Certain MS treatments tied to greater infection risk than others

In patients with relapsing-remitting multiple sclerosis (MS), certain disease-modifying therapies (DMTs) may be more associated with serious infections than others, according to an observational study from Sweden.

“[T]he risk of serious infections among patients with MS who were treated with rituximab was higher than among patients with MS who were taking natalizumab [or] fingolimod, and this increased even more in comparison with those taking interferon beta and glatiramer acetate,” said the researchers.

Study participants were 6,421 patients with relapsing-remitting MS who were treated with rituximab (n=3,260), natalizumab (n=1,588), fingolimod (n=1,535), or interferon beta or glatiramer acetate (GA; n=2,217) as listed in the Swedish MS register (mean age at treatment initiation 39 years, 71.9 percent female). Patients were treated with interferon beta or GA, fingolimod, natalizumab, or rituximab for a mean 2.1, 2.7, 2.5, and 2.0 years, respectively. The patients were age-, sex-, and region-matched with 42,645 individuals without MS from the general population (comparator cohort).

Patients with MS on interferon beta or GA had a higher risk of serious infections leading to hospitalization compared with the comparator cohort (incidence rate [IR], 8.9 vs 5.2 per 1,000 person-years). [JAMA Neurol 2019;doi:10.1001/jamaneurol.2019.3365]

The infection risk was further elevated among patients on rituximab (IR, 19.7 per 1,000 person-years), fingolimod (IR, 14.3 per 1,000 person-years), or natalizumab (IR, 11.4 per 1,000 person-years) compared with the comparator cohort.

The risk of serious infections was significantly higher among rituximab users compared with those on interferon beta or GA (adjusted hazard ratio [adjHR], 1.70, 95 percent confidence interval [CI], 1.11–2.61). The risk of serious infections with fingolimod (adjHR, 1.30) and natalizumab (adjHR, 1.12), while elevated, was not significantly higher than that with interferon beta or GA. Natalizumab users had a significantly reduced risk of infections compared with rituximab users (HR, 0.66, 95 percent CI, 0.45–0.97)

Compared with interferon beta or GA users, antibiotic use was higher in rituximab and natalizumab users (HR, 1.23 and HR, 1.15, respectively), while antibiotic use was 19 and 14 percent lower in interferon beta or GA, and fingolimod users, respectively, compared with rituximab users.

The risk of herpes infection, determined by the prescription of herpes antiviral drugs during MS treatment, was elevated among fingolimod (HR, 1.70) and natalizumab users (HR, 1.61) compared with rituximab users, and was comparable between rituximab and interferon beta or GA users. There were two incidents of progressive multifocal leukoencephalopathy (PML), one each in rituximab and fingolimod recipients, both of whom had switched from natalizumab within 6 months of PML diagnosis.

Previous research has shown that patients with MS have an elevated risk of infections compared with the general population, irrespective of treatment modality. [Eur J Neurol 2013;20:1153-1160] Additionally, certain newer treatments for MS have been associated with an increased risk of infections [Open Forum Infect Dis 2018;5:ofy174] as opposed to interferon beta and GA which have not. [Curr Neurol Neurosci Rep 2017;17:88]

“These data provide further support for previous reports that patients with MS are at a generally increased risk of infections, as well as some support for an increased risk of infections in high-efficacy DMTs compared with injectable therapies,” the researchers said. However, the study does not account for minor infections, and may have been affected by confounding due to lack of data on body mass index, and varicella vaccination and smoking status, they added.

Nonetheless, the findings should improve awareness among physicians and patients on the risks of infection with the various treatments for MS. Follow-up is warranted to determine the long-term risks associated with these treatments, the researchers concluded.