Study Assesses Risk of Infections, Cancer With Interleukin Inhibitors in Rheumatic Disease

It is currently uncertain to what extent interleukin inhibitors may increase the risk of serious infections and cancer in patients being treated for rheumatic diseases.

Patients with rheumatologic diseases treated with interleukin (IL) inhibitors may be at an increased risk of serious infection, opportunistic infections, and cancer, according to a new study published in JAMA Network Open.

According to the study, the risks may be comparable to those reported for other biologics approved for the treatment of rheumatic diseases.

A number of IL-1, IL-6, IL-12/23, and IL-17 inhibitors are used as therapy options in rheumatologic diseases. Although IL inhibitors have demonstrated efficacy, there are limited data regarding their safety profile and it is unknown to what extent IL inhibitors may increase the risk of serious infections and cancer.

To assess this risk, researchers conducted a systematic review and meta-analysis using data from clinical trials that evaluated IL inhibitor therapies and reported safety data. The meta-analysis included 74 studies including 29,214 patients. The studies included tocilizumab, secukinumab, anakinra, ixekizumab, rilonacept, sarilumab, sirukumab, ustekinumab, brodalumab, guselkumab, clazakizumab, canakizumab, and olokizumab.

Diseases in the study included rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis, gout, juvenile idiopathic arthritis, giant call arteritis, systemic lupus erythematosus, primary Sjogren syndrome, systemic sclerosis, familial Mediterranean fever, and osteoarthritis.

Overall, 69 studies included data for serious infections across all rheumatic diseases, comprising a total of 24,236 patients. The pooled analysis showed an increased risk of serious infections with the use of IL inhibitors compared with placebo.

Fourteen of the studies reported the incidence of opportunistic infection, with 9998 patients in these trials. Oral candidiasis was the most commonly reported opportunistic infection, according to the analysis. Others included herpes zoster, esophageal candidiasis, Mycobacterium tuberculosis, atypical mycobacterial infections, and histoplasmosis. Overall, the results showed an increased risk of opportunistic infections with the use of IL inhibitors compared with placebo.

A total of 46 studies with approximately 21,000 patients had data on the incidence and type of cancers across all rheumatic diseases. A total of 141 cases of cancer reported in the treatment groups and 28 in the control groups. The analysis found that, overall, there was an increased risk for cancer with IL inhibitors compared with placebo.

The researchers noted that, although the review suggest that the risk of cancer may be increased with longer IL inhibitor therapy, the results are not conclusive and should be further investigated by long-term data.

“This analysis provides estimates of toxic effects for infections and cancer associated with the use of IL inhibitors that can inform shared decision-making when patients and clinicians are contemplating the use of IL inhibitors for rheumatologic diseases,” they concluded.


Bilal J, Berlinberg A, Riaz IB, et al. Risk of infections and cancer in patients with rheumatologic diseases receiving interleukin inhibitors: a systematic review and meta-analysis. JAMA Network Open. 2019. Doi: 10.1001/jamanetworkopen.2019.13102.

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