BH19 ‘JAK in the box?’ Long-term safety concerns with oral Janus kinase inhibitors for alopecia areata

Abstract Janus kinase (JAK) inhibitors have emerged as a promising oral therapeutic option for alopecia areata (AA), an autoimmune condition characterized by hair loss. These therapies demonstrate clinical efficacy with hair regrowth even in long-standing cases of AA. However, their broad immunomodulatory effects raise concerns about long-term safety. JAK inhibitors disrupt multiple signalling pathways used by type I and type II cytokines, leading to significant reductions in T cells, natural killer cells and macrophage activation. Although short-term clinical trials support their efficacy and tolerability, the long-term safety profile in AA remains poorly understood, necessitating an evaluation of potential risks. A literature review of clinical trials evaluating the safety profile of JAK inhibitors in AA was conducted. Relevant studies were identified through a structured search of PubMed, using keywords such as ‘alopecia areata’, ‘side effects’ and ‘JAK inhibitors’. Inclusion criteria encompassed randomized controlled trials reporting treatment-emergent adverse events (AEs) and serious AEs. Exclusion criteria included nonhuman trials, case reports and lack of full-text availability. Using these selection criteria, 15 studies were identified. Data extraction focused on length of follow-up of AEs, treatment-emergent AEs and serious AEs. The findings were synthesized to provide an overview of the safety profiles of baricitinib, ritlecitinib, deuruxolitinib, ivarmacitinib and other JAK inhibitors. Long-term safety data were scarce, with only one study (the phase IIb/III ALLEGRO trial on ritlecitinib) extending to 2 years, while others had follow-ups of 52 weeks or shorter. The most common treatment-emergent AEs included upper-respiratory-tract infections, acne and headache. The incidence of serious AEs remained low across trials. In trials involving baricitinib and ritlecitinib, there were isolated reports of malignancies, particularly squamous cell carcinoma, melanoma and breast cancer. There was a single report of thromboembolic events and one case of myocardial infarction in a patient with pre-existing cardiovascular risk factors. JAK inhibitors were generally well tolerated, with most AEs being mild to moderate within a period of 2 years. Serious infections and malignancies were rare, and no increased risk of thromboembolism or cardiovascular events was observed beyond isolated cases. While the short-term safety profile (24–52 weeks) appears favourable, data on long-term effects remain limited beyond 2 years. Given the chronic nature of AA and the potential for extended use of JAK inhibitors, further long-term studies are necessary to better assess the risks of malignancies, cardiovascular events and other rare but serious AEs associated with this drug class. Although short-term studies indicate efficacy and tolerability, the absence of longitudinal research underpins the need for cautious clinical use and informed patient decision making.