Long-term efficacy and safety of eculizumab monotherapy in AQP4+ neuromyelitis optica spectrum disorder (1578)

Objective: To examine the long-term efficacy and safety of eculizumab monotherapy in patients with aquaporin-4 immunoglobulin G-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) during PREVENT and/or its ongoing open-label extension (OLE).

Background: In PREVENT, eculizumab was well tolerated and significantly reduced relapse risk versus placebo in patients with AQP4+ NMOSD with or without concomitant immunosuppressive therapy (IST).

Design/Methods: During PREVENT (NCT01892345) and its OLE (NCT02003144), adults with AQP4+ NMOSD received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (PREVENT only) with or without concomitant IST. Relapses, hospitalizations, IST changes and adverse events (AEs) with eculizumab monotherapy (PREVENT and its OLE; interim data cut-off, July 31, 2019) or with placebo alone (PREVENT) were descriptively analyzed post hoc.

Results: During PREVENT and/or its OLE, 33 patients received eculizumab monotherapy for 85.3 patient-years (PY). Adjudicated relapses occurred in 1/33 patients (annualized relapse rate, 0.012; 95% confidence interval [CI]: 0.002–0.082) versus 7/13 with placebo alone in PREVENT. At 192 weeks, 96.2% of patients receiving eculizumab monotherapy were relapse-free (95% CI: 0.757–0.994) versus 93.8% of patients receiving eculizumab with concomitant IST (95% CI: 0.867–0.972). No patients receiving eculizumab monotherapy required hospitalization for a relapse and none started an IST. The treatment-related AE rate with eculizumab monotherapy in PREVENT and/or its OLE was similar to that with placebo alone in PREVENT (181.0 versus 186.0 events/100 PY), the infection rate was similar between these groups (174.1 versus 186.0 events/100 PY), and the treatment-related serious AE rate was lower with eculizumab monotherapy than with placebo alone (5.7 versus 23.3 events/100 PY). No meningococcal infections or deaths occurred among these patients.

Conclusions: A very high proportion of patients who had experienced 1–2 relapses in the pre-study year remained relapse-free through 192 weeks of eculizumab monotherapy. Long-term eculizumab monotherapy was well tolerated and effective in reducing relapse risk in AQP4+ NMOSD.

Disclosure: Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech, Inc.. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage Therapeutics, Inc.. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB, Inc. Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffman/LaRoche AG. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genetech. The institution of Dr. Pittock has received research support from Grifols. The institution of Dr. Pittock has received research support from NIH. The institution of Dr. Pittock has received research support from Viela Bio/MedImmune. The institution of Dr. Pittock has received research support from Alexion Pharmaceuticals. The institution of Dr. Pittock has received research support from Alexion Pharmaceuticals. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Fujihara 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. Fujihara has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tanabe-Mitsubishi. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Chigai. Dr. Fujihara has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for EMC. The institution of Dr. Fujihara has received research support from Ministry of Education, Science and Technology of Japan. The institution of Dr. Fujihara has received research support from Ministry of Health, Welfare and Labor of Japan. Dr. Fujihara has received personal compensation in the range of $10,000-$49,999 for serving as a speaker, chair, etc with Novartis. Dr. Fujihara has received personal compensation in the range of $5,000-$9,999 for serving as a speaker, chair, etc with Biogen. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as a speaker, chair, etc with Tanabe-Mitsubishi. Dr. Fujihara has received personal compensation in the range of $5,000-$9,999 for serving as a apeaker, chair, etc with Chugai. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as a speaker, chair, etc with Alexion. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as a chair with Asahi Kasei Medical. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as a speaker with Eisai. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as a speaker, chair with Teijin. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as a speaker with Bayer. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as a speaker with Roche. Dr. Palace has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck, Mitsubushi, UCB, Roche, Amplo, Alexion, Vitaccess, Argenx. Dr. Palace 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, Roche, Argenx, Alexion. Dr. Palace has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Merck, Roche, Viela Bio, Alexion. The institution of Dr. Palace has received research support from Merck, MedImmune, MS Society, AMPLO. Achim Berthele, MD has nothing to disclose. Dr. Kim has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aprilbio, HanAll BioPharma, Viela Bio. Dr. Kim has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion, Biogen, Celltrion, Eisai, Merck Serono, Novartis, Sanofi Genzyme, Teva-Handok. Dr. Kim 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 Multiple Sclerosis Journal, Journal of Clinical Neurology. Celia Oreja Guevara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for merck. Celia Oreja Guevara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for roche. Celia Oreja Guevara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for sanofi. Celia Oreja Guevara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for novartis. Celia Oreja Guevara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for alexion. Dr. Nakashima 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. Nakashima 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. Nakashima 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. Nakashima has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Chugai. Dr. Nakashima has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alexion. Dr. Nakashima has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Nakashima has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Novartis. Dr. Nakashima has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Chugai. Dr. Nakashima has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Teijin. The institution of Dr. Nakashima has received research support from LSI Medience. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Pharma. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Pharma. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viela Bio. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Levy has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Various law firms. The institution of Dr. Levy has received research support from National Institutes Health. Shulian Shang has received personal compensation for serving as an employee of Alexion Pharmaceuticals. Shulian Shang has received stock or an ownership interest from Alexion Pharmaceuticals. Dr. Yountz has received personal compensation for serving as an employee of Alexion. Dr. Yountz has received stock or an ownership interest from Alexion. Larisa Miller, PharmD has received personal compensation for serving as an employee of Alexion Pharmaceuticals, Inc. Larisa Miller, PharmD has received stock or an ownership interest from Alexion Pharmaceutical, Inc. Dr. Armstrong has received personal compensation for serving as an employee of Alexion Pharmaceuticals Inc.. Dr. Armstrong has received stock or an ownership interest from Alexion Pharmaceuticals Inc.. Dr. Wingerchuk has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viela Bio. Dr. Wingerchuk has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MedImmune. Dr. Wingerchuk has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Wingerchuk 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. Dr. Wingerchuk 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. Wingerchuk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Third Rock Ventures. Dr. Wingerchuk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Reistone. Dr. Wingerchuk has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene. Dr. Wingerchuk 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. Wingerchuk 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. Wingerchuk has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wolters Kluwers. The institution of Dr. Wingerchuk has received research support from Alexion.