The risk of respiratory tract infections and interstitial lung disease with interleukin 12/23 and interleukin 23 antagonists in patients with autoimmune diseases: A systematic review and meta-analysis

Background: Respiratory tract infections (RTIs) and interstitial lung disease (ILD) secondary to interleukin (IL) 12/23 or IL-23 antagonists have been reported in autoimmune diseases. Objective: To assess the risk of RTIs and noninfectious ILD with these drugs. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials. Risk of RTIs and noninfectious ILD was compared to placebo by Mantel-Haenszel risk difference. We divided RTIs into upper RTIs (URTI), viral URTIs, and lower RTIs (LRTIs) including infectious pneumonia. Noninfectious ILD included ILD, eosinophilic pneumonia, and pneumonitis. Results: We identified 54 randomized controlled trials including 10,907 patients with 6 IL-12/23 or IL-23 antagonists and 5175 patients with placebo. These drugs significantly increased the risk of RTIs (MantelHaenszel risk difference, 0.019; 95% confidence interval, 0.005-0.033; P =.007), which was attributed to URTIs, but not viral URTIs or LRTIs. There was no significant difference in infectious pneumonia and noninfectious ILD between 2 groups. Limitations: Because of the rarity of infectious pneumonia and ILD, sensitivity analysis was required. Conclusions: The use of IL-12/23 or IL-23 antagonists for autoimmune diseases increased the risk of URTIs, but not viral URTIs, LRTIs, and noninfectious ILD.