The real-world, long-term risk of infections associated with dupilumab in atopic dermatitis: A global cohort study

Background: A low risk of infections was found in the randomized placebo-controlled trials of dupilumab in atopic dermatitis (AD). Dupilumab-associated real-life long-term risk of infections remains unclear. Objectives: To assess the risk of infectious complications in patients with AD managed by dupilumab relative to those treated with methotrexate and cyclosporine. Methods: Using the TriNetX global dataset, a retrospective cohort study comprised two distinct analyses comparing patients with AD under different treatments: (i) initiators of dupilumab (n = 10,913) versus methotrexate (n = 10,913) and (ii) initiators of dupilumab (n = 6943) versus cyclosporine (n = 6943). Study groups were compared regarding the risk of 32 infections during the initial 3 years following drug initiation. Propensity score matching was conducted to optimize inter-group comparability. Results: During the first year of treatment, relative to methotrexate and cyclosporine, dupilumab was associated with a decreased risk of herpetic (HR, 0.59; 95% CI, 0.47–0.74 and HR, 0.65; 95% CI, 0.50–0.85, respectively) and non-herpetic skin infection (HR, 0.55; 95% CI, 0.49–0.63 and HR, 0.68; 95% CI, 0.58–0.80, respectively) and systemic infections (HR, 0.39; 95% CI, 0.34–0.44 and HR, 0.47; 95% CI, 0.40–0.56, respectively). More specifically, relative to cyclosporine, dupilumab was associated with a reduced risk of pneumonia, urinary tract infection (UTI), upper respiratory tract infection (URTI), otitis media, sinusitis, herpes simplex, herpes zoster, hepatitis B virus (HBV) and HCV reactivation, cytomegalovirus, Epstein–Barr virus, infective gastroenteritis, influenza, parasitic diseases, pneumocystis jirovecii pneumonia, cellulitis, folliculitis, mucocutaneous candidiasis and dermatophytosis. Compared to methotrexate, dupilumab conferred a decreased risk of the aforementioned infections (apart from herpes simplex and HCV reactivation) as well as septicaemia, meningitis, encephalitis, osteomyelitis and tuberculosis. The risk of eczema herpeticum was not increased among dupilumab-treated patients. Conclusions: Dupilumab is associated with a reduced risk of a wide array of systemic and cutaneous infections. This agent might be preferred in patients with susceptibility to infections.