Selective JAK1 inhibitors, upadacitinib and abrocitinib, seem to be effective well-tolerated therapies for moderate-to-severe AD, with good oral bioavailability as well as a lack of immunogenicity, addressing some of the limitations of biologics. If approved, they may be included in the therapeutic algorithms for AD and may provide an answer to the unmet needs of patients who do not respond or lose treatment response, do not tolerate or have contraindications to conventional systemic agents and dupilumab, or refuse an injectable treatment. How these agents will be positioned in the therapeutic ladder of AD is yet to be determined. Even though there are no published head-to-head studies, the efficacy of upadacitinib (69 and 80% with EASI75 over 16 weeks with the 30-mg dose in the phase IIb study and phase III study, respectively) and abrocitinib (at least 60% with EASI75 over 12 weeks with the 200-mg dose in both JADE MONO trials) seems to be superior to dupilumab (40–50% with EASI75 over 16 weeks in phase III clinical trials, SOLO 1 and 2) and the safety profile of JAK1 inhibitors may confer superiority over traditional oral agents, namely methotrexate and cyclosporine. Head-to-head clinical trials comparing selective JAK1 inhibitors with oral conventional agents, such as cyclosporine, and dupilumab (already ongoing), as well as the price will be helpful in the elaboration of treatment strategies.
Finally, increasing therapeutic options for treating AD will offer a better and more adequate management of this disease, considering individual factors such as disease and patients' characteristics and needs, which should drive treatment decision making. Based on the promising results so far and the large number of ongoing clinical trials, it is possible that JAK inhibitors, particularly selective JAK1 inhibitors, will become an important part of the treatment armamentarium for AD in the future.
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Am J Clin Dermatol. 2020;21(6):783-798. © 2020 Adis Springer International Publishing AG