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Multicenter Study
. 2024 Oct 1;81(10):1073-1084.
doi: 10.1001/jamaneurol.2024.2811.

Time to Treat First Acute Attack of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

Young Nam Kwon  1   2 , Boram Kim  3 , Jun-Soon Kim  4 , Kyung Seok Park  4 , Da-Young Seo  5 , Hyunjin Kim  5 , Eun-Jae Lee  5 , Young-Min Lim  5 , Hyunjin Ju  6 , Yeon Hak Chung  7 , Ju-Hong Min  8 , Tai-Seung Nam  9 , Sooyoung Kim  10 , Eunhee Sohn  10 , Kyong Jin Shin  11 , Jin Myoung Seok  12 , Sunyoung Kim  13 , Jong Seok Bae  14 , Sukyoon Lee  15 , Seong-Il Oh  16 , Yu Jin Jung  17 , Jinseok Park  18 , Seung Hyun Kim  18 , Ki Hoon Kim  19   20 , Ho Jin Kim  19 , Jae Ho Jung  21 , Seong-Joon Kim  21 , Seung Woo Kim  1 , Myoung-Jin Jang  22 , Jung-Joon Sung  3 , Patrick Waters  23 , Ha Young Shin  1 , Sung-Min Kim  2   3
Affiliations
Multicenter Study

Time to Treat First Acute Attack of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

Young Nam Kwon et al. JAMA Neurol. .

Abstract

Importance: A proportion of people with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) have a relapsing disease course and persistent anti-myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) seropositivity. Few studies have investigated whether treatment of the first MOGAD attack is associated with the long-term disease course and/or MOG-IgG seronegative conversion.

Objective: To investigate the association of time to treat the first acute MOGAD attack with relapse risk and MOG-IgG serostatus.

Design, setting, and participants: This was a retrospective, nationwide, multicenter cohort study involving 14 secondary or tertiary hospitals in South Korea between November 2009 and August 2023. People with adult-onset MOGAD, who either had a relapse or were followed up for more than 12 months after disease onset and had a detailed medical record of their first attack, were included. Individuals were excluded for adolescent-onset MOGAD or short disease duration.

Exposures: Patients were categorized based on the time to treat the first acute MOGAD attack: early (<5 days), intermediate (5-14 days), and late (not treated within 14 days).

Main outcomes and measures: A multivariable analysis for clinical and treatment factors associated with relapsing disease course and/or MOG-IgG seronegative conversion. Further subgroup analyses were conducted among those without long-term nonsteroidal immunosuppressant (NSIS) maintenance treatment.

Results: Among the 315 individuals screened, 75 were excluded. A total of 240 patients (median [IQR] age at onset, 40.4 [28.8-56.1] years; 125 female [52.1%]) with median (IQR) disease duration of 3.07 (1.95-6.15) years were included. A total of 110 of 240 patients (45.8%) relapsed after a median (IQR) of 0.45 (0.18-1.68) years, and 29 of 116 patients (25.0%) experienced a conversion to seronegative MOG-IgG. Both the time to treatment of the first MOGAD attack (late vs early: adjusted hazard ratio [aHR], 2.64; 95% CI, 1.43-4.84; P = .002; intermediate vs early: aHR, 2.02; 95% CI, 1.10-3.74; P = .02) and NSIS maintenance treatment (aHR, 0.24; 95% CI, 0.14-0.42; P < .001) were independently associated with the risk of relapse. In a subgroup without NSIS maintenance, the time to treat of the first MOGAD attack was still associated with higher risk of relapse (late vs early: aHR, 3.51; 95% CI, 1.64-7.50; P = .001; intermediate vs early: aHR, 2.68; 95% CI, 1.23-5.85; P = .01). Lastly, the time to treat of the first MOGAD attack was also associated with MOG-IgG seronegative conversion (early vs late: adjusted odds ratio, 7.04; 95% CI, 1.58-31.41; P = .01), whereas NSIS maintenance treatment was not.

