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.

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

Introduction: Atopic dermatitis (AD) patients have an increased risk of herpes zoster (HZ). The relationship of dupilumab, tralokinumab, upadacitinib, and abrocitinib to HZ incidence in AD patients remains unclear. Aim: To evaluate and compare the incidence and risk of HZ among patients with moderate to severe atopic dermatitis treated with advanced systemic therapies. Material and methods: Systematic searches were conducted in Ovid Medline and Embase. The primary outcome was incidence of HZ in patients with moderate to severe AD receiving placebo or the aforementioned treatments. A frequentist random-effects NMA was conducted with odds ratio. Results: Our search identified 16 trials comprising 10,689 patients. Upadacitinib was associated with a dose-dependent increase in the incidence of HZ compared to placebo (OR = 2.55 [1.09, 5.95] and (OR = 4.29 [1.89, 9.74], respectively) and compared to various dupilumab doses (OR = 4.48 [1.29, 15.57], 3.61 [1.28, 10.18] and 7.54 [2.21, 25.68], 6.09 [2.24, 16.52], respectively). Upadacitinib 30 mg was associated with a higher incidence of HZ when compared to upadacitinib 15 mg (OR = 1.68 [1.19, 2.38]). Abrocitinib 200 mg was associated with a higher increase in HZ compared to placebo (OR = 3.34 [1.34, 8.31]). According to SUCRA ranks, both JAK-1 inhibitors had a higher cumulative incidence of HZ compared to dupilumab. Conclusions: JAK-1 inhibitors are associated with a significantly higher incidence of HZ compared to dupilumab and placebo. Our results suggest that recombinant HZ vaccination should be highly considered for all adult patients prior to starting oral JAK-1 inhibitors.