Oral corticosteroid dosage and taper duration at onset in myelin oligodendrocyte glycoprotein antibody-associated disease influences time to first relapse

Rheumatology and Immunology Neurology Medicine
Myelin oligodendrocyte glycoprotein antibody-associated disease Oral corticosteroids Time to relapse Dosage Taper duration

This is a multicenter retrospective cohort study on the impact of oral corticosteroid dosage and tapering duration on the time to first relapse in patients with initial presentation of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD).

Background:

MOGAD is a unique antibody-associated demyelinating disease. In both children and adults, it often manifests as bilateral or recurrent optic neuritis, transverse myelitis, and in children, it may present as acute disseminated encephalomyelitis. MOGAD episodes are generally highly responsive to corticosteroids, but long-term corticosteroid exposure can lead to adverse effects on neuropsychiatric, metabolic, and bone health. Therefore, determining an appropriate corticosteroid treatment regimen at the onset of the disease to delay the time to first relapse while minimizing cumulative exposure is of significant importance. Currently, there is a lack of consensus among clinicians regarding the optimal treatment regimen at disease onset.

Study Subjects and Methods:

The study included 109 MOGAD patients (62 females, 41 with childhood onset, median onset age 26 years) from 24 centers in Australia between July 2009 and August 2023. The relationship between the dosage of oral prednisone and the time to first relapse after MOGAD onset was analyzed using Cox proportional hazards models, and Simon-Makuch and Kaplan-Meier curves were drawn to determine the optimal dosing regimen.

Main Results:

  1. In the multivariable model, each additional 1mg/day of prednisone equivalent was associated with a 3.7% reduction in relapse risk (95% CI 0.8%-6.6%, p=0.014).
  2. A dosage of ≥12.5mg/day (children 0.16mg/kg/day) was associated with a 79% reduction in relapse risk (HR 0.21, 95% CI 0.07-0.6, p=0.0036).
  3. Maintaining a prednisone dosage of ≥12.5mg/day for at least three months after onset was associated with an 88% reduction in relapse risk (HR 0.12, 95% CI 0.03-0.44, p=0.0012).
  4. No grade 3 or higher adverse reactions occurred in patients administered the recommended dosage.
  5. This dosage could accumulate to less than 5000mg within three months, reducing the risk of high-dose corticosteroid exposure associated with subsequent relapses.

Conclusion:

At the onset of MOGAD, it is recommended that adults take 12.5mg of prednisone daily (children 0.16mg/kg/day) for at least three months to significantly delay the time to first relapse, with manageable risks of corticosteroid exposure. This study provides evidence-based medicine for the optimal corticosteroid treatment regimen at the onset of MOGAD.

Source:

This study was completed by Associate Professor Sudarshini Ramanathan and Professor Tomas Kalincik of the University of Sydney, published in the 2024 issue of the Journal of Neurology, Neurosurgery and Psychiatry. The first author is Benjamin P Trewin, and the corresponding author is Associate Professor Sudarshini Ramanathan.

Research Workflow:

  1. Retrospectively included 109 MOGAD patients from 24 centers in Australia.
  2. Collected detailed clinical, treatment (including dosage and duration), and prognosis data from patients with a minimum follow-up of 12 months.
  3. Divided patients into child (≤16 years) and adult groups. Converted intravenous and oral corticosteroid dosages to equivalent adult dosages.
  4. Analyzed the relationship between the daily dosage of oral corticosteroids (independent variable) and time to first relapse (TTFR) (dependent variable), and plotted Simon-Makuch survival curves to determine the minimum effective dosage threshold.
  5. Divided patients into four groups based on the duration of maintaining the threshold dosage post-onset. Used Kaplan-Meier curves and Cox models to determine the minimum duration for maintaining the threshold dosage.
  6. Analyzed the relapse rates and the proportion developing a non-relapsing course among patients administered the recommended dosage.
  7. Stated adverse reaction occurrence statistics.

Significance:

  1. This study provides the first evidence-based recommendation for the optimal oral corticosteroid dosage and duration at the onset of MOGAD.
  2. Showed that sufficient dosage and duration of oral corticosteroids at disease onset could significantly delay the first relapse and increase the likelihood of maintaining a monophasic course.
  3. Also recognized the risk of adverse reactions due to excessive cumulative dosage.
  4. Provides important basis for improving the initial treatment and long-term prognosis for both child and adult MOGAD patients.

Features:

  1. Large sample size, including both child and adult cases.
  2. Explored the quantitative relationship between oral corticosteroid dosage and duration on the time to first relapse.
  3. Provided evidence-based recommendations for optimal dosage and duration.
  4. Considered the balance between cumulative dosage and the risk of adverse reactions.
  5. Multicenter retrospective study enhances the generalizability of the results.