A single relapse induces worsening of disability and health-related quality of life in patients with neuromyelitis optica spectrum disorder

Achim Berthele; Michael Levy; Dean M Wingerchuk; Sean J Pittock; Shulian Shang; Adrian Kielhorn; Minying Royston; Guido Sabatella; Jacqueline Palace

doi:10.3389/fneur.2023.1099376

A single relapse induces worsening of disability and health-related quality of life in patients with neuromyelitis optica spectrum disorder

Front Neurol. 2023 Apr 11:14:1099376. doi: 10.3389/fneur.2023.1099376. eCollection 2023.

Authors

Achim Berthele¹, Michael Levy², Dean M Wingerchuk³, Sean J Pittock⁴, Shulian Shang⁵, Adrian Kielhorn⁵, Minying Royston⁵, Guido Sabatella⁵, Jacqueline Palace⁶

Affiliations

¹ Department of Neurology, School of Medicine, Technical University Munich, Klinikum Rechts der Isar, München, Germany.
² Massachusetts General Hospital and Harvard Medical School, Mass General Neurology, Boston, MA, United States.
³ Mayo Clinic, Scottsdale, AZ, United States.
⁴ Mayo Clinic, Rochester, MN, United States.
⁵ Alexion, AstraZeneca Rare Disease, Boston, MA, United States.
⁶ Department of Clinical Neurology, John Radcliffe Hospital, Oxford, United Kingdom.

Abstract

Background: Cumulative damage from multiple relapses in neuromyelitis optica spectrum disorder (NMOSD) is associated with poor health-related quality of life (HRQoL) and long-term disability in patients positive for anti-aquaporin 4 antibodies (AQP4+). This study assessed the effect of an individual relapse on HRQoL and disability outcomes in AQP4+ NMOSD.

Methods: Post hoc analyses of data pooled from the PREVENT study and its open-label extension, which evaluated the efficacy and safety of eculizumab in AQP4+ NMOSD, examined the effect of a single relapse on 3 disability and 4 HRQoL outcome measures. Assuming the effect of 1 relapse extends to multiple relapses, an extrapolation was done to assess the effect of 2 relapses on these outcomes.

Results: In 27 patients (placebo: n = 20; eculizumab: n = 7) experiencing an independently adjudicated relapse, 1 relapse led to significantly worse disability (modified Rankin Scale and Expanded Disability Status Scale [EDSS]) and HRQoL (36-item Short-Form Health Survey mental and physical component summaries; European Quality of Life 5-Dimension questionnaire 3-Level visual analogue scale and utility index) scores. In 4 of 7 outcomes, clinically meaningful worsening was more likely for relapsing versus non-relapsing patients (n = 116). Extrapolating the effect of 2 relapses predicted that clinically meaningful worsening was more likely in 6 out of 7 outcomes, including EDSS, for patients experiencing multiple relapses versus patients experiencing no relapses.

Conclusion: Findings from these clinical trial data demonstrate that a single NMOSD relapse can worsen disability and HRQoL, underscoring the role of relapse prevention in improving long-term outcomes in patients with AQP4+ NMOSD.

Keywords: AQP4; HRQoL – health-related quality of life; eculizumab; neuromyelitis optica; relapse.