Comorbidities Are Associated With Unfavorable Outcome in Aquaporin‐4 Antibody Positive Neuromyelitis Optica Spectrum Disorders and Myelin Oligodendrocyte Glycoprotein Antibody‐Associated Disease: Exploratory Study From the <scp>CROCTINO</scp> Cohort
Sara Samadzadeh, Frederike Cosima Oertel, Hayder Salih, Ting‐Yi Lin, Seyedamirhosein Motamedi, Claudia Chien, Lawrence J. Cook, M. A. Lana-Peixoto, Mariana Andrade Fontenelle, Ho Jin Kim, Jae‐Won Hyun, S.Y. Jung, J Palace, Adriana Roca‐Fernández, Maria Isabel Leite, Srilakshmi M. Sharma, Fereshteh Ashtari, Rahele Kafieh, Alireza Dehghani, Mohsen Pourazizi, Lekha Pandit, Anitha D’Cunha, Orhan Aktaş, Marius Ringelstein, Philipp Albrecht, Eugene F. May, Caryl Tongco, Letizia Leocani, Marco Pisa, Marta Radaelli, Bernardo Sánchez‐Dalmau, Elena H. Martínez‐Lapiscina, Hadas Stiebel‐Kalish, Mark A. Hellmann, Itay Lotan, Sasitorn Siritho, de Sèze, Thomas Senger, Joachim Havla, Romain Marignier, Caroline Froment Tilikete, Álvaro Cobo‐Calvo, Denis Bernardi Bichuetti, Ivan Maynart Tavares, Kerstin Soelberg, Ayşe Altıntaş, Rengin Yıldırım, Uygur Tanrıverdi, Anu Jacob, Saif Huda, Zoe Rimler, Allyson Reid, Yang Mao‐Draayer, Pablo Villoslada, Ibis Soto de Castillo, Ari Green, Axel Petzold, Michael R. Yeaman, Terry J. Smith, Alexander U. Brandt, Hanna Zimmermann, Friedemann Paul, Nasrin Asgari
Abstract
BACKGROUND: Comorbidities occur in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and double seronegative NMOSD (DN-NMOSD), potentially contributing to a less favorable disease course. OBJECTIVES: To characterize comorbidities in AQP4-NMOSD, MOGAD, and DN-NMOSD and assess their association with optic neuritis (ON) outcomes by optical coherence tomography (OCT) in AQP4-NMOSD. METHODS: Four hundred and forty-two participants from the CROCTINO cohort were evaluated for comorbidities. RESULTS: In AQP4-NMOSD patients (n = 360), 43.5% (n = 161) had comorbidities, equally divided between single and multiple. In MOGAD (n = 49), 40.8% had comorbidities, with 75% (n = 15) single and 25% (n = 5) multiple. In DN-NMOSD (n = 33), 36.4% (n = 12) had comorbidities equally split. AQP4-NMOSD patients had more multiple comorbidities (50%, n = 81/161) than MOGAD (25%, n = 5/20, p = 0.03) and more autoimmune disorders (AID) (40.4%, n = 65) than MOGAD (20%, n = 4, p = 0.09) and DN-NMOSD (none, p = 0.004). Cardiovascular comorbidities and related risk factors (CVC/RF) occurred in 34.8% (n = 56) of AQP4-NMOSD, 50% (n = 10) of MOGAD, and 33.3% (n = 4) of DN-NMOSD. Expanded Disability Status Scale was higher in MOGAD (3.0 vs. 2.0, p = 0.006) and DN-NMOSD (5.0 vs. 2.0, p = 0.008) with comorbidities. AQP4-NMOSD patients with CVC/RF had higher ON relapse rates than those with AID (1.06 ± 3.33 vs. 0.49 ± 0.98, p < 0.001). OCT revealed reduced inner nuclear layer thickness in AQP4-NMOSD with comorbidities compared to non-comorbidity (B = -1.52, p = 0.047), more pronounced with CVC/RF (B = -2.96, p = 0.009). CONCLUSION: Comorbidities are frequent in AQP4-NMOSD and MOGAD and are associated with ON frequency and disability. These findings highlight the need for proactive comorbidity management to improve patient care.