Interleukin (IL) therapy for the treatment of rheumatologic diseases may increase the risk for serious infections, opportunistic infections, and cancer, according to a review published in JAMA Network Open.
Several ILs have been targeted as treatment modalities for immunologic diseases, including psoriasis, rheumatoid arthritis, psoriatic arthritis, and inflammatory bowel syndrome, because of their central role in inflammation and immune regulation. ILs have an integral role in regulation and inflammation of the immune system by promoting proliferation, activation, migration, and regulation of leukocytes.
Through several well-established clinical trials, the efficacy of targeted biologics has been well supported; however, the safety profile of these agents is not as clear. The increased risk for infections with biologics and IL inhibitors has been a safety concern, as has the blockage of biologic pathways leading to immune dysregulation. Although the use of IL therapy is widespread, the extent that this this therapy may be associated with an increased risk for serious infections and cancers is still unknown. Therefore, this review assessed the risk for serious infections, opportunistic infections, and cancer in patients with rheumatologic disease treated with IL inhibitors.
In total, 74 randomized, placebo-controlled trials that evaluated IL inhibitor therapies in rheumatic disease were extracted from published clinical trial databases and included in the analyses. Within the included 74 trials, a total of 29,214 patients with rheumatologic diseases such as rheumatoid arthritis, ankylosing spondylitis, and gout, among others, were included: 24,236 patients with serious infections, 9998 patients with opportunistic infections, and 21,065 patients with cancer. Study data were extracted by 2 independent investigators who also assessed the risk for bias and certainty. The outcomes of interest included the number of serious infections, opportunistic infections, and cancers in patients receiving IL therapies compared with placebo. To measure this, fixed effects meta-analysis was conducted and odds ratios (ORs) were pooled for incidence of infections and cancers in the IL therapy population compared with placebo.
Results suggest that when compared with placebo, patients with rheumatologic diseases who are treated with IL inhibitors have an increased risk for serious infections (OR, 1.97; 95% CI, 1.58-2.44; P <.001; high certainty), opportunistic infections (OR, 2.35; 95% CI, 1.09-5.05; P =.03; moderate certainty), and cancers (OR, 1.52; 95% CI, 1.05-2.19; P =.03; moderate certainty). The results of sensitivity analyses without continuity correction demonstrated similar data regarding all 3 endpoints.
Overall, the review authors concluded that, “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.”