Immune-related adverse events (irAEs) in ankylosing spondylitis (AS) patients treated with interleukin (IL)-17 inhibitors: a systematic review and meta-analysis

Hossein Azadeh; Reza Alizadeh-Navaei; Alireza Rezaiemanesh; Misagh Rajabinejad

doi:10.1007/s10787-022-00933-z

Immune-related adverse events (irAEs) in ankylosing spondylitis (AS) patients treated with interleukin (IL)-17 inhibitors: a systematic review and meta-analysis

Inflammopharmacology. 2022 Apr;30(2):435-451. doi: 10.1007/s10787-022-00933-z. Epub 2022 Feb 21.

Authors

Hossein Azadeh¹, Reza Alizadeh-Navaei², Alireza Rezaiemanesh³, Misagh Rajabinejad^{4

5}

Affiliations

¹ Department of Internal Medicine, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
² Gastrointestinal Cancer Research Center, Non-Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran.
³ Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
⁴ Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. misagh.ra@gmail.com.
⁵ Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, 18 km khazarabad, Sari, Iran. misagh.ra@gmail.com.

PMID: 35188599
DOI: 10.1007/s10787-022-00933-z

Abstract

Background: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease characterized by immune system dysregulation and inflammation in the joints. Interleukin (IL)-17 inhibitors are new biological drugs used to treat AS. In this study, we aimed to assess the risk of immune system-related AEs due to targeting IL-17 or IL-17R.

Methods: The CENTRAL, PubMed, Scopus, Google Scholar, Clinical Trials Registry, and ICTRP were searched for randomized clinical trials (RCTs) and non-RCTs until February 2021. The risk of irAEs in patients treated with IL-17 inhibitors compared to the placebo or a drug-free control was evaluated. In studies that reported AEs of the IL-17 inhibitors at several different time points, we compared the number of cases/100 patient-year in which irAEs were reported. Subgroup analyses were also performed based on the dose and type of drugs.

Results: Thirteen studies of 1848 AS patients treated by IL-17 inhibitors (secukinumab, ixekizumab, bimekizumab, and netakimab) and 764 participants who received a placebo were included. The risk of some AEs related to immune function in patients under IL-17 inhibitors treatment was significantly higher than that of the placebo group, including infection and infestation (risk difference RD = 0.09, P = 0.02), nasopharyngitis (RD = 0.04, P < 0.001), opportunistic infections (RD = 0.01, P = 0.04), and neutropenia (RD = 0.04, P = 0.03). Besides, the results of the Cochran Q test showed that there were significant differences between the occurrence of some AEs over time, including infection and infestations (p < 0.001, RCTs), upper respiratory tract infections (p < 0.001, non-RCTs), urinary tract infections (p < 0.001, non-RCTs), and diarrhea (p < 0.01, RCTs).

Conclusions: The most common immune system-related AEs in patients treated with IL-17 inhibitors are mucosal and opportunistic infections.

Keywords: Ankylosing spondylitis (AS); Immune-related adverse events (irAEs); Interleukin (IL)-17 inhibitors; Randomized controlled trial (RCT).

Publication types

Meta-Analysis
Review
Systematic Review

MeSH terms

Antibodies, Monoclonal / therapeutic use
Antibodies, Monoclonal, Humanized
Humans
Interleukin Inhibitors
Spondylitis, Ankylosing* / drug therapy

Substances

Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Interleukin Inhibitors
netakimab