Progression independent of relapse activity and relapse-associated worsening in seronegative NMOSD: an international cohort study

• DOI: 10.1007/s00415-025-13064-6
• Publication Date: 2025-04-14T13:44:56Z
• Authors: Pakeeran Siriratnam; Saif Huda; Anneke Van der Walt; Paul Sanfilippo; Sifat Sharmin; Yi Chao Foong; Wei Zhen Yeh; Chao Zhu; Samia J. Khoury; Tunde Csepany; Barbara Willekens; Masoud Etemadifar; Serkan Ozakbas; Petra Nytrova; Ayse Altintas; Abdullah Al-Asmi; Cristina Ramo-Tello; Guy Laureys; Francesco Patti; Dana Horakova; Matteo Foschi; Cavit Boz; Pamela McCombe; Recai Turkoglu; Izanne Roos; Jeannette Lechner...; Tomas Kalincik; Vilija Jokubaitis; Helmut Butzkueven; Mastura Monif

Abstract

Background Previous studies have indicated that progression independent of relapse activity (PIRA) is uncommon in patients with aquaporin- 4 antibody-positive (AQP4-IgG) neuromyelitis optica spectrum disorder (NMOSD). However, the patterns of disability accumulation in seronegative NMOSD are unknown. This study aimed to evaluate the prevalence of PIRA and relapse-associated worsening (RAW) in seronegative NMOSD.

Methods We conducted a retrospective, multicentre cohort study of seronegative NMOSD patients from the MSBase registry. Inclusion criteria required at least three recorded expanded disability status scale (EDSS) scores: baseline, progression, and 6 months confirmed disability progression (CDP). For those with 6-month CDP, the presence or absence of relapse between baseline and progression determined the classification as RAW or PIRA, respectively. Descriptive statistics were employed to present the data.

Results This study included 93 patients, with a median follow-up duration of 5.0 years (Q1 2.8, Q3 8.4). The cohort predominantly consisted of female patients (77.4%), with a median age of onset of 33.9 years (Q1 26.1, Q3 41.2). PIRA was observed in 1 case (1.1%), whilst RAW was documented in 7 cases (7.5%).

Conclusion This international cohort study confirms that CDP is uncommon in seronegative NMOSD. Given more than three quarters of CDP occur due to RAW, therapeutic strategies should focus primarily on preventing relapses.