after unblinding. Overall, IRRs did not strongly influence patient decisions. Most pre-medication changes had no impact on IRR incidence.

Authors/Disclosures
Robert A. Bermel, MD, FAAN (Cleveland Clinic) PRESENTER	Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi/Genzyme. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech/Roche. Dr. Bermel has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Bermel has received research support from Biogen. The institution of Dr. Bermel has received research support from Roche. The institution of Dr. Bermel has received research support from Novartis. Dr. Bermel has received intellectual property interests from a discovery or technology relating to health care.
Joep Killestein (Amsterdam UMC)	Joep Killestein has nothing to disclose.
Thomas A. Berger, MD (Dept. of Neurology, Medical University of Vienna)	Prof. Berger has received personal compensation in the range of $10,000-$49,999 for serving as a speaker at scientific meetings and participant of local and international advisory boards with various companies producing and markerting treatments for multiple sclerosis (Almirall, Biogen, Biologix, Bionorica, Celgene-BMS, Merck, Novartis, Roche, Sanofi-Genzyme, TG Therapeutics, UCB).
Bruno Brochet, MD, FEAN (University of Bordeaux)	Prof. Brochet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Prof. Brochet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for celgene. Prof. Brochet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for jansen. Prof. Brochet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for biogen. Prof. Brochet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for novartis. Prof. Brochet has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for merck. Prof. Brochet has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for biogen. Prof. Brochet has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for celgene.
William M. Carroll, MD, MBBS, FRACP, FAAN (SJOG Neurology)	Dr. Carroll has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Carroll has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Carroll has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck.
Mark S. Freedman, MD, FAAN (University of Ottawa)	Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Actelion(Janssen/J&J). Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BiogenIdec. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS/Celgene. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Inc. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Actelion (Janssen/J&J). Dr. Freedman 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. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Atara Biotherapeutics. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer Healthcare. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for BiogenIdec. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Clene Nanomedicine. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GRI Bio. Dr. Freedman 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. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Magenta Therapeutics. Dr. Freedman 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. Dr. Freedman 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. Freedman 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. Dr. Freedman has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi Genzyme. Dr. Freedman has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. The institution of Dr. Freedman has received research support from Sanofi Genzyme.
Trygve Holmoy, MD (Aventis Pharma AS)	Dr. Holmoy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Norwegian MS Society. Dr. Holmoy has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Holmoy has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Holmoy has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Holmoy has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Holmoy has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck.
Rana Karabudak, MD (Academic Neurologist)	Dr. Karabudak has nothing to disclose.
Carlos Nos, MD	Dr. Nos has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for F. Hoffmann-La Roche Ltd..
Francesco Patti, MD	Dr. Patti has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. The institution of Dr. Patti has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Almirall. Dr. Patti has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Meyers. Dr. Patti has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Johnson and Johnson. The institution of Dr. Patti has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck. The institution of Dr. Patti has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Patti has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. The institution of Dr. Patti has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Patti has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Almirall, Bayer, Biogen, Bristol Meyers and Squibb Merck, Roche, Sanofi, TEVA. Dr. Patti has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for University of Catania and AISM/FISM, Fondazione Italiana Sclerosi Multipla. Dr. Patti has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers in Neurology.
Amy P. Perrin Ross, RN, APN MSN, CNRN (Loyola University Medical Center)	Ms. Perrin Ross has received personal compensation in the range of $0-$499 for serving as a Consultant for Horizon. Ms. Perrin Ross has received personal compensation in the range of $0-$499 for serving as a Consultant for EMD Serono. Ms. Perrin Ross has received personal compensation in the range of $0-$499 for serving as a Consultant for Alexion. Ms. Perrin Ross has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Ms. Perrin Ross has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis.
Ludo J. Vanopdenbosch, MD, FAAN (Dr Ludo Vanopdenbosch BVBA)	Dr. Vanopdenbosch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for celgene. Dr. Vanopdenbosch 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. Vanopdenbosch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for F Hoffmann La Roche. Dr. Vanopdenbosch 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. Vanopdenbosch 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. Dr. Vanopdenbosch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme.
Timothy L. Vollmer, MD, FAAN	The institution of Dr. Vollmer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen IDEC. The institution of Dr. Vollmer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech/Roche. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Siranax. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Meyers Squib. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viela Bios. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. The institution of Dr. Vollmer has received research support from Rocky Mountain MS Center. The institution of Dr. Vollmer has received research support from Biogen. The institution of Dr. Vollmer has received research support from Actelion. The institution of Dr. Vollmer has received research support from Genentech/Roche. The institution of Dr. Vollmer has received research support from Anokion. The institution of Dr. Vollmer has received research support from TG Therapeutics.
Regine Buffels, MD	Dr. Buffels has nothing to disclose.
Karen Kadner	No disclosure on file
Oscar Bortolami (Roche ExBP)	No disclosure on file
Hans-Peter Hartung, MD, FAAN (Heinrich Heine University Medical Faculty)	Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS Celgene. Dr. Hartung has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Geneuro. Dr. Hartung 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. Dr. Hartung 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. Hartung 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. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Hartung 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. Hartung has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers Neurology.

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