Abstract Details

Title Indirect Treatment Comparison of Ravulizumab Versus Approved Treatment Options for Adults with Aquaporin-4 Immunoglobulin G-Positive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD)

Topic Autoimmune Neurology

Presentation(s) P10 - Poster Session 10 (11:45 AM-12:45 PM)

Poster/Presentation
Number 14-005

Objective To estimate relative treatment effects between ravulizumab and approved treatments (eculizumab, inebilizumab, and satralizumab) in adult patients with AQP4-IgG+ NMOSD.

Background NMOSD is an autoimmune disease that attacks the central nervous system. Considering several approved treatment options, a comparison of the relative treatment effects would facilitate selection of treatments for individual patients.

Design/Methods Based on the reported trial-specific results as identified from a systematic literature review, we estimated relative treatment effects between all competing interventions with network meta-analysis (NMA) techniques. The evidence base consisted of randomized controlled trials for all interventions except ravulizumab, which was evaluated in an external placebo-controlled trial. The endpoints of interest were time to first relapse (TTFR) and annualized relapse rate (ARR) with relative treatment effect measures obtained by the NMA expressed as hazard ratios (HR) and rate ratios (RR), respectively. Comparisons of the interventions were performed as monotherapy or in combination with immunosuppressants (ISTs). All analyses were performed in a Bayesian framework.

Results As monotherapy, ravulizumab was associated with a more than 90% reduction in experiencing a first relapse relative to satralizumab (HR [95% credible interval (Crl)], 0.08 [0.01-0.55]) and inebilizumab (0.09 [0.02-0.57]). TTFR was comparable between ravulizumab and eculizumab (0.86 [0.16-4.52]). Findings for ARR were consistent with TTFR; the rate of relapse with ravulizumab was 98% lower than with satralizumab (RR [95% Crl], 0.02 [0.00-0.42]) and inebilizumab (0.02 [0.00-0.38]) and was comparable to eculizumab. In combination with IST, ravulizumab showed an 85% reduction in first relapse relative to satralizumab (HR [95% Crl], 0.15 [0.03-0.78]).

Conclusions Ravulizumab is more efficacious at preventing relapse than satralizumab and inebilizumab and comparable with eculizumab among adults with AQP4-IgG+ NMOSD when used as monotherapy. In combination with IST, ravulizumab was more efficacious than satralizumab and comparable to eculizumab.

Authors/Disclosures
Stacey Clardy, MD, PhD, FAAN (University of Utah) PRESENTER	Dr. Clardy has received personal compensation for serving as an employee of Veterans Health Administration (VHA). Dr. Clardy has received personal compensation for serving as an employee of University of Utah Health. Dr. Clardy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AstraZeneca/Alexion. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen/Horizon. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arialys. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kyverna. Dr. Clardy 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 Neurology/AAN Publications. The institution of Dr. Clardy has received research support from NIH/NINDS. The institution of Dr. Clardy has received research support from SRNA. The institution of Dr. Clardy has received research support from Alexion/AstraZeneca. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a AAN Summer Meeting CoDirector Travel and Lodging with AAN. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Grand Rounds Travel/Lodging/Honoraria with U of Iowa, Miami, Stanford, Barrow, Beaumont Health, CCF, Emory, Penn State, Mayo Clinic, Walter Reed.
Sean J. Pittock, MD, FAAN (Mayo Clinic Dept of Neurology)	Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys. The institution of 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 Alexion. The institution of 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. The institution of 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 Roche/Genentech. The institution of Dr. Pittock has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion/AstraZeneka. The institution of Dr. Pittock has received research support from NIH. 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. Pittock has received publishing royalties from a publication relating to health care.
Orhan Aktas, MD (Neurologische Klinik)	Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen/Horizon. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubish Tanake. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AstraZeneca. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen/Horizon. The institution of Dr. Aktas has received research support from German Research Foundation. The institution of Dr. Aktas has received research support from German Ministry of Science. The institution of Dr. Aktas has received research support from Neuromyelitis optica Study Group (NEMOS).
Jin Nakahara, MD, PhD, FAAN (Keio University School of Medicine)	Prof. Nakahara 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. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Mitsubishi-Tanabe. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Chugai. Prof. Nakahara has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Novartis. Prof. Nakahara has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Prof. Nakahara has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Prof. Nakahara has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Chugai. Prof. Nakahara has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Mitsubishi-Tanabe. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for The Japanese Society for Internal Medicine. The institution of Prof. Nakahara has received research support from Chugai. The institution of Prof. Nakahara has received research support from Japan Society for the Promotion of Science.
Noriko Isobe, MD (Department of Neurology, Kyushu University)	Dr. Isobe has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alexion Pharma. Dr. Isobe has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Chugai Pharma . Dr. Isobe has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Mitsubishi Tanabe. Dr. Isobe has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Novartis Pharma. Dr. Isobe has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Isobe has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda Pharmaceutical. Dr. Isobe has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Daiichisankyo. Dr. Isobe has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Argenx. The institution of Dr. Isobe has received research support from Chugai Pharmaceutical. The institution of Dr. Isobe has received research support from Kyowa Kirin. The institution of Dr. Isobe has received research support from CSL Behring. The institution of Dr. Isobe has received research support from Boehringer Ingelheim. The institution of Dr. Isobe has received research support from Otsuka Pharma. The institution of Dr. Isobe has received research support from Sumitomo Pharmaceutical . The institution of Dr. Isobe has received research support from Eisai.
Diego Centonze	Diego Centonze has nothing to disclose.
Sami Fam	Sami Fam has received personal compensation for serving as an employee of Alexion Pharmaceuticals. Sami Fam has or had stock in Astra Zeneca.
Adrian Kielhorn	Adrian Kielhorn has received personal compensation for serving as an employee of Alexion. Adrian Kielhorn has stock in Alexion.
Jeffrey Yu, PhD (Alexion)	Dr. Yu has received personal compensation for serving as an employee of Alexion. Dr. Yu has stock in AstraZeneca.
Jeroen Jansen	No disclosure on file
Ina Zhang (PRECISIONheor)	No disclosure on file

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