George Varigos
Acne has been found to be a side effect published in the recent clinical trials of Jak Inhibitors treating patients with atopic eczema. The incidence of acne in the trials, for Upadacitinib 15 mg (30 [10%] of 300 patients) and upadacitinib 30 mg (41 [14%] of 297 patients) more than the placebo group (six [2%] of 304 patients).(1) Similarly with Abrocitinib a dose-related increase in acne (4.7%, 1.6%, and 0% for 200-mg, 100-mg, and placebo groups, respectively (2).
As we move to treat our atopic eczema patients with these new therapies, it is important we advise our patients but also understand the pathogenesis that may explain this clinical occurrence.
It may also be relevant that in rheumatological trials of the same JAK inhibitors the presentation of Acne was not as common as in the Atopic trials.
The finding recently of the skin Innate Lymphoid cells (ILCs) residing in the skin are heterogenous and having functions which play roles in homeostasis of the skin microbiome and also epidermal and appendage functions may be significant (2). ILCs play critical roles in host protective immunity such as the regulation of barrier and microbial homeostasis, metabolism, and tissue repair.
The paper will illustrate how JAK inhibitors affect the pathways of cytokines involved in the atopic pathology but also in doing so also have consequences on the ILC function and subsequent effects. In contrast the recent finding of activation of the JAK 1 pathway in acne, which emphasises a paradox (4). The ILCs may be an explanation for the appearance of acne in these JAK inhibitor clinical trials but not forgetting that there is redundancy or complexity in the system.
This presentation will attempt to highlight the important reasons and why acne is occurring in these atopic eczema JAK inhibitor trials.