Systematic review and network meta-analysis of the risk of malignancy with biologic therapies and selective Janus kinase-1 inhibitors in atopic dermatitis.

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease with multifactorial pathophysiology. Biologic therapies, including dupilumab (IL-4/IL-13 inhibitor) and tralokinumab (IL-13 inhibitor), as well as selective Janus kinase-1 (JAK-1) inhibitors such as upadacitinib and abrocitinib, have been approved for the treatment of moderate to severe AD. However, their association with the incidence of malignancy in AD patients remains uncertain.

Aim: We conducted a systematic review and network meta-analysis (NMA) to investigate and compare the indidence and risk of malignancy in individuals with moderate-to-severe AD treated with abrocitinib, upadacitinib, tralokinumab, or dupilumab.

Material and methods: Systematic searches were conducted in Ovid MEDLINE and EMBASE that included AD, malignancy, biologic and advanced therapies. The primary outcome was incidence of malignancy in AD patients receiving placebo or at least one of the following advanced therapies: dupilumab, tralokinumab, abrocitinib or upadacitinib. A random-effects NMA was conducted with odds ratios and a frequentist model.

Results: Our search identified 11 trials comprising 10097 patients. The NMA did not show any statistically significant association between dupilumab or selective JAK-1 inhibitors and the incidence of malignancy up to an average of 41 weeks of treatment.

Conclusions: Our analysis revealed no statistically significant increased risk of malignancy and no significant difference in the incidence of malignancy between selective JAK-1 inhibitors and dupilumab for the treatment of AD up to an average follow-up of 41 weeks. Nevertheless, further prospective studies with longer follow-up periods are warranted to confirm the safety of these therapies and their impact on the risk of malignancy.