Researchers investigated the interleukin (IL)-4/IL-13 receptor blocker, dupilumab, which has been linked to autoimmune and inflammatory disorders sporadically. According to the study, the dual blockade of IL-4 and IL-13 via dupilumab was associated with immune responses skewed toward IL-23/IL-17 cytokine pathway-related diseases. The results were published in the Journal of Investigative Dermatology.

The authors determined that dupilumab was not associated with classic polygenic humoral-mediated autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and scleroderma (odds ratio [OR], 0.60; 95% credible interval [CrI], 0.38-0.96).

Their analysis comprised 37,848 adverse dupilumab reactions reported in the World Health Organization’s VigiBase database. The majority of adverse reactions occurred in the skin, eye, and musculoskeletal systems. The authors found that dupilumab was highly associated with seronegative arthritis (OR = 9.61), psoriasis (OR = 1.48), enthesitis/enthesopathy (OR = 12.65), and iridocyclitis (OR = 3.77). Notably, ankylosing spondylitis and inflammatory bowel disease were not definitively associated with dupilumab treatment.

The researchers then identified potential pathways relevant to adverse dupilumab reactions, including the fibroblast growth factor receptor (FGFR) and the FGFR2 pathway in particular. The microRNAs hsa-miR-21-5p and hsa-miR-335-5p were also reported as potential contributors to adverse drug reactions.

Dupilumab was associated with T helper 17-mediated disorders. The authors proposed that IL-4 and IL-13 are significant in tissue homeostasis and repair, and they further theorized that the disruption of these pathways may be relevant for other degenerative diseases, especially given the aortic aneurysms and keratoconus reactions reported in the database.

Reference: Bridgewood C, Wittmann M, Macleod T, et al. T Helper 2 IL-4/IL-13 Dual Blockade with Dupilumab Is Linked to Some Emergent T Helper 17‒Type Diseases, Including Seronegative Arthritis and Enthesitis/Enthesopathy, but Not to Humoral Autoimmune Diseases [published online ahead of print, 2022 Apr 6]. J Invest Dermatol. 2022;S0022-202X(22)00256-1. doi:10.1016/j.jid.2022.03.013