Interleukin inhibitors linked to elevated infection, cancer risk
medwireNews: Results of a meta-analysis suggest that treatment with interleukin (IL) inhibitors may be associated with an increased risk for infections and cancer among people with rheumatic diseases.
These findings “can inform shared decision-making when patients and clinicians are contemplating the use of interleukin inhibitors,” say Jawad Bilal (University of Arizona, Tucson, USA) and co-authors.
The meta-analysis, reported in JAMA Network Open, included 74 randomized controlled trials of IL inhibitors comprising a total of 29,214 participants with rheumatic diseases. Rheumatoid arthritis (RA) was the most common indication for IL inhibitors, with 35 trials for RA in the meta-analysis, followed by psoriatic arthritis (n=12 trials), ankylosing spondylitis (n=9), gout (n=5), and juvenile idiopathic arthritis (n=5).
The most frequently investigated agent was the IL-6 receptor inhibitor tocilizumab – tested in 18 trials – while there were 15 trials for the IL-17A inhibitor secukinumab, eight for the IL-1 receptor inhibitor anakinra, and six each for the IL-17A inhibitor ixekizumab and the IL-1 inhibitor rilonacept.
In the 69 trials with available data, 486 cases of serious infection occurred among 17,177 patients treated with an IL inhibitor during a median follow-up of 24 weeks, compared with 96 cases among 7059 individuals given placebo, translating into a significantly higher risk in the active treatment group (odds ratio [OR]=1.97).
IL inhibitors were also associated with an increased risk for opportunistic infection over a median follow-up of 54 weeks, with 43 events occurring in 7153 people treated with IL inhibitors in 14 trials, and five events occurring in 2845 people given placebo, giving a significant OR of 2.35.
And in the analysis of cancer incidence, involving 45 studies with 15,244 patients given an IL inhibitor and 5821 given placebo, 141 cases of cancer occurred during a median of 28 weeks in the active treatment group compared with just 28 cases in the placebo group, giving a significant OR of 1.52.
These findings equate to numbers needed to harm of 67 for one additional serious infection over 24 weeks, 250 for one additional opportunistic infection over 54 weeks, and 250 for one additional case of cancer over 28 weeks, explain Bilal and colleagues.
The researchers also found that the duration of IL inhibitor use was significantly associated with cancer risk (correlation coefficient=0.012 for each 1-week increase in drug use), but note that “the short duration of follow-up in studies included in this review may not be sufficient to detect the actual cancer risk, which can take years to develop.”
Nevertheless, they say that the possibility of increased cancer risk with long-term IL inhibitor use “should be taken into consideration and needs to be confirmed by real-world data, such as long-term epidemiologic studies from registries.”
There was no significant association between duration of treatment and serious or opportunistic infection risk.
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