Predictors of relapse risk and treatment response in AQP4-IgG positive and seronegative NMOSD: A multicentre study

Pakeeran Siriratnam; Paul Sanfilippo; Anneke van der Walt; Sifat Sharmin; Yi Chao Foong; Wei Zhen Yeh; Chao Zhu; Samia Joseph Khoury; Tunde Csepany; Barbara Willekens; Masoud Etemadifar; Serkan Ozakbas; Petra Nytrova; Ayse Altintas; Abdullah Al-Asmi; Bassem Yamout; Guy Laureys; Francesco Patti; Magdolna Simo; Andrea Surcinelli; Matteo Foschi; Pamela A McCombe; Raed Alroughani; José Luis Sánchez-Menoyo; Recai Turkoglu; Aysun Soysal; Jeanette Lechner Scott; Tomas Kalincik; Helmut Butzkueven; Vilija Jokubaitis; Saif Huda; Mastura Monif; MSBASE study group

doi:10.1136/jnnp-2024-334090

Predictors of relapse risk and treatment response in AQP4-IgG positive and seronegative NMOSD: A multicentre study

J Neurol Neurosurg Psychiatry. 2024 Sep 4:jnnp-2024-334090. doi: 10.1136/jnnp-2024-334090. Online ahead of print.

Authors

Pakeeran Siriratnam^{1

2

3}, Paul Sanfilippo^{1

2}, Anneke van der Walt^{1

2}, Sifat Sharmin⁴, Yi Chao Foong^{1

5}, Wei Zhen Yeh^{1

2}, Chao Zhu¹, Samia Joseph Khoury^{6

7}, Tunde Csepany⁸, Barbara Willekens^{9

10}, Masoud Etemadifar^{11

12}, Serkan Ozakbas^{13

14}, Petra Nytrova¹⁵, Ayse Altintas¹⁶, Abdullah Al-Asmi¹⁷, Bassem Yamout^{6

18}, Guy Laureys¹⁹, Francesco Patti^{20

21}, Magdolna Simo²², Andrea Surcinelli²³, Matteo Foschi^{24

25}, Pamela A McCombe^{26

27}, Raed Alroughani²⁸, José Luis Sánchez-Menoyo^{29

30}, Recai Turkoglu³¹, Aysun Soysal³², Jeanette Lechner Scott^{33

34}, Tomas Kalincik^{4

35}, Helmut Butzkueven^{1

2}, Vilija Jokubaitis¹, Saif Huda³, Mastura Monif^{36

2}; MSBASE study group

Collaborators

Affiliations

¹ Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
² Alfred Health, Department of Neurology, Melbourne, Victoria, Australia.
³ Neurology, Walton Centre for Neurology and Neurosurgery, Liverpool, UK.
⁴ Department of Medicine, CORe, University of Melbourne, Melbourne, Victoria, Australia.
⁵ Neurology, Royal Hobart Hospital, Hobart, Tasmania, Australia.
⁶ Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon.
⁷ American University of Beirut, Beirut, Lebanon.
⁸ Department of Neurology, University of Debrecen, Debrecen, Hungary.
⁹ Neurology, Universitair Ziekenhuis Antwerpen, Edegem, Belgium.
¹⁰ Faculty of Medicine and Health Sciences, Translational Neurosciences Research Group, University of Antwerp, Wilrijk, Belgium.
¹¹ Faculty of Medicine, Isfahan University of Medical sciences, Isfahan, Iran (the Islamic Republic of).
¹² Neurology, Dr. Etemadifar MS Institute, Isfahan, Iran (the Islamic Republic of).
¹³ Izmir University of Economics, Medical Point Hospital, İzmir, Turkey.
¹⁴ Multiple Sclerosis Research Association, Izmir, Turkey.
¹⁵ Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic.
¹⁶ Department of Neurology, School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Istanbul, Turkey.
¹⁷ College of Medicine & Health Sciences and Sultan Qaboos University Hospital, Sultan Qaboos University, Al-Khodh, Oman.
¹⁸ Neurology Department, Harley Street Medical Centre, Abu Dhabi, UAE.
¹⁹ Department of Neurology, Universitair Ziekenhuis Gent, Gent, Belgium.
²⁰ Neuroscience, Department of Surgical and Medical Sciences and Advanced Technologies 'G.F. Ingrassia', University of Catania, Catania, Italy.
