Effectiveness and Safety of Janus Kinase Inhibitors in Adults Aged ≥ 50 Years With Moderate‐To‐Severe Atopic Dermatitis and Substantial Cardiovascular Comorbidity: A Multicenter Real‐World Study

The treatment for moderate-to-severe atopic dermatitis (AD) has expanded with the introduction of biologics and Janus kinase inhibitors (JAKis). Although both drug classes are equally recommended in the EuroGuiDerm guidelines, emerging evidence, including network meta-analyses, suggests that JAKis may provide faster clinical responses than biologics [1]. However, following warnings issued by the European Medicines Agency (EMA), their use is often restricted to patients under 65 years without cardiovascular (CV) or thromboembolic risk factors. This has contributed to an age-related treatment bias that may lead to undertreatment in older adults, a population increasingly affected by AD yet consistently underrepresented in pivotal clinical trials [2]. Real-world data in this demographic are urgently needed. We conducted a multicenter, real-life, retrospective observational study across 15 dermatology referral centers, including adults aged 50 years or older with moderate-to-severe AD receiving continuous JAKi therapy for at least 16 weeks. Substantial cardiovascular comorbidity was defined as the presence of at least one cardiovascular risk factor (dyslipidaemia, hypertension, type 2 diabetes mellitus, or active smoking) or established cardiovascular disease. At least one post-baseline assessment was conducted between September 2021 and January 2025, with follow-up across 52 weeks. Per-protocol analyses were conducted, including a predefined subgroup analysis in patients ≥ 65 years, without imputation of missing data. Assessments were collected within predefined clinical windows; Week 16 was defined between Weeks 12 and 16. Safety and effectiveness were assessed at 4, 16, 24, and 52 weeks using overall Eczema Area and Severity Index (EASI) scores, the proportions achieving EASI 75/90/100, and minimal disease activity (MDA; EASI ≤ 3 and pruritus numerical rating scale [NRS-pruritus] ≤ 1). Patient-reported outcomes (NRS-pruritus and Dermatology Life Quality Index [DLQI]) were also collected. A total of 113 patients were included (Table 1). Median age was 60 years, and most had relevant comorbidities: 70% were overweight/obese, 66% had at least one cardiovascular (CV) risk factor (dyslipidemia 44%, hypertension 33%, type 2 diabetes 18%), and 34% were active smokers. Upadacitinib was the most frequently prescribed JAKi (n = 89; 54% at 30 mg/day), followed by abrocitinib (n = 13; 77% at 200 mg/day) and baricitinib (n = 11; all at 4 mg/day). Mean EASI decreased from 20.73 ± 9.28 at baseline to 2.24 ± 2 at Week 16 and remained stable through Week 52 (n = 40, 113, 97, and 80 at Weeks 4, 16, 24, and 52, respectively). At Week 16, 71% achieved EASI 90, 43% EASI 100, and 58% MDA, increasing to 84%, 62%, and 66% by Week 52. Descriptive analyses did not reveal major differences across JAKi subgroups or between patients aged ≥ 65 years (n = 27), although a non-significant trend toward poorer response was observed after prior JAKi exposure (Figure 1). DLQI and NRS-pruritus improved in parallel. Overall, 13% of patients (n = 15) experienced adverse events (Supplementary Table 1 available via Mendeley, https://doi.org/10.17632/sjcbn4kpft): 10 receiving upadacitinib, 3 abrocitinib, and 2 baricitinib. Event rates were comparable between patients aged < 65 and ≥ 65 years (13% vs. 14%), including infectious adverse events (2% vs. 3%, respectively). Most events were mild and none required hospitalization. Dose reduction allowed treatment continuation in 80% of cases. Discontinuation occurred in 7% (n = 8): five with upadacitinib (three due to adverse events—headache, acne, worsening of pre-existing cerebellar ataxia—and two due to insufficient response) and three with abrocitinib (lack of efficacy). Our findings are consistent with limited real-world evidence from Italian and Spanish cohorts of adults aged 50–60 years, where effectiveness and safety outcomes were comparable [3-5]. Importantly, no major adverse cardiovascular events, venous thromboembolism, malignancies, or serious adverse events requiring hospitalization were observed during follow-up. Our study includes patients with a high CV risk burden, which closely reflects routine clinical practice. Most