Small molecule tyrosine kinase inhibitors appear to increase the risk of nonopportunistic respiratory infections but not serious pulmonary adverse events, according to a systematic review and meta-analysis published online in the journal Rheumatology.
“As small molecule tyrosine kinase inhibitors are novel, long-term safety is uncertain,” researchers wrote. “Due to increasing use, characterization of their true adverse event profile is critical.”
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To investigate the pulmonary adverse event risk of small molecule tyrosine kinase inhibitors, researchers analyzed 47 randomized controlled trials, 25 observational studies, and seven post-marketing surveillance studies involving Janus kinase inhibitors or spleen tyrosine kinase inhibitors. Nearly 160,000 participants were involved.
Compared with placebo, small molecule tyrosine kinase inhibitors significantly increased the risk of upper respiratory tract infections (risk difference [RD] 0.03; 95% CI, 0.01, 0.05; based on 36 studies with 14,724 participants), lower respiratory tract infections (RD 0.01; 95% CI, 0.00, 0.02; based on 24 studies with 12,302 participants), influenza (RD 0.01; 95% CI, 0.00, 0.01; based on 22 studies with 10,684 participants), and pneumonia (RD 0.00; 95% CI, 0.00, 0.01; based on 33 studies with 15,511 participants), researchers reported.
However, the meta-analysis found no increased risk for other respiratory complications, including pulmonary embolism, with the use of small molecule tyrosine kinase inhibitors.
Khoo JK, Barnes H, Key S, Glaspole IN, Östör AJ. Pulmonary adverse events of small molecule JAK inhibitors in autoimmune disease: systematic review and meta-analysis [published ahead of print May 14, 2020]. Rheumatology. doi:10.1093/rheumatology/keaa117