No Increased Risk of Thromboembolic Events During 6‐Month Treatment With Baricitinib in Patients With Alopecia Areata

In January 2023, the European Medicines Agency (EMA) issued an alert on venous thromboembolism (VTE) risk linked to Janus kinase inhibitors (JAKi) in chronic inflammatory diseases, based on post-marketing data from rheumatoid arthritis (RA) patients treated with tofacitinib [1]. However, this may be biased, as RA is itself a known independent risk factor for VTE. Furthermore, JAKi vary in enzyme selectivity and thus in their effects [2]. The present study aimed: (1) to investigate VTE risk factors in a cohort of patients with alopecia areata (AA) eligible for baricitinib therapy and (2) to assess any change in laboratory VTE markers after 6 months of baricitinib treatment. A prospective observational study was conducted involving patients aged ≥ 18 years with moderate-to-severe AA, who were candidates for baricitinib 4 mg treatment, and who consecutively presented at our department between July 2023 and July 2024. Baseline demographic and clinical data were collected at the screening visit and reported in Table 1. In addition, a thorough medical history was obtained to identify patients with major (a previous VTE episode) or minor (smoking status, active malignancies, prior thrombophlebitis, family history of VTE, recent trauma or fractures, use of estrogen-progestin contraceptives, prolonged immobilization, major recent surgeries, and recurrent miscarriages) clinical risk factors for VTE. Furthermore, antiphospholipid antibodies (lupus anticoagulant, anti-cardiolipin, anti-β2 glycoprotein I), antithrombin III, protein C, protein S, homocysteine, and factor VIII levels were evaluated at baseline and after 6 months of treatment. Genetic risk factors for VTE, such as prothrombin G20210A and factor V Leiden mutation, were also evaluated at baseline. The characteristics of these factors and their role in VTE risk have been reported in Mendeley Table S1 (https://doi.org/10.17632/8288gnw6fh.1). Treatment with baricitinib would have been contraindicated in the presence of a major risk factor or two minor ones. Forty-seven patients with moderate-to-severe AA were assessed for eligibility for baricitinib treatment and were included in the study. None of the screened patients presented a contraindication to the treatment according to the previously reported criteria. In detail, regarding clinical VTE risk factors at baseline, 8/47 (17%) patients were active smokers, 5 women (10.6%) were using combined estrogen-progestin contraceptive pills, and one (2.1%) patient had a history of superficial thrombophlebitis. The major and minor laboratory risk factors for VTE at baseline are listed in Table 2. None of our patients presented major risk factors. During baricitinib treatment, no thrombotic events occurred, although two patients (4.2%) experienced bone fractures, which are known clinical risk factors for VTE. After 6 months of continuous therapy, laboratory examinations were performed in 37/47 patients, showing no changes in the majority of patients (Table 2 and Mendeley Table S2 (https://doi.org/10.17632/8288gnw6fh.1)) but a significant decrease in mean Factor VIII levels (119.1% to 101.8%, p = 0.019). Our study demonstrated that none of the enrolled AA patients showed either VTE or an increased risk of developing VTE, and this is in line with large-scale observational studies [3]. Moreover, no changes in laboratory VTE risk factors were detected during treatment with baricitinib, and instead, a significant reduction in Factor VIII was observed. This is an inflammatory marker and is considered one of the causative factors of the increased risk of VTE in RA patients [4]. Our finding is in line with the data from the baricitinib AA clinical trial programme, which reported that the incidence rate of VTE in the treatment groups was low (0.10 per 100 patient-years) [5]. The small sample size and the short follow-up period are the main limitations of our study. The main strength of this study is that it represents the first comprehensive evaluation of the predisposition of patients with AA undergoing baricitinib treatment to VTE events. In conclusion, our findings suggest that patients who are candidates for baricitinib treatment can be reassured about the risk of developing VTE adverse events. We emphasize that, in clinical practice, comprehensive thrombosis screening is not routinely required before starting JAKi therapy, except in patients with specific clinical risk factors, such as a personal or family history of thrombotic events or recurrent miscarriages. If laboratory tests identify risk factors for VTE, a consultation with a specialist can help determine whether prophylactic strategies are warranted or if an alternative treatment approach would be more suitable. Ethical committee approval was not required, as all diagnostic procedures performed were part of standard clinical practice and did not involve any interventions beyond routine patient care. The patients in this manuscript have given written informed consent to publication of their case details. G. Caldarola has received consulting fees, honoraria, and support for attending meetings from Abbvie, Lilly, Janssen, UCB, Novartis, and Leo Pharma; C. De Simone has received support for consulting fees, honoraria, and support for attending meetings from Abbvie, Lilly, Janssen, UCB, Leopharma, Sanofi, Almirall, Boehringer Ingelheim, and Bristol Myer Squibb; K. Peris has received support for consulting fees and honoraria from Abbvie, Almirall, Biogen, Celgene, Janssen, Galderma, Novartis, Lilly, Novartis, Pierre Fabre, Sandoz, Sanofi, and Sun Pharma outside of the submitted paper. All other authors declare that they have no conflicts of interest relevant to this manuscript. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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