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Meta-Analysis
. 2021 Mar;84(3):676-690.
doi: 10.1016/j.jaad.2020.08.026. Epub 2020 Aug 11.

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

Shintaro Akiyama  1 , Akihiro Yamada  2 , Dejan Micic  1 , Atsushi Sakuraba  3
Affiliations
Meta-Analysis

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

Shintaro Akiyama et al. J Am Acad Dermatol. 2021 Mar.

Abstract

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 (Mantel-Haenszel 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.

Keywords: IL12/23 and IL23 antagonists; autoimmune diseases; meta-analysis; noninfectious interstitial lung disease; respiratory tract infections.

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Figures

Fig 1
Fig 1
Flow chart of the assessment of the studies identified in the meta-analysis. IL, Interleukin; RCT, randomized controlled trial.
Fig 2
Fig 2
Meta-analysis of the Mantel-Haenszel (MH) risk difference of respiratory tract infections with IL-12/23 and IL-23 antagonists. CI, Confidence interval; IL, interleukin.
Fig 3
Fig 3
Meta-analysis of Mantel-Haenszel (MH) risk difference of infectious pneumonia with IL-12/23 and IL-23 antagonists. CI, Confidence interval; IL, interleukin.
Fig 4
Fig 4
Meta-analysis of the Mantel-Haenszel (MH) risk difference of noninfectious interstitial lung disease with IL-12/23 and IL-23 antagonists. CI, Confidence interval; IL, interleukin.
See this image and copyright information in PMC

Comment in

  • Commentary.
    Shin DB, Syed MN, Gelfand JM. Shin DB, et al. J Am Acad Dermatol. 2021 Mar;84(3):e161-e162. doi: 10.1016/j.jaad.2020.10.001. Epub 2020 Oct 8. J Am Acad Dermatol. 2021. PMID: 33039482 Free PMC article. No abstract available.

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