IL-17A Inhibitors Appear Effective in Treating AS, But Safety Needs Further Study
Medications that block the activity of the pro-inflammatory molecule interleukin-17A (IL-17A) can ease symptoms of ankylosing spondylitis (AS), but further research is needed to evaluate their safety, according to an analysis.
These findings were in the study “Efficacy and safety of interleukin-17A inhibitors in patients with ankylosing spondylitis: a systematic review and meta-analysis of randomized controlled trials,” published in the journal Clinical Rheumatology.
AS is characterized by inflammation that affects the joints of the spine, leading to the disease’s symptoms. The overarching aim of AS treatments is to ease symptoms by lowering this inflammation.
Recently, IL-17A inhibitors have emerged as one class of medications to do this. IL-17A inhibitors include Cosentyx (secukinumab) and Taltz (ixekizumab), which are approved to treat AS in the U.S. and elsewhere. Investigational IL-17A blockers in the U.S. include bimekizumab and netakimab.
To better understand the efficacy and safety of these medications in the context of AS, a team of researchers in China conducted a meta-analysis. This type of analysis pools and analyzes data from previously published scientific studies. Because meta-analyses include data from multiple scientific sources, they have more statistical power than any individual study.
Specifically, researchers analyzed 10 randomized controlled clinical trials (RCTs) — studies where an IL-17A inhibitor was compared to a control group. Six of the studies looked at Cosentyx, two evaluated Taltz, and one each assessed bimekizumab and netakimab.
Collectively, the 10 studies involved 2,613 AS patients. Trial duration ranged from six to 16 weeks.
The main measurement of efficacy was 20% or 40% improvement according to the Assessment of SpondyloArthritis international Society (ASAS) criteria, referred to as ASAS20 and ASAS40. Not all of the studies were part of the efficacy analysis. Notably, ASAS criteria include pain, function, inflammation, and a patient global assessment.
Statistical analyses demonstrated that the likelihood of attaining ASAS20 was 2.58 times more likely when treatment with IL-17A inhibitor is given, compared with placebo. Similarly, attaining ASAS40 was 2.8 times more likely with IL-17A blocker treatment. Both differences were statistically significant — that is, they were mathematically unlikely to be due to random chance.
Additional analyses indicated that IL-17A blockers significantly increased the likelihood of an improvement on at least five of six domains measured under ASAS criteria (ASAS5/6, which also assesses spinal mobility and a biomarker of inflammation), and enhanced the likelihood of partial remission as assessed by ASAS.
Disease activity, measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), was significantly reduced with IL-17A treatment.
Subgroup analyses suggested that the efficacy findings were similar for each of the medications analyzed.
“Through pooling the data of 10 independent RCTs and comprehensively analyzing the ASAS20 response, ASAS40 response, ASAS5/6 response, and ASAS partial remission, we found that IL-17A inhibitors significantly alleviated the clinical signs and symptoms of AS,” the researchers wrote.
In terms of safety, IL-17A inhibitor treatment was associated with a significantly greater likelihood of side effects, by about 23%. The risk of adverse events was also significantly higher with Taltz than with Cosentyx.
The most common side effects across studies was nasopharyngitis (the common cold), which was significantly more common with Cosentyx than Taltz.
Infection risk also significantly rose — roughly two times — with IL-17A inhibitor treatment. The risk of serious infections, however, was not significantly higher treatment compared with placebo groups. Substantial heterogeneity (study-to-study variation) in terms of infection outcomes was evident, the researchers said.
IL-17A inhibitor use did not significantly affect the risk of serious adverse events. Three deaths reported among all the included studies, but because data were limited, the team could not assess the effect of treatment on a risk of death.
“Studies with larger sample size and longer follow-up times are firmly warranted to evaluate the safety of IL-17A inhibitors in AS,” the researchers wrote.
Ongoing clinical trials and extension studies are continuing to evaluate the efficacy and safety of various IL-17A inhibitors, including Cosentyx, netakimab, and bimekizumab, they added.
“We will pay close attention to the progress of these studies in the future,” the scientists wrote.