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June 25, 2020
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IL-17 inhibitors effective for ankylosing spondylitis, but boost infection risk

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Treatment with IL-17 inhibitors significantly increases response rates among patients with ankylosing spondylitis, but with an increased risk for non-severe infections, according to a meta-analysis published in Arthritis Research & Therapy.

“The emergence of interleukin (IL)-17 inhibitors has changed the treatment landscape of active ankylosing spondylitis,” Yufeng Yin, of the First Affiliated Hospital of Soochow University, in Suzhou, China, and colleagues wrote. “Clinical trials focusing on several other IL-17 inhibitors, including bimekizumab and netakimab, are underway to evaluate their therapeutic potential in ankylosing spondylitis. To date, a comprehensive overview of different IL-17 inhibitors as an entity in ankylosing spondylitis has not been satisfactorily explained.”

Treatment with IL-17 inhibitors significantly increases response rates among patients with ankylosing spondylitis, but with an increased risk for non-severe infections, according to a meta-analysis.

To analyze the efficacy and safety of IL-17 inhibitors among patients with ankylosing spondylitis, Yin and colleagues conducted a meta-analysis of six phase 3 trials identified through a systematic literature review. The trials were randomized, double-blind, placebo-controlled studies with a combined 1,733 participants. Among these patients with active ankylosing spondylitis, 1,153 received IL-17 inhibitors, including secukinumab (Cosentyx, Novartis) or ixekizumab (Taltz, Eli Lilly), while 580 patients received a placebo.

The primary endpoint was the proportion of patients demonstrating at least a 20% improvement in the Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16. The secondary endpoint was ASAS40 at week 16.

According to the researchers, participants treated with IL-17 inhibitors demonstrated a significant increase in ASAS20 (RR=1.63; 95% CI, 1.45-1.84) and ASAS40 (RR=2.12; 95% CI, 1.75-2.56) response rates at week 16, compared with those who received placebo. Investigators noted more treatment-emergent adverse events (RR=1.11; 95% CI, 1.01-1.22) and non-severe infections (RR=1.82; 95% CI, 1.4-2.37) following treatment with IL-17 inhibitors vs. placebo.

There was no increased risk for other adverse events in connection with IL-17 inhibitors, including death, discontinuation due to adverse events or serious adverse events.

“The findings of this meta-analysis suggest that IL-17 inhibitors are significantly effective in improving ASAS20/40 response rates at week 16 in patients with active ankylosing spondylitis,” Yin and colleagues wrote. “IL-17 inhibitors seem to be associated with higher ASAS20 response rates in TNFi-naive subjects than TNFi-IR subjects. Meanwhile, there is a higher incidence of infectious diseases attributable to IL-17 inhibitors than to placebo, with most infections being mild or moderate. IL-17 inhibitors can be considered a favorable option for patients with active ankylosing spondylitis, especially TNFi-IR subjects.”