Majority of Long-Term Immunotherapy-Treated Patients With MOGAD Sustain Relapses

Aisha A. Elfasi, MD

A recent multicenter retrospective analysis of 70 patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) demonstrated that majority of patients sustained relapses on long-term immunotherapies, including rituximab (Rituxan, Genentech), mycophenolate mofetil (CellCept; Genentech), and intravenous immunoglobulins (IVIG).¹ The findings provide evidence on the timing of relapses and immunotherapy efficacy for determining the most effective therapy regimens for preventing or reducing relapses.

Fifty-precent of patients with MOGAD remained relapse-free on rituximab (14 of 28) and mycophenolate mofetil (5 of 10), whereas 63.6% of patients treated with IVIG (7 of 11) remained relapse-free, with those in the IVIG group experiencing a slightly lower relapse rate.¹

The results were presented as a poster at the annual Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum held February 23-25, 2023, in San Diego, California, by lead author Aisha A. Elfasi, MD, educational chief resident at the University of Florida College of Medicine. In this analysis, investigators assessed the timing of relapses in MOGAD and treatment response to different long-term immunotherapies.

Cases of patients with MOGAD were collected from the University of Florida, Baylor College of Medicine and the University of California San Diego. The cases were identified by review with the ICD10 diagnosis code G36 and the individual institution's neuromyelitis optica spectrum disorder (NMOSD)/MOGAD clinical databases.

Seventy patients with MOGAD were identified: 24 from the University of Florida, 13 from Baylor College of Medicine, and 33 from the University of California, San Diego. The median age of patients at symptom onset was 28.5 years (range, 1-65), and 60% of the cohort were women. Approximately 65% of patients experienced a relapsing disease course (n = 46).

In the first year, 73.9% of patients experienced their first relapse (n = 34/46), and 17.4% of patients experienced their first relapse more than 4 years (4-15 years) after initial presentation (n = 8/46). Eighty-seven percent of patients were initiated on long-term immunotherapy often after the first relapse (n = 40/46).

“The majority of our MOGAD cohort sustained relapses. While a relapsing course mostly becomes evident within the first year, a relapse may also occur years after the initial episode,” Elfasi et al wrote.¹ “Randomized controlled trials are needed to further evaluate the safety and efficacy of long-term immunotherapy in relapsing MOGAD.”

In August 2022, a study published in the European Journal of Neurology added to the available evidence supporting rituximab in the treatment of NMOSD, with the findings of the retrospective study suggesting reduced-dose rituximab is superior to azathioprine and mycophenolate mofetil.² Risk of NMOSD relapse was significantly reduced in patients treated with rituximab compared with those on azathioprine (HR, 4.40; 95% CI, 1.41-13.80; P = .011) or mycophenolate mofetil (HR, 5.20; 95% CI, 1.60-16.86; P = .006). Notably, drug discontinuations were also less likely for those in the rituximab group compared with the azathioprine group (HR, 2.22; 95% CI, 1.34-3.66; P = .002). As for safety, the rituximab group displayed a lower incidence of AEs (32.7%) than the azathioprine group (62.3%; P <.001).

In April 2022, research on adults with MOGAD showed that treatment with maintenance IVIG was associated with a reduction in disease relapse.³ The higher rate of disease relapse in patients who received lower or less frequent IVIG dosing suggested a dose response with fewer relapses at higher doses. When receiving IVIG treatment, the observed median annualized relapse rate improved to 0 (range, 0-3) from median rates of 1.4 (range, 0-6.1) prior to receiving the therapy (t108 = 7.14; P <.001). The study also showed no difference in relapse rates among those who used IVIG as a firstline therapy or not.

In November 2021, a retrospective observational study from Johns Hopkins resulted in rituximab treatment being significantly associated with a reduced relapse rate for patients with NMOSD and MOGAD.⁴ After rituximab was initiated in both NMOSD (median, annualized relapse rate [ARR]: pretreatment, 1.1; post treatment, 0; P <.001) and MOGAD (median ARR: pretreatment, 1.9, post treatment, 0.3; P = .002), the ARR decreased. Relapses on rituximab occurred in 28% of NMOSD patients (n = 31) and 61% of MOGAD patients (n = 14).

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REFERENCES
1. Elfasi A, Alkabie S, Rodriguez E, et al. Treatment Response to Different Immunotherapies in Relapsing Myelin-Oligodendrocyte Glycoprotein Antibody - Associated Disease (MOGAD) Presented at ACTRIMS Forum 2023; February 23-25; San Diego, California. Abstract P337.
2. Huang W, Wang L, Xia J, et al. Efficacy and safety of azathioprine, mycophenolate mofetil, and reduced dose of rituximab in neuromyelitis optica spectrum disorder. Eur J Neurol. 2022;29(8):2343-2354. doi:10.1111/ene.15355
3. Chen JJ, Huda S, Hacohen Y, et al. Association of maintenance intravenous immunoglobulin with prevention of relapse in adult myelin oligodendrocyte glycoprotein antibody-associated disease. JAMA Neurol. Published online April 4, 2022. doi:10.1001/jamaneurol.2022.0489
4. Ringelstein M, Ayzenberg I, Lindenblatt G, et al. Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG-Associated Disease and Neuromyelitis Optica Spectrum Disorders. Neurol Neuroimmunol Neuroinflamm. 2021;9(1):e1100. doi:10.1212/NXI.0000000000001100