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Abstract Details

Antidrug Antibodies Have Minimal Impact on the Pharmacodynamic Profile and Clinical Efficacy of Alemtuzumab in RRMS Patients From the CARE-MS Studies
Multiple Sclerosis
P3 - Poster Session 3 (5:30 PM-6:30 PM)
15-078
To determine the effect of antidrug antibodies (ADAs) on the pharmacodynamics (PD)/efficacy of alemtuzumab in CARE-MS patients.
In the CARE-MS studies (NCT00530348; NCT00548405), 2 courses of alemtuzumab (12 mg/day; baseline: 5 days; 12 months later: 3 days) significantly improved clinical/MRI outcomes versus SC IFNB-1a over 2 years in RRMS patients. Efficacy was maintained in 2 consecutive extensions (NCT00930553; NCT02255656 [TOPAZ; ongoing]), wherein patients could receive additional alemtuzumab courses.
Alemtuzumab-binding ADA status (ever positive/always negative) was evaluated after Course (C) 2 and after additional alemtuzumab courses (C3 and C4, if received). PD/efficacy outcomes were assessed across various ADA titer thresholds.
712/811 (87.8%) patients from the pooled CARE-MS studies were ever positive for alemtuzumab-binding ADA, including 292/323 (90.4%) and 104/118 (88.1%) patients receiving C3 and C4, respectively. Median ADA titers peaked 1 month after each treatment course and decreased >60-fold 12 months later. No difference was observed in total lymphocyte or CD4+ T-cell depletion/repopulation patterns after C2 between ADA-positive or -negative patients; no ADA effect was observed on CD4+ T-cell depletion after C3. Findings in the CD4+ T-cell subset are representative of all major lymphocyte subsets. A year after C3, there were no significant differences between ADA-positive and -negative patients in annualized relapse rate (risk ratio [95% CI]: 0.94 [0.53–1.67]), percent relapse-free (odds ratio [95% CI]: 1.08 [0.56–2.06]), and mean change in EDSS scores (difference: 0.05; P=0.6902). Similar results were observed a year after C4. Across various titer thresholds, there was no consistent trend for an ADA effect with increasing titers.
Although the incidence of ADAs was high, it had minimal impact on long-term PD/efficacy after Course 2 or after additional courses (C3 and C4). These data indicate that ADAs do not limit the use of additional alemtuzumab courses to control disease activity when necessary.
Authors/Disclosures
Tjalf Ziemssen, MD, FAAN (University Clinic Dresden)
PRESENTER 		Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS . Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Roche. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sanofi. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for TEVA. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for Dresden Internation University. The institution of Dr. Ziemssen has received research support from Novartis. The institution of Dr. Ziemssen has received research support from Merck. The institution of Dr. Ziemssen has received research support from Sanofi. The institution of Dr. Ziemssen has received research support from BMS. The institution of Dr. Ziemssen has received research support from Roche.
Antonio Bertolotto, MD, FAAN (Ospedale Koelliker) Dr. Bertolotto has nothing to disclose.
Samuel F. Hunter, MD, PhD (Advanced Neurosciences Institute) The institution of Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbview. The institution of Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMDSerono. The institution of Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. The institution of Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. The institution of Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Osmotica. Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Janssen. Dr. Hunter has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Hunter has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMDSerono. Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Genentech. Dr. Hunter has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Novartis. Dr. Hunter has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Sanofi. The institution of Dr. Hunter has received research support from Biogen. The institution of Dr. Hunter has received research support from Abbvie. The institution of Dr. Hunter has received research support from Genentech/Roche. The institution of Dr. Hunter has received research support from Janssen. The institution of Dr. Hunter has received research support from Novartis. The institution of Dr. Hunter has received research support from Osmotica. The institution of Dr. Hunter has received research support from Sanofi. Dr. Hunter has received intellectual property interests from a discovery or technology relating to health care. Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving as a Speaker with MS Views and News. Dr. Hunter has a non-compensated relationship as a CEO - Volunteer with NeuroNexes/Novel Pharmaceutics Institute that is relevant to AAN interests or activities. Dr. Hunter has a non-compensated relationship as a Writing support with Novartis Pharmaceuticals that is relevant to AAN interests or activities. Dr. Hunter has a non-compensated relationship as a Writing Support with Osmotica that is relevant to AAN interests or activities. Dr. Hunter has a non-compensated relationship as a Writing support with Mallinckrodt that is relevant to AAN interests or activities. Dr. Hunter has a non-compensated relationship as a Writing Support with Sanofi that is relevant to AAN interests or activities.
Jan N. Lycke, MD Dr. Lycke 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. Lycke 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. Lycke has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS. Dr. Lycke 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. Lycke has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dr. Lycke 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. Lycke 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. Lycke 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. Dr. Lycke has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GeNeuro. The institution of Dr. Lycke has received research support from Sanofi.
Alan K. Jacobs, MD, FAAN (Satellos Biosciences) Dr. Jacobs has received personal compensation for serving as an employee of Immunovant, Inc. Dr. Jacobs has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Galler Consulting.
Luke Chung (Sanofi Genzyme) Luke Chung has received personal compensation for serving as an employee of Sanofi Genzyme. Luke Chung has received stock or an ownership interest from Sanofi Genzyme.
Qifeng Yu, PhD No disclosure on file
Isabel Firmino, MD (ALEXION AstraZeneca Rare Disease) No disclosure on file
Christopher C. LaGanke, MD (North Central Neurology Associates, PC) Dr. LaGanke 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. LaGanke 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. Dr. LaGanke has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. LaGanke has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sanofi. Dr. LaGanke has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Novartis. Dr. LaGanke has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for GSK. Dr. LaGanke has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Serono EMD. Dr. LaGanke has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Genentech. Dr. LaGanke has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Bristol Myers Squibb. Dr. LaGanke has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for TG Therapeutics.