Conclusions and relevance: Results of this cohort study suggest that early treatment of the first acute MOGAD attack was associated with a reduction in the proportion of relapsing disease course and an increase in the likelihood of MOG-IgG seronegative conversion. These data suggest that timing of acute phase treatment for the first MOGAD attack can be associated with the long-term prognosis and autoimmune status of patients.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Kwon reported receiving grants from the National Research Foundation of Korea, the Korean Neurological Association and Eisai; personal fees from Eisai, Celltrion, GC Pharma, Merck Serono, Roche, Sanofi Genzyme, and CorestemChemon outside the submitted work. Dr Min reported receiving funding from the National Research Foundation of Korea (MIST and KHIDI) and the SMC Research and Development grant; and consultation/speaker fees from Bayer Healthcare, Merk, Biogen Idec, Sanofi, UCB, Samsung Bioepis, Mitsubishi Tanabe, Celltrion, Roche, Janssen, Eisai, and AstraZeneca. Dr H.J. Kim reported receiving grants from the National Research Foundation of Korea, AprilBio, Eisai, and UCB and personal fees from Alexion, Altos Biologics, AstraZeneca, Biogen, Daewoong Pharmaceutical, Eisai, GC Pharma, Handok Pharmaceutical, Kaigene, Kolon Life Science, MDimune, Merck Serono, Mitsubishi Tanabe Pharma, Roche, and Sanofi Genzyme outside the submitted work. Dr Waters reported receiving speaker fees from Alexion, UCB, and F. Hoffmann-La Roche; having a patent with royalties paid from Euroimmun AG, patents 10802019 and 10877033 issued, and a patent 20210071249 pending; and being codirector of a laboratory that runs tests for targets relevant to autoimmune neurology including anti–myelin oligodendrocyte glycoprotein immunoglobulin G. Dr H. Shin reported receiving grants from the National Research Foundation of Korea by the South Korea government (MSIT) and personal fees from Alexion, Astellas, AstraZeneca, Biogen, Daewoong Pharmaceutical, Eisai, Euroimmun, GC Pharma, Genuv, Genzyme, Handok Pharmaceutical, Janssen, Merck Serono, Mitsubishi Tanabe Pharma, Roche, Sanofi, and UCB outside the submitted work. Dr S.M. Kim reported receiving lecture/consultation fees from Bayer Schering Pharma, Genzyme, Merck Serono, and UCB; a grant from the National Research Foundation of Korea and the Korea Health Industry Development Institute Research; and serving as associate editor of the Journal of Clinical Neurology. Dr S.M. Kim and Seoul National University Hospital have transferred the technology of flow cytometric autoantibody assay to EONE Laboratory, Korea. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart of Study Participants and Their Treatment
A, Study participants. B, Treatment for study participants. MOGAD indicates myelin oligodendrocyte glycoprotein antibody-associated disease; NSIS, nonsteroidal immunosuppressant. aDetailed medical record of the onset and treatment history of the first attack with dates.
Figure 2.
Figure 2.. Factors Associated With Relapse and Kaplan-Meier (KM) Curve for the Cumulative Probability of Relapse
A, Analysis for factors associated with relapsing myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) course revealed that both the time to treat the first acute MOGAD attack and a lack of nonsteroidal immunosuppressant treatment were independently associated with higher risk of relapse. B, KM curve for the cumulative probability of relapse revealed higher risk of relapse course in the late group vs the early group. The cumulative probability of a relapse was not significantly different between the intermediate and early groups. C, Among the 141 patients without nonsteroidal immunosuppressant maintenance, only the time to treat the first acute MOGAD attack was associated with higher risk of relapse. D, The early group showed a lower risk of having a relapsing disease course than the late group. aHR indicates adjusted hazard ratio; CS, corticosteroid; EDSS, Kurtzke expanded disability status scale; NSIS, nonsteroidal immunosuppressant; OCB, oligoclonal band; PLEX, plasma exchange.
Figure 3.
Figure 3.. Early Treatment Increases Anti–Myelin Oligodendrocyte Glycoprotein Immunoglobulin G (MOG-IgG) Seronegative Conversion in Patients With Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD)
A, In univariable and multivariable binary logistic analysis, the earlier time to treat the first acute MOGAD attack the higher likelihood of seronegative conversion. Female sex was independently associated with the higher likelihood of becoming seronegative. B, The prevalence of MOG-IgG seronegative conversion was higher in the early treatment group compared with the late group (P = .009). Whiskers indicate 95% CIs. aOR indicates adjusted odds ratio; CSF, cerebrospinal fluid; CS, corticosteroid; EDSS, Kurtzke expanded disability status scale; IVIG, intravenous immunoglobulin; NS, not significant; OCB, oligoclonal band; OR, odds ratio; PLEX, plasma exchange; WBC, white blood cells.
Figure 4.
Figure 4.. Serologic Status and Disease Course Over Time in the Total 240 Participants
Each bar represents an individual participant, and the end of each bar indicates the last follow-up. The length of the purple bars indicates the time from onset to treatment at the first myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) attack. Patients with full red bar were not treated within 30 days from onset. Dark green bars indicate seropositive status, and light blue bars indicate seronegative status. Light green bars indicate unknown serologic status as the period before the first anti–myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) test. Red circles indicate clinical relapses, and black diamonds indicate the MOG-IgG test.
See this image and copyright information in PMC

References

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