A retrospective cohort study has revealed varying infection risks among disease-modifying therapies for multiple sclerosis, with notable findings on fumarates and anti-CD20 medications.

In the study, conducted at Yale University and published in Multiple Sclerosis and Related Disorders, investigators analyzed real-world infection data over a period of 8 years. In the retrospective, single-center study, Clare McGarvey Lambert, of the Department of Neurology at Yale New Haven Hospital, and her colleagues evaluated adult patients with multiple sclerosis (MS) treated with natalizumab, fumarates, S1P modulators, or anti-CD20 medications for more than 2 years between January 2013 and April 2021. Severe infections were identified as those requiring hospitalization, whereas mild infections were determined through outpatient antibiotic prescriptions or documentation of infection in medical charts.

Among the 473 patients with MS, infection risks differed based on the type and duration of disease-modifying therapy (DMT) use:

• Natalizumab: Patients receiving natalizumab (n = 104) showed no significant increase in severe or mild infection rates over prolonged use. The investigators noted that natalizumab appeared to be safe over extended use.
• Anti-CD20 medications: Patients receiving anti-CD20 therapies (n = 291) experienced an increased rate of mild infections correlated with treatment duration.
• Fumarates: Among patients taking fumarates (n = 61), severe infections requiring hospitalization were more common. This may reflect the baseline demographics of patients clinically selected to take this medication, which has historically been viewed as benign.
• S1P modulators: Data on patients taking S1P modulators (n = 17) was limited, but no statistically significant differences in infection rates were observed.

The investigators also identified predictors of infection risk. For mild infections, the rates were higher among patients with longer DMT use or those requiring a walking aid. Meanwhile, for severe infections, patients with progressive MS or long-term fumarate use were at increased risk, even after adjusting for confounders such as age, body mass index, and comorbidities.

"This paper endeavored to identify the real-world risk of long-term DMT use. We observed some expected and unexpected patterns in our cohort, but overall, there was low incidence of both mild and severe infections," the study authors indicated. 

The investigators utilized a zero-inflated negative binomial regression to assess the impact of treatment duration, patient characteristics, and therapy choice on infection rates.

The findings underscored the importance of considering both patient characteristics and DMT choice in assessing infection risks. While natalizumab was associated with low infection risks over extended periods, the investigators highlighted the need for closer monitoring of patients on fumarates or long-term anti-CD20 therapies.

It also provided valuable real-world data on the infection risks associated with commonly used DMTs in MS. Through differential risks based on drug type and duration, it offered insights that may guide personalized treatment decisions and risk management among patients with MS.

No conflict of interests were mentioned in the study.