Women with multiple sclerosis (MS) taking b-cell suppressing therapies are at risk of developing persistent inflammatory vaginitis (IV), according to a multidisciplinary team of clinicians from NewYork-Presbyterian/
“The goal is to establish and describe this condition more thoroughly and create an awareness of it,” says co-study author Hoosna Haque, MD, an obstetrician-gynecologist at NewYork-Presbyterian/
A Treatment Revolution
B-cell depleting therapies (rituximab, ocrelizumab, ofatumumab, ublituximab) have proven to be invaluable in the treatment of MS. Clinicians have used anti-CD20 monoclonal antibodies off- label for more than two decades, and the first B cell depleting therapy for MS, ocrelizumab, was approved in 2017. Since then, use has skyrocketed.
The goal is to establish and describe this condition a bit more and create awareness of it. Any type of autoimmune condition affects women disproportionately, and we have these amazing therapies available. But we want to identify any potential risks, diagnose them early, and manage them.
— Dr. Hoosna Haque
“The number of individuals receiving B-cell depleting therapy for MS exponentially increased about seven years ago,” says Claire Riley, MD, a neurologist and Co-Director of the Multiple Sclerosis Center at NewYork-Presbyterian/
Among the four case studies, ages ranged from 27 to 41. All patients presented with unusual vaginal discharge, irritation, pain (including dyspareunia), and/or itching. Three patients were treated with rituximab and the fourth with ocrelizumab.
Conventional approaches to treating patients’ IV, including hydrocortisone and antibiotics, were mostly unsuccessful. Discontinuing the b-cell depleting therapy led to a partial or complete improvement in vaginal health, implying an association.
Sorting Out A Vexing Side Effect
The team is now focused on probing the link between treatment and IV as well as trying to quantify it.
“We use a lot of agents to modify the immune system in MS, and of course, our patients have an autoimmune disease, and so they may be more likely to develop dysregulated immune responses across the board,” says Dr. Riley.
Determining the incidence of B-cell-associated IV in MS is hindered by the lack of a specific diagnostic code, which prevents easy comparisons between MS patients with inflammatory
vaginitis who are on B-cell therapies and those who aren’t within a data set. “That would be a straightforward dive into claims data if we only had a diagnostic code,” Dr. Riley says.
Finding Solutions
Answering other questions could lead to ways to prevent or reduce the unwanted side effect. “One of the things that we are trying to do with this paper is to get neurologists asking, ‘Is this happening with all B-cell therapies?’” says study first author Libby Levine, NP, a multiple sclerosis nurse practitioner at the Multiple Sclerosis Center at NewYork-Presbyterian/
Maybe there are things that we do to mitigate this risk. Anti-CD20 is a very effective drug class for multiple sclerosis. I don't want to take it off the table for young women who might otherwise do very well with it.
— Dr. Claire Riley
The team also wants to investigate whether IV is strictly limited to B-cell depletion. “Other agents also might be triggers,” Dr. Riley says. “I'm interested to know if there are characteristic changes in the vaginal microbiome, the bacteria that live and thrive in the vaginal environment, with these different agents. And maybe there are things that we can do to mitigate the risk of IV with immunotherapy. Anti-CD20 is a very effective drug class for multiple sclerosis. I don't want to take it off the table for young women who might otherwise do very well with it.”
Creating Awareness
The report is intended to alert clinicians in neurology and other medical specialties to the possible problem for female MS patients. “The goal is to put this on the radar of clinicians who are treating women with multiple sclerosis,” says Dr. Riley.
That’s particularly important due to the stigma surrounding female reproductive health. “Patients are probably not going to think to bring up vaginal symptoms and painful sex with their neurologist or even primary care,” adds Dr. Haque. “We want to take people out of their silos and get clinicians used to the idea of asking about these symptoms and patients used to speaking about them, because this is an important component of well-being and there's often a big hesitation.”
Adds Dr. Riley, “I try to pass this along to our fellows and trainees that we need to provide an open and accepting environment where patients feel comfortable talking about anything.”
The Benefits of Cross-Disciplinary Care
At NewYork-Presbyterian, a culture of collaboration among providers is present across the system. “With the patient who originally brought this side effect to our attention, we were collaborating with people across NewYork-Presbyterian, Columbia, and Weill Cornell Medicine— pathology, dermatology, rheumatology, and obstetrics and gynecology,” says NP Levine. “The vastness of our network makes it easy for us to put our heads together and come up with a way to get the word out and hopefully quantify the prevalence of this down the line.”
Dr. Riley notes that ties with obstetrics and gynecology were significant even before this issue emerged, as MS is a disease that disproportionately affects women, particularly of childbearing age.
“We have a lot of conversations about family planning and about how to get women where they want to be safely,” she says. “Relationships like the one that we've developed with Dr. Haque and the team in gynecology are really key to our success in creating a comprehensive care model for our patients.”
