Novel Interleukin Inhibitors Efficacious for Psoriatic Arthritis

Inhibitors of interleukin-6 (IL-6; clazakizumab), IL-12/23 (ustekinumab), and IL-17A (secukinumab, brodalumab, and ixekizumab) were shown to be effective and generally well tolerated for the treatment of psoriatic arthritis (PsA) in a systematic review and meta-analysis published in the Journal of Clinical Rheumatology.

A literature search was conducted that included randomized controlled trials designed to assess the efficacy of IL inhibitors using reported American College of Rheumatology 20 (ACR20; 20% improvement in PsA) response at 24 weeks. A total of 8 studies involving 2722 individuals demonstrated the efficacy of the IL inhibitors clazakizumab, ustekinumab, secukinumab, brodalumab, and ixekizumab for the treatment of patients with PsA.

Overall, 1896 participants were in the IL inhibitor group and 826 were in the placebo control group. ACR20, ACR50, and ACR70 risk ratios were 2.02 (95% CI, 1.65-2.47; P =.000), 2.95 (95% CI, 2.23-3.73; P =.00), and 5.14 (95% CI, 3.28-8.06; P <.00), respectively, in favor of active treatment vs placebo.

No evidence of significant heterogeneity among trials was observed. Subgroup analysis demonstrated efficacy in those patients who had never been treated with tumor necrosis factor and in those who did not respond or responded inadequately to treatment with tumor necrosis factor. The number of adverse events reported was higher in the treatment groups vs placebo groups, with the majority of events mild in intensity and not requiring any treatment adjustment (risk ratio, 1.17; 95% CI, 1.06-1.28; P =.001). No significant differences in drug withdrawals were reported among groups.

The investigators concluded that this study demonstrates the efficacy and tolerability of IL-6, IL-12, IL-17, and IL-23 for the management of PsA. “Although there are no head-to-head comparisons, the response rate to these IL inhibitors is similar to that previously reported with TNF-α inhibitors,” they concluded, adding, “The results of subgroup analyses should be tested in well-designed randomized controlled trials.”

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Reference

Bilal J, Riaz IB, Kamal MU, Elyan M, Sudano D, Khan MA. A systematic review and meta-analysis of efficacy and safety of novel interleukin inhibitors in the management of psoriatic arthritis [published online September 19, 2017]. J Clin Rheumatol. doi: 10.1097/RHU.0000000000000583