Dupilumab Shows Greatest Rate of 2-Year Drug Survival Among Atopic Dermatitis Drugs

Dupilumab therapy shows the highest and most sustained 2-year drug survival among targeted atopic dermatitis drugs, new data suggest, though Janus Kinase (JAK) inhibitors show a lower level of persistence largely due to ineffectiveness and adverse events.1

These data resulted from a recent analysis of 2-year drug survival rates of JAK inhibitors as well as biologic therapies for patients living with atopic dermatitis. The study was written by investigators such as Lian F. van der Gang, a PhD candidate from University Medical Center Utrecht.

“This study aimed to compare the 2-year drug survival of biologics and JAKi and identify associated predictors, and secondarily to evaluate the impact of new targeted therapies on dupilumab drug survival,” van der Gang et al wrote.1

Design and Notable Findings

van der Gang and colleagues noted the importance of drug survival analysis as an indirect metric to indicate a treatment's effectiveness and tolerability. Additionally, they highlighted the metric's reflection on not only clinical outcomes but also decision-making among clinicians and patients. In addition to their aim of assessing JAKi and biologics in terms of drug survival, the investigators' secondary aim was to look at whether the introduction of additional targeted drugs impacted survival rates for dupilumab.

In this evaluated, adults aged 18 years or older with the skin disease were included who were also treated in routine clinical practice with abrocitinib, dupilumab, tralokinumab, upadacitinib, or baricitinib. The multi-center BioDay registry was used to find patients, and these individuals had initiated therapy in the period between January 2021 - October 2024. Drug survival was determined by van der Gang and coauthors via a Kaplan–Meier analyses.

It was stratified according to prior exposure to biologics or JAKi as well as by participants' rationale for drug discontinuation. Those who had remained on drug at the conclusion of follow-up, were lost to follow-up, or ended their treatments because of a desire to become pregnant or due to well-controlled disease were censored.

The investigative team used Cox proportional hazards models to assess any differences between medications and predictors of drug cessation. The team handled missing values via multiple imputation with 50 datasets. Necessary adjustments for multiple comparisons were conducted through the false discovery rate. For van der Gang et al's secondary analysis, all dupilumab treatment episodes between 2017 - 2024 were included, with the availability of alternative targeted drugs incorporated as a time-dependent variable.

Overall, the investigators assessed 227 tralokinumab, 865 dupilumab, 144 abrocitinib, 106 baricitinib, and 241 upadacitinib treatment episodes over the course of the study. Dupilumab was most often prescribed as the initial targeted medication, accounting for 82.1% of treatment episodes. Additionally, they found tralokinumab was implemented as first-line therapy in 44.9% of cases.

In contrast, van der Gang and colleagues found JAK inhibitors were predominantly initiated following prior targeted treatments, including abrocitinib in 125 treatment episodes (86.8%), baricitinib in 75 episodes (70.8%), and upadacitinib in 203 episodes (84.2%). Patients who were biologic- and JAKi-naïve saw drug survival rates at 1 and 2 years of 84.9% and 77.3% for dupilumab, 60.2% and 27.1% for abrocitinib, 72.5% and 47.6% for tralokinumab, 46.7% and 42.8% for baricitinib, and 72.6% and 63.5% for upadacitinib, respectively.

The investigative team found lower drug survival generally among subjects showing prior biologics or JAKi exposure. In this experienced cohort of patients, 1- and 2-year survival rates were 53.7% and 27.8% for abrocitinib, 82.9% and 68.1% for dupilumab, 29.6% and 22.4% for baricitinib, 61.3% and 49.4% for upadacitinib, and 59.8% and 49.6% for tralokinumab. Among both naïve and experienced individuals, the team concluded treatment discontinuation appeared most often due to insufficient drug effectiveness (20.6%), followed by adverse events 13.7%.

During treatment discontinuations resulting from issues with efficacy, van der Gang and coauthors found 95.7% of such patients had an Eczema Area and Severity Index (EASI) score exceeding 7 and/or a Numeric Rating Scale (NRS) score for pruritus over 4. The remaining individuals discontinued treatment mainly due to persistent involvement of the face or hands or due to the initiation of concomitant systemic drugs.

In the study's secondary analysis, the investigators observed a link between the availability of additional targeted drugs and a marked reduction in dupilumab persistence. Specifically, they identified a twofold higher risk of therapy discontinuation following entrance of new options into the market (HR 2.0, 95% CI 1.4–2.5; P < .0001).

“This study highlights that the absence of alternative targeted therapies results in significantly longer drug survival, indicating that treatment availability influences drug survival outcomes," they concluded.1 "Additionally, drug survival was generally lower in biologic-/JAKi-experienced patients."

References

1. LF van der Gang, CM Boesjes, NPA Zuithoff, et al. Drug Survival in Atopic Dermatitis: Comparison of Biologics and JAK Inhibitors in the BioDay Registry. Allergy (2025): 1–5, https://doi.org/10.1111/all.70187.

2. van den Reek JMPA, Kievit W, de Jong EMGJ, et al. Drug Survival Studies in Dermatology: Principles, Purposes, and Pitfalls. J Invest Dermatol. 2015 Jul;135(7):1-5. doi: 10.1038/jid.2015.171. PMID: 26066896.