Amy Kunchok1, Charles Malpas2, Petra Nytrova3, Eva Kubala Havrdova3, Raed Alroughani4, Murat Terzi5, Bassem Yamout6, Jyh Yung Hor7, Rana Karabudak8, Cavit Boz9, Serkan Ozakbas10, Javier Olascoaga11, Magdolna Simo12, Franco Granella13, Francesco Patti14, Pamela McCombe15, Tunde Csepany16, Bhim Singhal17, Roberto Bergamaschi18, Yara Fragoso19, Talal Al-Harbi20, Recai Turkoglu21, Jeannette Lechner-Scott22, Guy Laureys23, Celia Oreja-Guevara24, Eugenio Pucci25, Patrizia Sola26, Diana Ferraro26, Ayse Altintas27, Aysun Soysal28, Steve Vucic29, Francois Grand'Maison30, Guillermo Izquierdo30, Sara Eichau31, Alessandra Lugaresi32, Marco Onofrj33, Maria Trojano34, Mark Marriott35, Helmut Butzkueven36, Ilya Kister37, Tomas Kalincik38. 1. CORe, Department of Medicine, University of Melbourne, Melbourne, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia. Electronic address: kunchok.amy@mayo.edu. 2. CORe, Department of Medicine, University of Melbourne, Melbourne, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia. 3. Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic. 4. Division of Neurology, Department of Medicine, Amiri Hospital, P.O.Box 1661. Qurtoba, Sharq, 73767, Kuwait. 5. Medical Faculty, 19 Mayis University, Kurupelit, Samsun, 55160, Turkey. 6. Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon. 7. Department of Neurology, Penang General Hospital, Penang, Malaysia. 8. Hacettepe University, Sihhiye, Ankara, 6100, Turkey. 9. KTU Medical Faculty Farabi Hospital, Karadeniz Technical University, Trabzon, 61080, Turkey. 10. Dokuz Eylul University, Cumhuriyet Blv 144, Konak/Izmir, 35220, Turkey. 11. Instituto Vasco de Investigación Sanitaria, Hospital UniversitarioDonostia, Paseo de Begiristain, San Sebastián, 20014, Spain. 12. Semmelweis University Budapest, Balassa, Budapest, 1083, Hungary. 13. Department of Medicine and Surgery, University of Parma, via Gramsci 14, Parma, 43126, Italy. 14. GF Ingrassia Department, University of Catania, Policlinico G Rodolico Via Santa Sofia 78, 95123 Catania, Italy. 15. Department of Neurology, Royal Brisbane and Women's Hospital, Herston, Brisbane, 4029, Australia. 16. Department of Neurology, Faculty of Medicine, University of Debrecen, Moricz Zs. krt 22, Debrecen, 4032, Hungary. 17. Bombay Hospital Institute of Medical Sciences, Mumbai, Maharashtra 400020, India. 18. IRCCS Mondino Foundation, via Mondino 2, Pavia, 27100, Italy. 19. Universidade Metropolitana de Santos, Santos, Brazil. 20. Neurology Department, King Fahad Specialist Hospital-Dammam, Al Muraikebat Area, Ammar Bin Thabet Street. P.O. Box 15215, Dammam 31444, Saudi Arabia. 21. Haydarpasa Numune Training and Research Hospital, Selimiye Mahallesi, Istanbul, 34668, Turkey. 22. School of Medicine and Public Health, Department of Neurology, University Newcastle, Lookout Road, John Hunter Hospital, Hunter New England Health, Newcastle, 2305, Australia. 23. Universitary Hospital Ghent, Corneel Heymanslaan 10, 9000 Ghent, Belgium. 24. Hospital Universitario La Paz, Madrid, Spain. 25. UOC Neurologia, Azienda Sanitaria Unica Regionale Marche - AV3, Via Santa Lucia 2, Macerata, 62100, Italy. 26. Department of Neuroscience, Azienda Ospedaliera Universitaria, via giardini 1355, Modena, 41100, Italy. 27. Koc University, School of Medicine, Department of Neurology, Davutpasa, Istanbul, Turkey. 28. Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey. 29. Department of Neurology, Westmead Hospital, NSW 2145, Sydney, Australia. 30. Neuro Rive-Sud, 4896 boul. Taschereau, suite 250, Quebec, J4V 2J2, Canada. 31. Hospital Universitario Virgen Macarena, Dr Fedriani 3, Sevilla, 41009, Spain. 32. IRCCS Istituto delle Scienze Neurologiche di Bologna, University of Bologna, Via Altura 3A, 40139, Bologna, Italy; Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Italy. 33. Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Italy. 34. Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy. 35. Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia. 36. Monash University, Department of Neurology, Alfred Hospital, Melbourne, Australia. 37. New York University Langone Medical Center, 240 East 38th St, New York, 10016, United States. 38. CORe, Department of Medicine, University of Melbourne, Melbourne, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia. Electronic address: tomas.kalincik@unimelb.edu.au.
