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 18 August 2022, a systematic review was performed to collect the premarketing and postmarketing 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 five RCTs and 23 case series; overall, 1719 patients were included, and the safety of 6 JAK-I was assessed (baricitinib, brepocitinib, deuruxolitinib, ritlecitinib, ruxolitinib and 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 postmarketing surveillance, which should be maintained on a long-term basis.