INTRODUCTION
Atopic dermatitis (AD) is an inflammatory skin disease marked by intense pruritus, impaired skin barrier function, and recurrent flares.1 Its prevalence in the United States is estimated to range from 8.7% to 18.1%, and an estimated 2.6% of individuals are affected by AD globally.2,3 Disease burden can manifest in various ways, including lower quality-of-life scores, reduced sleep quality, and increased workplace absenteeism.4,5
There are now many FDA-approved treatments for moderate-to-severe AD, including biologic medications like dupilumab, tralokinumab, nemolizumab, and lebrikizumab, and oral agents such as the JAK inhibitors upadacitinib and abrocitinib. While biologics and JAK inhibitors show robust efficacy as monotherapy in clinical trials, in real-world practice, cases of recalcitrant AD often remain inadequately controlled on monotherapy alone. To date, little is known about the use of dual therapy with lebrikizumab and JAK inhibitor therapy.
We present a small cohort of patients treated with dual therapy, lebrikizumab and either upadacitinib or abrocitinib for moderate-to-severe recalcitrant AD inadequately controlled on monotherapy alone. This study aims to provide real-world evidence on the efficacy and safety of lebrikizumab combined with JAK inhibitors, a regimen not yet formally evaluated in published literature.
MATERIALS AND METHODS
We performed a retrospective chart review of patients who received lebrikizumab and a JAK inhibitor therapy simultaneously for the treatment of atopic dermatitis at Mount Sinai Dermatology from September 2024 to September 2025. Variables extracted included demographic data, physical exam description, comorbidities, therapeutic regimen, dosing, and temporal data regarding treatment. Descriptive statistics were reported as n (%), mean ± SD, and median (IQR).
Body surface area (BSA) was used as the primary indicator of treatment response. When BSA was available, improvement was considered a decrease in BSA between the initiation of dual therapy and one-month follow up, four-month follow up, or both. If BSA data were not available, physician assessment from clinical notes was utilized to determine response.
RESULTS
There were 9 patients with an average age of 28.11 ± 10.55 years. The cohort was predominantly female (78%, n=7) and Caucasian (56%, n=5). The median duration of monotherapy was 413 days (IQR: 273-549 days), with a range from 178 to 1225 days (mean: 509.44 ± 360.5). The median duration of dual therapy was 232 days (IQR: 64-264 days), with a range of 30 to 325 days (mean: 180 days ± 107.27). Of the 9 patients on dual therapy, at the last follow up 44% (n=4) continued treatment and 33% discontinued (n=3), while two patients transitioned from upadacitinib and lebrikizumab to abrocitinib and lebrikizumab (Table 1).
Of the three patients who discontinued dual therapy, two were due to insurance coverage issues, and only one was due to insufficient response to the medication regimen. It is also important to note that of the two patients who discontinued treatment for alternative reasons (insurance), one saw improvement while on dual therapy.
Two patients were placed on an alternative combination of lebrikizumab and a JAK inhibitor. Both started with Upadacitinib/lebrikizumab. One was switched directly to abrocitinib/lebrikizumab, and the other started this regimen after a long period of lebrikizumab monotherapy (186 days). Notably, the patient who had a period of monotherapy between dual Lebrikizumab/JAK inhibitor combinations initially discontinued Upadacitinib/Lebrikizumab due to JAK-induced acne despite a positive clinical response (Subject 4). This patient went on to experience significant flaring on lebrikizumab alone, and therefore abrocitinib was added to lebrikizumab therapy with the goal of controlling the acute state.
Positive treatment response was seen in most of the cohort as a result of dual therapy (n=6/9, 67%). Of those who did not see a positive response (n=3), one had a worsening BSA, another saw a plateau in response, leading them to switch to a different combination of lebrikizumab/JAK inhibitor, and the third had an inadequate response to treatment.
Adverse events were limited and included known side effects of medications used, such as nausea or JAK inhibitor-induced acne. In only one instance did side effects contribute to the decision to discontinue dual regimen, otherwise the cohort had adequate tolerability of the treatment. No severe adverse events were seen.