Abstract
BACKGROUND: Aquaporin-4-IgG positive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD) is an uncommon central nervous system autoimmune disorder. Disease outcomes in AQP4-IgG+NMOSD are typically measured by relapse rate and disability. Using the MSBase, a multi-centre international registry, we aimed to examine the impact immunosuppressive therapies and patient characteristics as predictors of disease outcome measures in AQP4-IgG+NMOSD. METHOD: This MSBase cohort study of AQP4-IgG+NMOSD patients examined modifiers of relapse in a multivariable proportional hazards model and expanded disability status score (EDSS) using a mixed effects model. RESULTS: 206 AQP4-IgG+ patients were included (median follow-up 3.7 years). Age (hazard ratio [HR] = 0.82 per decade, p = 0.001), brainstem onset (HR = 0.45, p = 0.009), azathioprine (HR = 0.46, p<0.001) and mycophenolate mofetil (HR = 0.09, p = 0.012) were associated with a reduced risk of relapse. A greater EDSS was associated with age (β = 0.45 (per decade), p<0.001) and disease duration (β = 0.07 per year, p<0.001). A slower increase in EDSS was associated with azathioprine (β = -0.48, p<0.001), mycophenolate mofetil (β = -0.69, p = 0.04) and rituximab (β = -0.35, p = 0.024). INTERPRETATION: This study has demonstrated that azathioprine and mycophenolate mofetil reduce the risk of relapses and disability progression is modified by azathioprine, mycophenolate mofetil and rituximab. Age and disease duration were the only patient characteristics that modified the risk of relapse and disability in our cohort.
BACKGROUND: Aquaporin-4-IgG positive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD) is an uncommon central nervous system autoimmune disorder. Disease outcomes in AQP4-IgG+NMOSD are typically measured by relapse rate and disability. Using the MSBase, a multi-centre international registry, we aimed to examine the impact immunosuppressive therapies and patient characteristics as predictors of disease outcome measures in AQP4-IgG+NMOSD. METHOD: This MSBase cohort study of AQP4-IgG+NMOSDpatients examined modifiers of relapse in a multivariable proportional hazards model and expanded disability status score (EDSS) using a mixed effects model. RESULTS: 206 AQP4-IgG+ patients were included (median follow-up 3.7 years). Age (hazard ratio [HR] = 0.82 per decade, p = 0.001), brainstem onset (HR = 0.45, p = 0.009), azathioprine (HR = 0.46, p<0.001) and mycophenolate mofetil (HR = 0.09, p = 0.012) were associated with a reduced risk of relapse. A greater EDSS was associated with age (β = 0.45 (per decade), p<0.001) and disease duration (β = 0.07 per year, p<0.001). A slower increase in EDSS was associated with azathioprine (β = -0.48, p<0.001), mycophenolate mofetil (β = -0.69, p = 0.04) and rituximab (β = -0.35, p = 0.024). INTERPRETATION: This study has demonstrated that azathioprine and mycophenolate mofetil reduce the risk of relapses and disability progression is modified by azathioprine, mycophenolate mofetil and rituximab. Age and disease duration were the only patient characteristics that modified the risk of relapse and disability in our cohort.