Adverse events in patients treated with Jak-inhibitors for alopecia areata: a systematic review.

Recently, the impressive efficacy of JAK-inhibitors (JAK-I) in alopecia areata (AA) has been described in several studies; however, to date, there is limited information on the safety of JAK-I in AA patients. For this reason, on the August 18 th 2022, a systematic review was performed to collect the pre-marketing and post-marketing data on the safety of JAK-I in patients treated for AA, evaluating for each molecule the reported adverse events (AEs) in indexed literature and their frequency. The keywords "alopecia areata" AND "Jak-inhibitors OR Janus-kinase Inhibitors" were searched on PubMed, Embase, and Cochrane databases. Of 407 studies retrieved, 28 papers met the requirements and were used in our review, including 5 RCTs and 23 case series, overall 1719 patients were included and the safety of 6 JAK-I was assessed (baricitinib, brepocitinib, deuruxolitinib, ritlecitinib, ruxolitinib, tofacitinib). Systemic JAK-I were well tolerated, most of the AEs were mild, and the withdrawal rate for AEs was very low and inferior to placebo in controlled studies (1.6% vs. 2.2%). Laboratory abnormalities represented 40.1% of AEs associated with oral JAK-I, which mostly included the rise in cholesterol, transaminase, triglycerides, creatine phosphokinase (CPK), and sporadic cases of neutro/lymphocytopenia. The remaining AEs involved the respiratory tract (20.8%), the skin (17.2%), the urogenital (3.8%), or the gastroenterological (3.4%) tract. Increased rates of infections involved not only the upper (19.0%) and lower (0.3%) respiratory tract, but also the urogenital system (3.6%), and the skin (4.6%). Isolated cases of grade 3 to 4 AEs have been reported, including myocardial infarction, hypertensive urgencies, cellulitis, rhabdomyolysis, neutropenia, and high elevation of creatinine kinase. No fatal outcomes were reported. AEs reported with topical formulation included scalp irritation and folliculitis. The main limit of this review is the lack of data related to post-marketing surveillance, which should be maintained on a long-term basis.