In patients with rheumatologic diseases, treatment with interleukin inhibitors may increase the risk of serious infections, opportunistic infections, and cancer, according to a systematic review and meta-analysis published in JAMA Network Open.

To investigate these risks, study authors searched various databases for clinical trials evaluating interleukin therapy vs placebo in patients with rheumatic diseases in which safety data were reported. They identified 74 studies that included 29,214 patients; treatments evaluated in these studies included tocilizumab (18 trials), secukinumab (15 trials), anakinra (8 trials), ixekizumab (6 trials), rilonacept (6 trials), sarilumab (4 trials), sirukumab (4 trials), ustekinumab (4 trials), brodalumab (3 trials), guselkumab (2 trials), clazakizumab (2 trials), canakinumab (1 trial), and olokizumab (1 trial).

Pooled analysis showed that treatment with interleukin inhibitors was associated with a higher risk of serious infections (infections resulting in hospitalization, use of antibiotics, or death) when compared with placebo (odds ratio [OR] 1.97; 95% CI, 1.58-2.44; P <.001; I2 = 0%; high certainty). Moreover, the risk of opportunistic infection was found to be increased with interleukin inhibitors vs placebo (OR 2.35; 95% CI, 1.09-5.05; P =.03; I2 = 0%; moderate certainty).

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In addition, study data showed an increased risk of cancer in patients with rheumatologic diseases treated with interleukin inhibitors (OR 1.52; 95% CI, 1.05-2.19; P =.03; I2 = 11%; moderate certainty). “The findings in our study suggest that the risk of cancer may be increased with longer [interleukin] inhibitor therapy,” the study authors added.

Based on their findings, the authors concluded that infection risk with interleukin inhibitors appears to be comparable to what has been observed with other biologic therapies (ie, tumor necrosis factor inhibitors), while real-world data are needed to confirm the potential for increased cancer risk with long-term therapy.

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