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Abstract Details

Serum Ig Levels and Risk of Serious Infections by Baseline Ig Quartile in the Pivotal Phase III Trials and Open-Label Extensions of Ocrelizumab in Multiple Sclerosis
Multiple Sclerosis
P6 - Poster Session 6 (12:00 PM-1:00 PM)
9-008

A reduction in serum Ig levels was observed over 6 years of ocrelizumab treatment, with Ig levels remaining above the lower limit of normal (LLN) for the majority of patients. An apparent association between decreased Ig levels and SIs was previously reported.

To characterize the temporal evolution of immunoglobulin (Ig) levels and the risk of serious infections (SIs) by baseline Ig quartile in the Phase III OPERA I (NCT01247324), OPERA II (NCT01412333) and ORATORIO (NCT01194570) trials of ocrelizumab in multiple sclerosis, and their open-label extensions.

Serum Ig levels were measured at least every 24 weeks. Baseline IgG, IgM and IgA quartiles (g/L) were determined for OPERA and ORATORIO; Q1 represents patients with lowest baseline levels. LLNs for IgG, IgM and IgA were defined as 5.65g/L, 0.40g/L and 0.70g/L, respectively. Periods of Ig<LLN and SI rates per baseline quartiles were assessed.

Over 6 years of treatment, mean change in IgG levels, g/L (% change) per year by baseline quartile were: Q1, –0.24 (–2.9%); Q2, –0.32 (–3.2%); Q3, –0.40 (–3.6%); Q4, –0.40 (–3.0%) in OPERA, and Q1, –0.23 (–2.9%); Q2, –0.28 (–2.9%); Q3, –0.35 (–3.1%); Q4, –0.51 (–3.8%) in ORATORIO. SI rates per 100 patient-years (95% CI) were: Q1, 1.63 (0.95–2.61); Q2, 1.55 (0.90–2.48); Q3, 1.51 (0.86–2.45); Q4, 1.11 (0.57–1.94) in OPERA, and Q1, 4.04 (2.66–5.87); Q2, 3.81 (2.46–5.62); Q3, 5.39 (3.76–7.50); Q4, 2.17 (1.22–3.59) in ORATORIO. Changes in IgM/IgA levels, and patient demographics and disease characteristics, for each quartile will also be presented.

Patients with lower baseline IgG levels demonstrated less absolute IgG decline versus patients with higher baseline IgG levels. A similar percentage decline was observed across quartiles. Overall, rates of SIs per baseline IgG quartiles were similar and remain low.

Authors/Disclosures
Amit Bar-Or, MD, FRCPC (University of Pennsylvania)
PRESENTER
Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen/Actelion. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Atara Biotherapeutics. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merk/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Bar-Or 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. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Bar-Or 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. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/EMD Serono. Dr. Bar-Or 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. The institution of Dr. Bar-Or has received research support from Novartis. The institution of Dr. Bar-Or has received research support from Biogen. The institution of Dr. Bar-Or has received research support from Roche/Genentech. The institution of Dr. Bar-Or has received research support from Merck/EMD Serono.
Robert A. Bermel, MD, FAAN (Cleveland Clinic) Dr. Bermel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. 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 $500-$4,999 for serving as a Consultant for Viela Bio. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 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 Merck Serono. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Astra Zeneca. Dr. Bermel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for LabCorp. 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.
Martin *Use 130037 Weber, MD (Neurologie & Neuropathologie, Uni Gottingen) Martin Weber, MD has nothing to disclose.
Richard W. Hughes, MBBS (Biogen) Dr. Hughes has received personal compensation for serving as an employee of Biogen. Dr. Hughes has stock in Biogen.
Chien-Ju Lin Chien-Ju Lin has nothing to disclose.
Jianmei Wang No disclosure on file
Annette Sauter, PhD (F. Hoffmann-La Roche Ltd) Dr. Sauter has received personal compensation for serving as an employee of F.Hoffmann-La Roche .
Harold Koendgen, MD Dr. Koendgen has received personal compensation for serving as an employee of F. Hoffmann-La Roche Ltd. Dr. Koendgen has received stock or an ownership interest from F. Hoffmann-La Roche Ltd .
Licinio Manuel Craveiro, MD, PhD (Roche) Dr. Craveiro has received personal compensation for serving as an employee of Hoffmann La-Roche. Dr. Craveiro has received stock or an ownership interest from Hoffmann La-Roche.
Stephen L. Hauser, MD (UCSF Weill Institute for Neurosciences) 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.
Tobias Derfuss An immediate family member of Tobias Derfuss has received personal compensation for serving as an employee of Novartis. The institution of Tobias Derfuss has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Tobias Derfuss has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. The institution of Tobias Derfuss has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. The institution of Tobias Derfuss has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. The institution of Tobias Derfuss has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. The institution of Tobias Derfuss has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GeNeuro. Tobias Derfuss has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MedDay. Tobias Derfuss has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Tobias Derfuss has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Actelion. Tobias Derfuss has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Merck. Tobias Derfuss has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Roche. An immediate family member of Tobias Derfuss has received stock or an ownership interest from Novartis. The institution of Tobias Derfuss has received research support from Roche. The institution of Tobias Derfuss has received research support from Biogen.