IL-6, JAK inhibitors, rituximab increase severe infection risk in inflammatory arthritis
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WASHINGTON — Patients with inflammatory arthritis who receive rituximab, interleukin-6 inhibition or Janus kinase inhibitors demonstrate higher severe infection risks vs. TNF inhibitors, according to data presented at ACR Convergence 2024.
“This study was prompted by the need to better understand the risks for severe infections associated with different biologic and targeted synthetic disease-modifying antirheumatic drugs used for treating inflammatory arthritis,” Kasra Moolooghy, MD, MSc, of Arthritis Research Canada and the University of British Columbia, told Healio. “While biologic therapies have transformed inflammatory arthritis treatment by controlling inflammation, concerns remain about their potential side effects, particularly the risk of severe infections.”
Moolooghy added that the growing number of biologic therapies available for inflammatory arthritis can complicate the treatment process.
“Knowing whether the risk of side effects, like infections, differs between them will help patients and physicians make decisions about which agent to choose,” he said.
To compare severe infection risks among the various classes of biologic and targeted synthetic DMARDs in inflammatory arthritis, Moolooghy and colleagues conducted a population-based cohort study of administrative health data from Canada’s universal health care system. Eligible patients started treatment between January 1996 and December 2021 for rheumatoid arthritis, psoriasis, psoriatic arthritis or ankylosing spondylitis, and were followed until December 2022. The number of infections requiring hospitalization served as the primary endpoint.
“Given that previous studies have mostly focused on specific drugs rather than comparing all biologic or traditional synthetic DMARD classes in the same sample, there is limited evidence on the risk differences across these classes, especially outside of anti-TNF agents,” Moolooghy said. “The study aimed to fill this gap by providing real-world data from a large population sample, with long follow-up periods, to better inform patients and health care providers about these risks across different treatment options.”
The final analysis included data for 24,005 patients who had been followed for a mean duration of 6.2 years (standard deviation, 5) after initiating DMARD therapy.
Overall, 54,803 treatment courses underwent analysis, with 59% of those for RA, 26% for PsA and 15% for ankylosing spondylitis. The mean duration of treatment was 2.7 years (SD, 3.2).
According to the researchers, the 1-year risk for severe infections was significantly higher with IL-6 inhibition (aRR = 1.52; P < .01) and rituximab (Rituxan, Genentech) (aRR = 1.36; P < .01), compared with TNF inhibition.
At 5 years, infection risk was highest with JAK inhibition (aRR = 1.38; P < .01), followed by IL-6 inhibition and rituximab. A similar trend persisted through 10 years, according to the researchers.
“This risk was notable across different follow-up periods of 1, 5, and 10 years, indicating that the risk persists over time,” Moolooghy said. “The magnitude of the increased risk, however, was quite small.”
No differences in infection risk were observed for abatacept (Orencia, Bristol Myers Squibb), IL-17 inhibition or IL-23 inhibition, compared with the TNF inhibitors.
Moolooghy suggested that, despite adjustments, residual confounding and channeling bias may persist.
“There are more nuances when interpreting the results, especially when delving deeper into subgroup analyses,” he said. “For instance, when only considering biologic or traditional synthetic DMARD use for the treatment of RA, only treatment with rituximab was associated with an increased risk for infection, relative to anti-TNF, and not anti-IL6 or JAK inhibition. Treatment with anti-IL-23 for psoriatic diseases was associated with a lower risk of infection.”
Despite these nuances, there is much to be learned from these findings, according to Moolooghy.
“Infection risk varies among different classes of biologic or traditional synthetic DMARDs for inflammatory arthritis,” he said. “This real-world evidence emphasizes the importance of considering patient-specific risk factors, such as age and comorbidities, when selecting treatments, especially for those at higher infection risk. Ultimately, these findings can help inform individualized treatment decisions when weighing the risks and benefits of different medications.”
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Moolooghy K. Abstract #1716. Presented at: ACR Convergence 2024; Nov. 14-19, 2024; Washington, D.C.
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