DMTs Tied to Lower MS Relapse During Reproductive Therapy

WEST PALM BEACH, Florida — Women with multiple sclerosis (MS) undergoing assisted reproductive technologies (ART) have an increased relapse risk if they are not treated with disease modifying therapy (DMT), new research suggests.

In a cohort study of women undergoing ART, those who did not receive DMTs had a significantly higher relapse risk than their peers who were treated with the drugs.

In addition, the likelihood of achieving pregnancy through ART while having MS appeared favorable, researchers note.

“In this modern case series and the largest cohort to date, we identified a lower risk of relapses after ART than previously reported,” Edith L. Graham, MD, assistant professor, Department of Neurology, Northwestern University, Chicago, Illinois, and colleagues  write.

“Importantly, continuing DMT during ART may reduce risk of relapse during this period of marked hormonal fluctuations and stressors,” they add.

The findings were presented here at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022.

Study Details

Previous research shows a wide range of relapse risk in patients with MS undergoing ART.

To investigate the potential role of DMTs in mitigating relapse risk, the researchers evaluated data on 37 women with either relapsing-remitting MS (n = 31) or clinically isolated syndrome (CIS; n = 6) who underwent ART.

The women all had low disability, with a median Expanded Disability Status Scale (EDSS) score of 1.0.

All participants had undergone one to five cycles of reproductive therapy between 2010 and 2021.

Most (78%) were receiving ART because of infertility or a need for pre-implantation genetic testing, whereas 22% were undergoing the treatment for the preservation of fertility. Average age of the participants was 35 years and average disease duration was 7.4 years.

Among 19 of the 37 patients who were taking DMTs prior to ART, 10 remained on the medication throughout ovarian hyperstimulation.

In those who received DMTs in the 12 months prior to ART, treatment included glatiramer acetate (n = 9), interferons (n = 3), and dimethyl fumarate (n = 1). Three participants received B-cell depleting agents.

In addition, three women received medication in response to a rebound after discontinuation. Of these, two received fingolimod (Gilenya) and one natalizumab (Tysabri).

Five patients (13.5%) experienced MS relapses in the 12 months following ART therapy. Among those experiencing relapse, none were treated with DMTs during the preceding 12 months.

Of the relapses, three occurred within 3 months of the ART treatment, one within 6 months, and one within 12 months.

High Rate of Successful Pregnancy

Overall, 24 of 29 women (83%) underwent in vitro fertilization (IVF) with embryo transfer as part of ART achieved pregnancy. The remaining 5 patients were undergoing egg cryopreservation.

Although 14 of the 24 who achieved pregnancy were on DMTs and 2 of 5 who did not achieve pregnancy were on the therapies, Graham noted, “these numbers seem too small to draw conclusions.”

In particular, patients may benefit from treatment with rituximab (Rituxan) or ocrelizumab (Ocrevus) 3 to 6 months prior to ART, “which gives better protection during ART cycle with low risk of fetal exposure,” she told Medscape Medical News.

“Treatment does not need to be discontinued if undergoing embryo banking only,” Graham added. “The risk to the fetus occurs only after embryo transfer.”

Although there is a lack of research examining whether MS relapse lowers the chance of pregnancy, Graham noted, “in theory, relapsing MS may compromise ART success because [patients] may have a narrower window to undergo ART treatments if they are trying to mitigate DMT exposure to the fetus.” 

However, the study’s results generally suggest favorable outcomes with ART among women with MS, she added.

“We found that overall, ART is actually very successful among people with MS. I was actually very surprised by this high rate of successful pregnancy,” Graham said.

She noted that as women with MS increasingly undergo IVF as well as egg cryopreservation, research on these issues is gaining importance for clinicians.

“This is going to be something that MS specialists need to know more about, particularly the safety of ART in their patients,” said Graham.

“What’s important is there are no [formal] recommendations along these lines, so this represents an opportunity to get the word out to clinicians that you want to make sure patients with MS are protected throughout the ART cycle and that you’re not discontinuing their DMT too early,” she added.

Protective Against Relapse?

Commenting on the study for Medscape Medical News, Jiwon Oh, MD, PhD, medical director of the Barlo Multiple Sclerosis Program at St. Michael’s Hospital, University of Toronto, Ontario, Canada, noted that while there are many guidelines/recommendations regarding use of older DMTs peri-pregnancy, data on many newer therapies is more limited.

“Often, when people do not have definitive evidence, they tend to take a conservative approach, which is why there is likely reluctance to keep patients on DMTs during ART as well as in early pregnancy,” said Oh, who was not involved in the research.

Importantly, there is also no definitive evidence of a relationship between MS relapses and ART success or pregnancy outcomes, she noted. However, “from a common-sense perspective, most clinicians worry that extreme stress or disability may negatively affect both ART and pregnancy outcomes,” she added.

Oh agreed that ocrelizumab is an appropriate choice in terms of preventing relapse during ART.

“Ocrevus is one of our highest-efficacy DMTs and is only dosed every 6 months. So this allows for ART cycles and conception without worrying about fetal drug exposure and the drug affecting ART cycles,” she said.

She noted the study’s findings “are in keeping with some prior studies, but not others, demonstrating there may be a higher risk of relapse with ART” in patients who are not taking a DMT.

“However, in my mind the most important conclusion from this study is that being on a DMT seems to be protective of relapse risk, which is an important point that will be useful to provide patients with clinical guidance,” Oh said.

Graham reported having received consulting fees from Genentech. Oh reported having received consulting or speaking fees from Alexion, Biogen Idec, BMS, EMD Serono , Genzyme, Novartis, and Roche.

Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022: Abstract P411. Presented February 25, 2022.

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