published series—including ours—predominantly report upadacitinib, likely reflecting its extensive safety data across multiple indications, including giant-cell arteritis in elderly, high-cardiovascular-risk populations [6]. Although descriptive analyses did not suggest major differences in effectiveness across individual JAK inhibitors, these comparisons should be interpreted cautiously given the small and unbalanced subgroup sizes. Prior biologic exposure did not affect subsequent response, whereas previous JAKi use showed a non-significant trend toward reduced effectiveness. Collectively, these findings contribute to addressing the evidence gap in older adults, suggesting that age alone should not preclude JAKi use when appropriate clinical monitoring is ensured. Limitations include the retrospective design, modest sample size in the ≥ 65-year subgroup, and underrepresentation of abrocitinib and baricitinib. Nevertheless, our data add real-world evidence supporting the role of JAKi as an effective and well-tolerated therapeutic option in older adults with AD and cardiovascular risk factors. Prospective studies with larger, age-balanced cohorts are warranted to better define long-term safety and durability of response in this population. The authors have nothing to report. The study was approved by the institutional ethics committee (2025/106-DER-HUSC) of Hospital Universitari Sagrat Cor. All the publication of recognizable patient photographs or other identifiable material was obtained by the authors and included at the time of article submission to the journal stating that all patients gave consent with the understanding that this information may be publicly available. José Manuel Fernández Armenteros has received honoraria from AbbVie for lectures unrelated to the content of this manuscript. Joan Ceravalls has received honoraria from AbbVie for educational activities unrelated to the topic of this article. Francesca Corella Vicente has received honoraria for lectures or educational activities from AbbVie, Sanofi, and Leo Pharma, and support for attending meetings or travel from Pfizer, Almirall, and Novartis. Gemma Melé-Ninot has received honoraria for lectures or educational activities and has participated in advisory boards for Sanofi, AbbVie, Leo Pharma, Lilly, Almirall, and Novartis. Marta Bertolín-Colilla has received honoraria for lectures or educational activities from Sanofi, Almirall, AbbVie, and Pfizer, support for attending meetings or travel from Sanofi, Almirall, and Pfizer, and has participated in advisory boards for Almirall and Pfizer. Vicente Expósito-Serrano has received consulting fees, honoraria for lectures or educational activities, support for attending meetings or travel, and has participated in advisory boards. Ignasi Figueras-Nart has received honoraria for lectures or educational activities from AbbVie, La Roche-Posay, Lilly, Pierre Fabre, Regeneron, Vifor Pharma, Amgen, AstraZeneca, DKSH, Celgene, Leo Pharma, Novartis, Sanofi, Sobi, Pfizer, MSD, and Zuellig Pharma, and has participated in advisory boards for AbbVie, Lilly, Regeneron, Vifor Pharma, Amgen, AstraZeneca, Leo Pharma, Novartis, Sanofi, Pfizer, and Zuellig Pharma. Jorge Spertino has received honoraria for lectures or educational activities and has participated in advisory boards for AbbVie, Lilly, Leo Pharma, Novartis, Sanofi Genzyme, and Noucor. Montserrat Bonfill-Ortí has received honoraria for lectures or educational activities from Leo Pharma, AbbVie, Lilly, Novartis, Sanofi Genzyme, Roche, and Sun Pharma. Francisco Javier Melgosa Ramos has received consulting fees and honoraria for lectures or educational activities from Almirall, Amgen, Janssen, Leo Pharma, AbbVie, Lilly, Novartis, Sanofi Genzyme, Pfizer, and UCB. Mònica Munera Campos has received honoraria for lectures or educational activities from Lilly, Sanofi, Almirall, and Leo Pharma, and has acted as investigator for Lilly, Sanofi, Almirall, AbbVie, Pfizer, Leo Pharma, and Galderma. Víctor González Delgado has received honoraria for lectures or educational activities and support for attending meetings or travel from AbbVie, Sanofi Genzyme, and UCB. Drs Juan Jose Lluch-Galcerá, Ricardo Ruiz-Villaverde, Álvaro Prados Carmona, Sonia de la Fuente, Enrique Gómez de la Fuente, Nerea Mohino Farré, and Lydia Corbalán Escortell declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.