COMPARATIVE EFFICACY OF INEBILIZUMAB VERSUS RITUXIMAB FOR ATTACK PREVENTION IN AQUAPORIN-4 ANTIBODY-POSITIVE NEUROMYELITIS OPTICA SPECTRUM DISORDER: A MATCHING-ADJUSTED INDIRECT COMPARISON ANALYSIS
Author(s)
Bruce A. Cree, MD1, Jacqueline Palace, MD2, Kazuo Fujihara, MD3, Moushmi Singh, MSc4, Therese Aubry de Maraumont, PharmD, MSc5, Sarah Hodgkinson, PhD6, Kim Rand, PhD7, Jamie Sebaaly, Pharm5, Dustin Cavida, PharmD5, ISTVAN M. MAJER, PhD8, Ho Jin Kim, MD9;
1University of California San Francisco Weill Institute for Neurosciences, San Francisco, CA, USA, 2University of Oxford, Oxford, United Kingdom, 3Fukushima Medical University School of Medicine, Fukushima, Japan, 4Amgen, Uxbridge, United Kingdom, 5Amgen Inc., Thousand Oaks, CA, USA, 6Oxford PharmaGenesis, Oxford, United Kingdom, 7Maths In Health, Klimmen, Netherlands, 8Amgen Europe GmbH, Global HEOR, Rotkreuz, Switzerland, 9Research Institute and Hospital of National Cancer Center, Goyang, Korea, Republic of
1University of California San Francisco Weill Institute for Neurosciences, San Francisco, CA, USA, 2University of Oxford, Oxford, United Kingdom, 3Fukushima Medical University School of Medicine, Fukushima, Japan, 4Amgen, Uxbridge, United Kingdom, 5Amgen Inc., Thousand Oaks, CA, USA, 6Oxford PharmaGenesis, Oxford, United Kingdom, 7Maths In Health, Klimmen, Netherlands, 8Amgen Europe GmbH, Global HEOR, Rotkreuz, Switzerland, 9Research Institute and Hospital of National Cancer Center, Goyang, Korea, Republic of
OBJECTIVES: Inebilizumab is approved for aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD) based on the pivotal phase 2/3 N-MOmentum trial, while rituximab is commonly used off-label. In the absence of a head-to-head trial, this analysis compared the efficacy of inebilizumab with rituximab in reducing NMOSD attack risk.
METHODS: Following a systematic literature review and feasibility assessment, an unanchored matching-adjusted indirect comparison (MAIC) was conducted in AQP4+ patients using individual patient-level data (IPD) from N-MOmentum (n=161) and digitized IPD from a single-arm prospective rituximab study (n=21; Kim et al. Arch Neurol. 2011;68(11):1412-20). Kim et al. was the only rituximab study with extractable data for an AQP4+ subpopulation and was therefore suitable for MAIC. Rituximab therapy consisted of induction (375 mg/m2 weekly for 4 weeks or 1,000 mg twice every two weeks) followed by maintenance dosing (375 mg/m2 once) over 24 months. Time to first NMOSD attack (TTFA) was compared using investigator-determined criteria as adjudication committee-determined attacks were not reported by Kim et al. Matching covariates for the base case and scenario analyses were informed by N-MOmentum data and clinical opinion.
RESULTS: Age, annualised attack rate, and sex were selected for the base case, with alternative covariate sets evaluated in scenario analyses. In the unmatched comparison, the hazard ratio (HR) for TTFA was 0.59 (95% confidence interval [CI] 0.22−1.56) for inebilizumab versus rituximab. After matching, the effective sample size for inebilizumab was 136.6 and the HR was 0.54 (95%CI 0.20−1.44). Scenario analyses were consistent with the base case.
CONCLUSIONS: This study underscores the limited trial evidence available for rituximab monotherapy in AQP4+ NMOSD. Although the MAIC analyses suggested delaying attacks with inebilizumab versus rituximab, the small rituximab sample size resulted in wide confidence intervals precluding definitive conclusions. More robust real-world evidence is needed to confirm the relative effectiveness of inebilizumab versus rituximab in this population.
METHODS: Following a systematic literature review and feasibility assessment, an unanchored matching-adjusted indirect comparison (MAIC) was conducted in AQP4+ patients using individual patient-level data (IPD) from N-MOmentum (n=161) and digitized IPD from a single-arm prospective rituximab study (n=21; Kim et al. Arch Neurol. 2011;68(11):1412-20). Kim et al. was the only rituximab study with extractable data for an AQP4+ subpopulation and was therefore suitable for MAIC. Rituximab therapy consisted of induction (375 mg/m2 weekly for 4 weeks or 1,000 mg twice every two weeks) followed by maintenance dosing (375 mg/m2 once) over 24 months. Time to first NMOSD attack (TTFA) was compared using investigator-determined criteria as adjudication committee-determined attacks were not reported by Kim et al. Matching covariates for the base case and scenario analyses were informed by N-MOmentum data and clinical opinion.
RESULTS: Age, annualised attack rate, and sex were selected for the base case, with alternative covariate sets evaluated in scenario analyses. In the unmatched comparison, the hazard ratio (HR) for TTFA was 0.59 (95% confidence interval [CI] 0.22−1.56) for inebilizumab versus rituximab. After matching, the effective sample size for inebilizumab was 136.6 and the HR was 0.54 (95%CI 0.20−1.44). Scenario analyses were consistent with the base case.
CONCLUSIONS: This study underscores the limited trial evidence available for rituximab monotherapy in AQP4+ NMOSD. Although the MAIC analyses suggested delaying attacks with inebilizumab versus rituximab, the small rituximab sample size resulted in wide confidence intervals precluding definitive conclusions. More robust real-world evidence is needed to confirm the relative effectiveness of inebilizumab versus rituximab in this population.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
CO188
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
SDC: Rare & Orphan Diseases, SDC: Systemic Disorders/Conditions (Anesthesia, Auto-Immune Disorders (n.e.c.), Hematological Disorders (non-oncologic), Pain)