Relapse rates differ by maintenance treatment; MS drugs appear ineffective in retrospective study

Maintenance immunotherapy with IV immunoglobulin (IVIG) was more effective than other therapies in myelin oligodendrocyte glycoprotein–immunoglobulin G (MOG-IgG) associated disorder (MOGAD), a retrospective study found.

In 70 patients with MOG antibodies and relapsing disease, the median pre-treatment annualized relapse rate (ARR) was 1.6. On maintenance immunotherapy for 6 months or longer, the proportion of patients with relapse was 20% with IVIG (2 of 10 patients; ARR 0), 59% with azathioprine (13 of 22; ARR 0.2), 61% with rituximab (22 of 36; ARR 0.59), and 74% with mycophenolate mofetil (14 of 19; ARR 0.67), reported John Chen, MD, PhD, of Mayo Clinic in Rochester, Minnesota and coauthors.

The overall median ARR on these four treatments was 0.3, they wrote in Neurology. Some patients were treated with more than one agent. Patients treated with multiple sclerosis (MS) disease-modifying agents (n=9, including interferon beta, glatiramer acetate, and fingolimod) all had a breakthrough relapse on treatment (ARR 1.5).

“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,” Chen and coauthors wrote. “Traditional MS disease-modifying agents appear to be ineffective. Prospective randomized controlled studies are required to validate these conclusions.”

In an accompanying editorial, Patrick Waters, PhD, FRCPath, and Jacqueline Palace, FRCP, DM, both of University of Oxford in England, wrote that the “the study by Chen et al. supports the use of maintenance IVIG in those who fail first-line therapies. This study adds to the discordant literature on treatment of patients with MOG antibodies and highlights a paucity of evidence to guide clinical decisions.”

It also adds to “a small body of literature with conflicting data on the utility of different immunotherapies to prevent relapses in MOG antibody–positive patients,” they continued. “Some studies favor steroids, azathioprine, mycophenolate, IVIG, or rituximab, while others advise caution with steroids (in children) or rituximab. Varied follow-up times and indication bias in the different treatment arms of these studies may have influenced outcomes.”

MOG antibodies are seen in both health and disease states and may cause monophasic or relapsing disorders associated with demyelination. MOG-associated symptoms may present differently in different age groups. Acute disseminating encephalomyelitis (ADEM) is most common in children under 11, though up to half in that age group with ADEM may not have MOG antibodies. In more extensive syndromes — ADEM with transverse myelitis or optic neuritis, for example — MOG positivity and relapse are more common. In older children and adults, optic neuritis is the more common presentation. These sources of variability make treatment choice, as well as clinical trial evaluation, complex.

Chen and colleagues studied 70 symptomatic, relapsing MOG-positive patients (59% female) who had been treated for 6 or more months with one or more immune-modulating drugs including IVIG, mycophenolate mofetil, rituximab, azathioprine, interferon beta, glatiramer acetate, and fingolimod. They included 47 adults (18 or older) and 23 children (younger than 18) seen at the Mayo Clinic between January 2001 and April 2019, or elsewhere between 2016 and 2019. No patient had aquaporin-4 (AQP4)-IgG positivity.

The median age at initial CNS demyelinating attack was 29 years (range 3-61 years; 33% <18 years). Presenting symptoms included isolated optic neuritis (47%), transverse myelitis (11%), AQP4-IgG seronegative neuromyelitis optic spectrum disorder (NMOSD; 10%), and ADEM with or without other findings (31%).

Relapses were defined as any new central nervous system sign or symptom lasting 24 hours and supported by clinical or radiologic findings. The median number of demyelinating attacks was 5 over a median follow-up of 4.5 years.

Relapses included optic neuritis (96%), transverse myelitis (49%), ADEM (40%), and AQP4-IgG seronegative NMOSD (27%).

“The relapse rate was 20% in the 10 patients treated with IVIG compared with 63% in the 78 patients treated with the other non-MS therapies,” the editorialists observed. “The IVIG group contained the greatest proportion of children. This observation, along with the results of a previous pediatric study, suggests that adults and children may need to be treated differently.”

“Randomized controlled treatment trials are needed, but age-related differences in presentation, relapse rates, and outcomes need to be considered,” they added. “In their absence, propensity-matched observational studies in larger populations would be informative, particularly when one considers the worldwide shortage of IVIG and its substantial cost.”

Limitations of the study include its retrospective design, variable periods of follow-up, and non-randomized treatment selection. Some patients received more than one treatment. The study cohort also was largely from tertiary care centers and may not be generalizable to other, possibly less severely affected, populations. “Conclusions drawn from this study about the efficacy of immunotherapy apply best to MOG IgG–positive patients with recurrent disease,” the authors noted.

  1. Maintenance immunotherapy with IV immunoglobulin (IVIG) for 6 months or longer was more effective than other therapies in myelin oligodendrocyte glycoprotein–immunoglobulin G (MOG-IgG) associated disorder (MOGAD), a retrospective study found.

  2. Children made up most of the group treated with IVIG, suggesting adults and children may need to be treated differently.

Paul Smyth, MD, Contributing Writer, BreakingMED™

This work was supported by the Department Laboratory Medicine and Pathology and the Center for MS and Autoimmune Neurology, Mayo Clinic in Rochester, MN. This work was also supported by the Leonard and Mary Lou Hoeft Career Development Award in Ophthalmology Research.

Chen reports no disclosures.

Waters and the University of Oxford are named inventors on patents for antibody assays and have received royalties. He has received honoraria or research funding from Alexion, Biogen Idec, Mereo Biopharma, Retrogenix, UBC, and Euroimmun AG and travel grants from the Guthy-Jackson Charitable Foundation.

Palace has received support for scientific meetings and honorariums for advisory work from Merck Serono, Biogen Idec, Novartis, Teva, Chugai Pharma, Bayer Schering, Alexion, Roche, Genzyme, MedImmune, Euroimmun, MedDay, Abide ARGENX, UCB, and Viela Bio and grants from Merck Serono, Novartis, Biogen Idec, Teva, Abide, MedImmune, Bayer Schering, Genzyme, Chugai, and Alexion. She has received grants from the MS Society, Guthy-Jackson Charitable Foundation, National Institute for Health Research, Oxford Health Services Research Committee, Medical Research Council, Grant for Multiple Sclerosis Innovation, John Fell, and Myaware for research studies.

Cat ID: 130

Topic ID: 82,130,730,130,138,192,925