Risk of Serious Infection for Patients With MS Varies Depending on Treatment

Patients with multiple sclerosis (MS) have a higher risk in general of infections, but the risk varies depending on their treatment, according to a new study in JAMA Neurology.

While new disease-modifying therapies (DMTs) to treat MS have different modes of action, they all interact with the patient’s immune response, which has raised concerns about an increased susceptibility to infections, among other adverse events.

While there is no evidence that first-generation, injectable DMTs increase the risk of infection, “…the second-generation, so-called high-efficacy DMTs, including natalizumab and fingolimod, have been associated with increased risk of infections compared with placebo or interferon beta and glatiramer acetate in randomized clinical trials and postmarketing surveillance,” the authors explained.

The researchers analyzed data from a nationwide register-based cohort in Sweden. A total of 6421 patients with MS were included, as was a comparator cohort of 42,645 individuals. The patients with MS had started treated with interferon β and glatiramer acetate, fingolimod, natalizumab, or rituximab between January 1, 2011, and December 31, 2017. The registry used covers approximately 80% of all patients with MS in Sweden.

There were a total of 8600 treatment episodes for the MS cohort. There were 2217 initiations of interferon β and glatiramer acetate, 1535 of fingolimod, 1588 of natalizumab, and 3260 of rituximab. The mean age of patients starting treatment was mostly similar (38.8 years) with the exception of natalizumab, which had a slightly younger mean age (35.0 years).

Patients starting interferon β and glatiramer acetate had lower MS disability based on the Multiple Sclerosis Impact Scale psychological score and the Expanded Disability Status Scale. In comparison, patients initializing on natalizumab tended to have higher disability.

The incidence rate of serious infections among patients treated with interferon β and glatiramer acetate (incidence rate, 8.9 [95% CI, 6.4-12.1] per 1000 person-years) was similar to the rate for patients treated with natalizumab (11.4 [95% CI, 8.3-15.3] per 1000 person-years), and both were lower than the rate among patients treated with fingolimod (14.3 [95% CI, 10.8-18.5] per 1000 person-years) or rituximab (19.7 [95% CI, 16.4-23.5] per 1000 person-years).

However, these findings were confounded by age. After adjusting, only the difference between interferon β and glatiramer acetate and rituximab remained statistically significant (hazard ratio, 1.70 [95% CI, 1.11-2.61]). Patients with MS on rituximab had the highest rate of antibiotic use, followed by natalizumab and fingolimod, and interferon β and glatiramer acetate. Rates of antibiotic use for patients with MS was higher than the general population.

The authors noted that the results for rituximab were in line with studies of the drug to treat rheumatoid arthritis.

“These findings should be considered in the risk-benefit assessment of MS therapies, and further monitoring is important to better assess long-term risks,” the authors concluded.

Reference

Luna G, Alping P, Burman J, et al. Infection risks among patients with multiple sclerosis treated with fingolimod, natalizumab, rituximab, and injectable therapies [published online October 07, 2019]. JAMA Neurol. doi:10.1001/jamaneurol.2019.3365.