Herpes Zoster Infection With MS Treatment Higher in Women?

Nancy A. Melville

June 04, 2020

Reports of herpes zoster virus (HZV) among patients being treated with disease-modifying therapies (DMTs) for multiple sclerosis (MS) are nearly 5 times higher among women vs men and commonly occur in people under the age of 40, a new study of adverse event reports on a variety of DMTs suggests.

DMTs are known to be associated with a potentially increased risk of opportunistic infections, including HZV. However, data are lacking on issues such as the relative frequency of HZV and the distribution of cases among age and gender groups, senior author Ahmed Z. Obeidat, MD, PhD, of the Medical College of Wisconsin, Milwaukee, told Medscape Medical News.

"In my practice, we noticed patients being treated with DMTs were developing shingles at much younger ages than would be typical, so we were interested in looking at the distribution of cases among people treated with DMTs," he said.

For the study, presented as part of the 2020 Virtual Annual Meeting of the Consortium of Multiple Sclerosis Centers, Obeidat, first author Nicola Carlisle, MD, also of the Medical College of Wisconsin, and their colleagues turned to data from the US Food and Drug Administration's (FDA) Adverse Event Reporting System.

They analyzed reports on adverse events involving HZV and varicella among patients with MS received between January 1999 and June 2019. The reports involved a range of MS DMTs, including interferon beta, glatiramer acetate, natalizumab, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, or ocrelizumab.

Recently approved DMTs including cladribine and siponimod were excluded due to an insufficient number of reports.

Among 3335 reports that were identified, they found highest mean annual report rates of HZV were for natalizumab, at 115.4, and lowest for glatiramer acetate, with just 5.3 reports.

The mean annual report rates for HZV among the other DMTs were ocrelizumab, 88.3; dimethyl fumarate, 73.4; fingolimod, 72.9; interferon beta, 32.9; alemtuzumab, 21.7; and teriflunomide, 13.9.

Overall, the reports of HZV were 4.5 times more common among females, ranging from 2.1 times greater with alemtuzumab to 11.4 times greater for females with interferon-beta.

The highest percentages of reports involved people in their 50s, with the exceptions of fingolimod, which had the highest rate of reports among patients in their 40s, and alemtuzumab, in which the highest percentage of reports involved patients in their 30s.

Meanwhile, as many as 25.7% of cases occurred in people under the age of 40 years, while 77.6% of total reports of HZV were in age groups between 31 years and 60 years.

"These rates are different than what is expected in the shingles population, which usually involves people over 60," Obeidat said.

He noted that while MS is known to affect more women than men, the fivefold increase in HZV well exceeds female-male ratio in MS, which is about 2.5 to 1.

Obeidat speculated that one factor explaining the higher reports of younger patients could be that fewer older patients are taking DMTs.

"Many of our patients with MS may not be treated with DMTs when they are older or they may be on older DMTs that don't have as much of a risk of opportunistic infections or activation, or some older patients may not be on medications anymore, so this may be why we are seeing this," he said.

In commenting on the study, Joshua Katz, MD, co-director of the Elliot Lewis Center for Multiple Sclerosis Care, Wellesley, Massachusetts, speculated that numerous factors could explain the higher rates of women developing HZV.

"One wonders, for instance, did pregnancy play a role, were some of the women on prior medications?" he told Medscape Medical News.

"So the statistical difference is interesting, but it's hard to see what the explanation could be."

While DMTs typically can be effective in suppressing an MS flare even if a patient develops shingles, the risks of the shingles, itself, is a concern, Katz added.

"Just about any infection that stimulates an inflammatory response has some risk of worsening symptoms with MS; however, the bigger risk is probably the shingles itself and getting post-herpetic neuralgia," he explained.

"Sometimes there can be independent neurological problems just from MS, and that's probably a bigger risk than worsening the MS," he said.

Clinicians should therefore keep shingles on their radar before starting patients on DMTs, Katz added.

"For many of the medications that are immunosuppressive, you want to check patients' baseline levels of antibodies for zoster and if they don't have antibodies, then you do want to vaccinate them."

He noted that the new HZV vaccine is not a live vaccine and has a high efficacy rate, "so we think we can safely administer it in most cases."

"A concern is whether some DMTs may render the vaccine less effective, and we are looking at studying that with ocrelizumab and maybe some other B-cell depleting treatments."

Obeidat's disclosed relationships with Alexion, Biogen, Bristol Myers Squibb, Celgene, EMD Serono, Genentech, Sanofi and Novartis. Katz has been a speaker for Biogen, Genetech, Sanofi and EMD Serono.

2020 Virtual Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC): Abstract DXT55. Published online June 1, 2020.

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