²¹ Multiple Sclerosis Unit, AOU Policlinico G Rodolico-San Marco, University of Catania, Catania, Italy.
²² Department of Neurology, Semmelweis University, Budapest, Hungary.
²³ Department of Neuroscience, S Maria delle Croci Hospital, Ravenna, Italy.
²⁴ Department of Neuroscience, MS Center, Neurology Unit, S. Maria delle Croci Hospital, Ravenna, Italy.
²⁵ Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
²⁶ The University of Queensland, Brisbane, Queensland, Australia.
²⁷ Department of Neurology, Royal Brisbane Hospital, Brisbane, Queensland, Australia.
²⁸ Division of Neurology, Department of Medicine, Amiri Hospital, Kuwait City, Kuwait.
²⁹ Neurology, Galdakao-Usanosolo University Hospital, Osakidetza-Basque Health Service, Galdakao, Spain.
³⁰ Biocruces-Bizkaia Health Research Institute, Barakaldo, Spain.
³¹ Department of Neurology, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey.
³² Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey.
³³ Hunter Medical Research Institute, The University of Newcastle, Newcastle, New South Wales, Australia.
³⁴ Hunter New England Health, John Hunter Hospital, New Lambton Heights, New South Wales, Australia.
³⁵ Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
³⁶ Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia [email protected].

PMID: 39231582
DOI: 10.1136/jnnp-2024-334090

Abstract

Background: Neuromyelitis optica spectrum disorder (NMOSD) can be categorised into aquaporin-4 antibody (AQP4-IgG) NMOSD or seronegative NMOSD. While our knowledge of AQP4-IgG NMOSD has evolved significantly in the past decade, seronegative NMOSD remains less understood. This study aimed to evaluate the predictors of relapses and treatment responses in AQP4-IgG NMOSD and seronegative NMOSD.

Methods: This was a multicentre, international, retrospective cohort study using the MSBase registry. Recurrent relapse risk was assessed using an Andersen-Gill model and risk of first relapse was evaluated using a Cox proportional hazards model. Covariates that putatively influence relapse risk included demographic factors, clinical characteristics and immunosuppressive therapies; the latter was assessed as a time-varying covariate.

Results: A total of 398 patients (246 AQP4-IgG NMOSD and 152 seronegative NMOSD) were included. The AQP4-IgG NMOSD and seronegative NMOSD patients did not significantly differ by age at disease onset, ethnicity or annualised relapse rate. Both low-efficacy and high-efficacy immunosuppressive therapies were associated with significant reductions in recurrent relapse risk, with notably greater protection conferred by high-efficacy therapies in both AQP4-IgG NMOSD (HR 0.27, 95% CI 0.15 to 0.49, p<0.001) and seronegative NMOSD (HR 0.21, 95% CI 0.08 to 0.51, p<0.001). Longer disease duration (HR 0.97, 95% CI 0.95 to 0.99, p<0.001) and male sex (HR 0.52, 95% CI 0.34 to 0.84, p=0.007) were additional protective variables in reducing the recurrent relapse risk for the AQP4-IgG NMOSD group.

Conclusion: Although further studies are needed to improve our understanding of seronegative NMOSD, our findings underscore the importance of aggressive treatment with high-efficacy immunotherapies in both NMOSD subtypes, regardless of serostatus.

Keywords: HEALTH ECONOMICS; IMMUNOLOGY; MEDICINE; MULTIPLE SCLEROSIS; NEUROIMMUNOLOGY.