A Systematic Review and Meta-analysis of Efficacy and Safety of Novel Interleukin Inhibitors in the Management of Psoriatic Arthritis

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Abstract

Objective

The aim of this study was to systemically review the efficacy and safety of inhibitors of interleukin 6 (IL-6): clazakizumab, IL-12/23: ustekinumab, and IL-17A: secukinumab, brodalumab, and ixekizumab in psoriatic arthritis (PsA).

Methods

The literature search was conducted using MEDLINE, EMBASE, Cochrane Library, Scopus, and Web of Science. We included randomized controlled trials that assessed the efficacy of IL inhibitors and reported American College of Rheumatology 20 response at 24 weeks. Meta-analysis was done using random-effects model utilizing the DerSimonian and Laird method. Quality assessment was done using RobotReviewer Cochrane Risk-of-Bias Assessment Tool. Heterogeneity was assessed with Q statistic and quantified with I2. Publication bias was assessed with a funnel plot.

Results

Eight studies including 2722 subjects demonstrate the efficacy of IL inhibitors clazakizumab, secukinumab, ixekizumab, brodalumab, and ustekinumab in the treatment of PsA. The American College of Rheumatology 20/50/70 risk ratios were 2.02 (95% confidence interval [CI], 1.65–2.47; P = 0.000), 2.95 (95% CI, 2.32–3.73; P = 0.00), and 5.14 (95% CI, 3.28–8.06; P = 0.00), respectively, in favor of treatment versus placebo. There was no evidence of significant heterogeneity between trials. Subgroup analysis showed efficacy in patients who were tumor necrosis factor naive, as well as tumor necrosis factor nonresponders or inadequate responders. The number of adverse events was higher in the treatment groups versus placebo, the majority were mild and did not require treatment adjustment (risk ratio, 1.17; 95% CI, 1.06–1.28; P = 0.001). There was no significant difference in drug withdrawals.

Conclusions

Our meta-analysis shows that the inhibitors of IL-6 (clazakizumab), IL-12/23 (ustekinumab), and IL-17A (secukinumab, brodalumab, ixekizumab) are efficacious and generally well tolerated when used to treat patients with PsA.

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