Janus kinase inhibitors for the treatment of atopic dermatitis: Real‐life data on efficacy and safety in light of the Pharmacovigilance Risk Assessment Committee recommended measures

Baricitinib (BARI), upadacitinib (UPA) and abrocitinib (ABRO) are Janus kinase inhibitors (JAKi) used in France to treat moderate-to-severe atopic dermatitis (AD) after failure of or contraindication to cyclosporine. In clinical trials, JAKi demonstrated good efficacy; the most frequent side effects were infections, acne and gastrointestinal disorders. In January 2023, the European Medicines Agency endorsed measures recommended by the Pharmacovigilance Risk Assessment Committee (PRAC) to minimize the risk of serious side effects, including cardiovascular conditions, venous thromboembolism (VTE), cancer, and serious infections, in patients receiving JAKi for several chronic inflammatory disorders. These recommendations followed a review of the results of a clinical trial including patients with rheumatoid arthritis (RA) receiving tofacitinib,1 an observational study of patients with RA receiving BARI,2 and advice from an expert group of physicians and patient representatives. Available data for the treatment of AD with JAKi are largely from clinical trials.3-6 This may lead to potential biases related to the inclusion criteria of these trials and the risk of under-representation of at-risk patients or patients with comorbidities.7 Very few real-life studies have been published to date, most including only few patients and/or with short-term results.8-10 To assess the effectiveness and safety of JAKi in real life, we conducted a multicentre cohort study that included all patients with AD receiving JAKi in routine practice with data from at least two visits. At visit 1, corresponding to JAKi initiation, patient and AD characteristics were recorded. At visit 2, corresponding to the last medical visit, AD severity, last JAKi intake, and the occurrence of any potential adverse events, with specific attention to cardiovascular diseases, VTE, cancer, infections and acne, were also collected. In all, 18 French centres that were members of Reso-Dermatologie included 214 patients (Table 1). Some patients received more than one JAKi; 136 received BARI (131 BAR 4 mg/day; five BARI 2 mg/day), 94 received UPA (62 UPA 30 mg/day, 32 UPA 15 mg/day) and 16 received ABRO (15 ABRO 200 mg/day, one ABRO 100 mg/day). At visit 1, most patients had severe AD (mean Eczema Area and Severity Index [EASI]: 23) and had previously received several systemic drugs, including biologics (dupilumab and/or tralokinumab). When considering the PRAC recommendations, 64% of patients were considered at risk, and half of the female patients were using an oral estroprogestative contraceptive. At the second visit, 79.4% of patients were still receiving a JAKi. The mean EASI was 4.8 ± 5.6 (range 0–34). In patients previously receiving biologics, 69% achieved a 75% improvement in EASI score. After a mean exposure of 10.8 ± 8.8 months (range 0.3–43.7), no cardiovascular event, VTE or cancer was reported. Four patients reported serious infections, 10 reported a herpes simplex virus infection, six reported a varicella-zoster virus infection and 24 reported acne. Pharmacovigilance Risk Assessment Committee recommendations were essentially based on RA data, but AD patients are generally younger and not overweight. Unlike RA, AD is not associated with an increased risk of thrombosis or solid cancer. Systemic treatments for AD, such as cyclosporine, oral corticosteroids and methotrexate, are not themselves free of serious side effects. Safety data and information obtained during our study support the positive benefit–risk profile of JAKi demonstrated in the pivotal trials, even in a population of patients with cardiovascular comorbidities and risk factors. Atopic dermatitis can severely affect patients' lives. As dermatologists, we have a duty to ensure the safety of our patients, but we must not deprive them of therapies that could improve their quality of life considerably. More than ever, real-life data and registries will be useful to reassure patients and the entire dermatology community about the safety of our treatments. The authors thank Dalila Simonian (project manager/director OMCCI) for her contribution to this project. Sheridan Henness, PhD, provided medical writing assistance with the preparation of this manuscript, funded by ResoMed. This manuscript was funded by ResoMed. Reguiai Ziad has received consulting fees and honoraria from Abbvie, Allmiral, Amgen, Bristol Myers Squibb, Celltrion, Eli Lily, Janssen-Cilag, Leo Pharma, Medac, Novartis, Pfizer, Sanofi, UCB; received personal fees for attending meetings and/or travel from Abbvie, Almirall, Eli Lily, Janssen-Cilag, Leo Pharma, Novartis, UCB, Sanofi; and received fees as an investigator from Abbvie, Almirall, Amgen, Boehringer-Ingelheim, Celltrion, Incyte, Janssen-Cilag, Leo Pharma, Novartis, Pfizer and UCB. Pierre André Becherel has received Consultant and/or members of boards and/or speaker fees from: Abbvie, Almirall, Amgen, Boehringer Ingelheim, BMS, Celgene, Eli-Lilly, Janssen, LEO Pharma, MSD, Pfizer, Sanofi and UCB. Anne-Claire Fougerousse has received speaker, consultant or investigator fees from Almirall, Abbvie, Boehringer Ingelheim, Janssen, Leo Pharma, Lilly, Novartis, Pfizer, Sanofi and UCB Pharma. Guillaume Chaby has nothing to declare. Jean Luc Perrot has received consultant fees from Sanofi, Lilly, Leo Pharma and Pfizer. Edouard Begon has received consultant fees from Lilly, Abbvie, UCB, Novartis, Sanofi and Janssen. Caroline Jacobzone-Lévêque has received consulting fees from Abbvie, Lilly, Amgen, Novartis, Sanofi and Léo Pharma. Claire Boulard has received speaker fees from Abbvie, Janssen, Leo Pharma, Novartis, Sanofi, UCB, Lilly and Almirall. Antoine Badaoui has received consulting fees from Novartis, Sanofi and Abbvie. Claire Poreaux has nothing to declare. Laurene David has nothing to declare. Nathalie Quiles-Tsimaratos has received consulting fees from Abbvie, Amgen, BMS, Janssen Cilag, Léo Pharma, Lilly, Novartis, Pfizer and UCB. Dominique Lons-Danic has received consulting fees from Abbvie, Almirall, Janssen, Leo Pharma, Lilly, Sanofi and UCB. Charlotte Fite has received Advisory Board fees from Abbvie, Sanofi, Janssen, UCB, Novartis, Almirall and Lilly. Anne-Laure Liegeon has received Advisory Board fees from Novartis, Janssen, UCB and Abbvie. Alexandra Patchinsky has nothing to declare. Josiane Parier has received consulting fees from Leo Pharma, Amgen, UCB, Almirall, Janssen, AbbVie, Novartis, Medac, Lilly and Sanofi. Charline Garcia has nothing to declare. Eric Estève has received consulting fees from Janssen, UCB, Abbvie, Lilly, Leo Pharma and Sanofi. Rima Mohty has nothing to declare. Laure Mery-Bossard has received consulting fees and honoraria from Abbvie, Sanofi, Novartis, Janssen, Lilly, Leo Pharma, Amgen, Almirall and UCB. François Maccari has received consulting fees from Almirall, Abbvie, Leo Pharma, Lilly, Pfizer and Sanofi. Patients have given oral informed consent to publication of their case details, in line with revised French Research Standard MR003. The data that support the findings of this study are available from the corresponding author upon reasonable request.