Assessment of Infection Risk in Patients with Multiple Sclerosis Treated with Various DMDs
Although the increased risk of infections with some disease-modifying drugs (DMDs) is known, we still lack sufficient real-world clinical data to evaluate and compare the risk levels of individual drugs. A Swedish study therefore provides information about these risks with glatiramer acetate, beta interferon, natalizumab, fingolimod, and rituximab in the treatment of multiple sclerosis (MS).
Infections in MS Patients
It is known that patients with multiple sclerosis have a higher risk of developing infections than the general population, regardless of treatment. Studies available indicate that first-generation DMDs (beta interferon and glatiramer acetate) do not further increase this risk, while the use of second-generation DMDs (natalizumab and fingolimod) is associated with a higher risk of infection. For instance, natalizumab increases the risk of progressive multifocal leukoencephalopathy (PML). The risk of herpes zoster infection is particularly increased with fingolimod therapy.
Data from the Swedish National Registry
The Swedish cohort study included patients with relapsing-remitting MS who started therapy with beta interferon, glatiramer acetate, fingolimod, natalizumab, or rituximab from early 2011 to the end of 2017 and were followed in the national registry (rituximab is often used off-label for MS in Sweden). Each patient was matched with five controls of the same age, gender, and residence without a diagnosis of multiple sclerosis.
A total of 6421 patients were included in the study; some were treated with multiple drugs during the study period, resulting in a total of 8600 treatment episodes.
The time to occurrence of a serious infection (defined as an infection that becomes the main reason for hospitalization) and the incidence of infections requiring systemic antibiotics or antivirals were evaluated.
Incidence of Infections with Individual Drugs
Before statistical adjustments for potential confounding factors, the incidence of serious infections in patients treated with interferon and glatiramer acetate per 1000 patient-years was higher than in the general population: 8.9 (95% confidence interval [CI] 6.4–12.1) vs. 5.2 (95% CI 4.8–5.5). The incidence was even higher in patients treated with natalizumab (11.4; 95% CI 8.3–15.3), fingolimod (14.3; 95% CI 10.8–18.5), and rituximab (19.7; 95% CI 16.4–23.5).
After adjusting for all considered confounding factors (age, gender, country of origin, education, personal history, disease course), only the difference between first-line treatment and rituximab remained significant (hazard ratio [HR] 1.70; 95% CI 1.11–2.61).
Antibiotic treatment was most frequently used with rituximab and natalizumab, while it was indicated 15–18% less often with other drugs. Conversely, antivirals for herpes infections were used more with natalizumab (HR 1.71; 95% CI 1.27–2.32) and fingolimod (HR 1.82; 95% CI 1.34–2.46) than with rituximab, glatiramer acetate, and interferon.
There were 2 cases of PML recorded: 1 in a patient treated with fingolimod and 1 with rituximab. In both cases, treatment with natalizumab was discontinued < 6 months before the PML diagnosis. No infection-related deaths were reported in the study.
Conclusion
The study confirmed the previously known fact that the incidence of infections is higher in patients with MS than in the general population, with the difference being more pronounced for infections requiring hospitalization. The incidence of infections was lowest in patients treated with first-generation DMDs. The use of rituximab was associated with the highest incidence of serious infections.
(pab)
Source: Luna G., Alping P., Burman J. et al. Infection risks among patients with multiple sclerosis treated with fingolimod, natalizumab, rituximab, and injectable therapies. JAMA Neurol 2019 Oct 7, doi: 10.1001/jamaneurol.2019.3365 [Epub ahead of print].
Did you like this article? Would you like to comment on it? Write to us. We are interested in your opinion. We will not publish it, but we will gladly answer you.