Steroid-sparing maintenance immunotherapy for MOG-IgG associated disorder

Abstract

Objective: Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) associated disorder (MOGAD) often manifests with recurrent CNS demyelinating attacks. The optimal treatment for reducing relapses is unknown. To help determine the efficacy of long-term immunotherapy in preventing relapse in patients with MOGAD, we conducted a multicenter retrospective study to determine the rate of relapses on various treatments.

Methods: We determined the frequency of relapses in patients receiving various forms of long-term immunotherapy for MOGAD. Inclusion criteria were history of ≥1 CNS demyelinating attacks, MOG-IgG seropositivity, and immunotherapy for ≥6 months. Patients were reviewed for CNS demyelinating attacks before and during long-term immunotherapy.

Results: Seventy patients were included. The median age at initial CNS demyelinating attack was 29 years (range 3-61 years; 33% <18 years), and 59% were female. The median annualized relapse rate (ARR) before treatment was 1.6. On maintenance immunotherapy, the proportion of patients with relapse was as follows: mycophenolate mofetil 74% (14 of 19; ARR 0.67), rituximab 61% (22 of 36; ARR 0.59), azathioprine 59% (13 of 22; ARR 0.2), and IV immunoglobulin (IVIG) 20% (2 of 10; ARR 0). The overall median ARR on these 4 treatments was 0.3. All 9 patients treated with multiple sclerosis (MS) disease-modifying agents had a breakthrough relapse on treatment (ARR 1.5).

Conclusion: This large retrospective multicenter study of patients with MOGAD suggests that maintenance immunotherapy reduces recurrent CNS demyelinating attacks, with the lowest ARR being associated with maintenance IVIG therapy. Traditional MS disease-modifying agents appear to be ineffective. Prospective randomized controlled studies are required to validate these conclusions.

Figure 1. Disease activity of patients with MOG-IgG associated disorder on maintenance immunotherapy

Depictions of attacks before and after maintenance immunotherapy was started (time 0) for patients treated with (A) azathioprine, (B) mycophenolate mofetil, (C) rituximab, (D) maintenance IV immunoglobulin (IVIG), and (E) multiple sclerosis (MS) disease-modifying agents. Each dash represents a demyelinating attack (red indicates first-line therapy; green, second-line therapy; blue, third-line therapy; purple, fourth-line therapy). Red circle indicates immunotherapy switch, and purple indicates cessation of treatment. Blue circle indicates the last follow-up evaluation. The y-axis has the patient identifiers (IDs) arranged from old to young with a line demarking the split between adult and pediatric patients. Red open circle adjacent to the y-axis indicates relapses that occurred >50 months before the immunotherapy was started. Blue open circle at the right of the plot indicates a relapse >50 months after the immunotherapy was started. Dash along the x-axis demarks when the maintenance immunotherapy becomes fully active and a relapse is considered a failure of therapy. As an example, the top line (patient 3) in panel A shows an individual who was treated with azathioprine as a second-line therapy. Within the 50 months before starting azathioprine, the patient had 4 attacks (green hashmarks) while on a MS disease-modifying agent (E), and the red circle adjacent to the y-axis indicates there were relapses >50 months before azathioprine was initiated. At time point 0, the patient was changed to azathioprine and did not have any relapses over the 2 years of follow-up (blue circle).

Figure 2. Kaplan–Meier estimates of time to relapse on different maintenance therapies

Kaplan Meier curves showing time to relapse for patients treated with (A) azathioprine, (B) mycophenolate mofetil, (C) rituximab, (D) maintenance IV immunoglobulin (IVIG), and (E) multiple sclerosis (MS) disease-modifying agents. dash Along the x-axis demarks when the maintenance immunotherapy becomes fully active and a relapse is considered a failure of therapy.