Novel Inhibitors Appear to Raise Risk of Certain Respiratory Infections

Small molecule Janus kinase (JAK) inhibitors and spleen tyrosine kinase (SyK) inhibitors appear to increase the risk of nonopportunistic respiratory infections, according to results of a new systematic review and meta-analysis. 

The findings also show that the risk of serious pulmonary adverse events appears to be low.

“Small molecule tyrosine kinase inhibitors (smTKI) [comprising mostly JAK inhibitors and, to a lesser extent, SyK inhibitors] modulate the cytokine receptor-mediated intracellular signal cascade, and are an effective treatment for autoimmune diseases and malignancies,” the researchers wrote. “As smTKI are novel, long-term safety is uncertain. Due to increasing use, characterization of their true adverse event profile is critical.”

The systematic review and meta-analysis included 47 randomized controlled trials, 25 observational studies, and 7 post-marketing surveillance studies, which together comprised 159,652 participants.

The trials and studies were identified in the EMBASE, MEDLINE, CENTRAL, and Pneumotox database and had assessed the pulmonary and serious adverse effects of smTKIs among patients with autoimmune diseases. Among the included studies, the researchers had compared any smTKI with placebo or another therapy, or as monotherapy at different doses.

Compared with placebo, the researchers found that smTKI use significantly increased the risk of upper respiratory tract infections (based on evidence from 36 studies), lower respiratory tract infections (24 studies), influenza (22 studies), and pneumonia (33 studies). 

However, the analysis showed no increased risk of pulmonary embolism or other respiratory complications with smTKI use, the researchers reported.

“SmTKI increases the risk of non-opportunistic respiratory infections compared with placebo. The risk of any serious pulmonary adverse events is low,” the researchers concluded.

—Jolynn Tumolo

Reference:

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. Rheumatology (Oxford). 2020;59(9):2217-2225. doi:10.1093/rheumatology/keaa117