Drug Survival of Dupilumab Affected by Immunosuppressive Therapy, Older Age in AD

Investigator Global Assessment score of very severe atopic dermatitis (AD) was associated with dupilumab discontinuation due to adverse effects, although generally adequate 1-, 2-, and 3-year drug survival rates were also observed.

An increased risk for dupilumab discontinuation was shown in patients with atopic dermatitis (AD) who reported use of immunosuppressant drugs, were an older age, and had a very severe disease course. Results were published last week in JAMA Dermatology.

Approved for the treatment of patients with AD as young as 6 months, dupilumab, a fully human monoclonal antibody that blocks 2 key and central drivers of type 2 inflammation, interleukin (IL)-4 and IL-13, has been shown to significantly improve signs, symptoms, and quality of life burden associated with the disease.

The biologic, which is also approved for the treatment of asthma, chronic rhinosinusitis with nasal polyps, and eosinophilic esophagitis, has exhibited an adequate safety profile with long-term use, but the researchers of the present study note that results from clinical studies are difficult to generalize to daily practice as efficacy has been investigated under ideal and controlled circumstances in selected patients.

One key proxy measure to consider regarding the effectiveness, safety, adherence, and tolerability of dupilumab is drug survival, as frequent discontinuation rates and poor adherence of biologics may lead to inferior health outcomes.

“Predictor studies regarding dupilumab drug survival are limited and not specified for the reason of discontinuation. Consequently, little is known about which factors might be associated with the drug survival of dupilumab and whether certain clinical characteristics might be predictive for discontinuation owing to either ineffectiveness and/or adverse effects,” said the study authors.

They derived data from the multicenter prospective daily practice BioDay registry, comprising 4 university and 10 nonuniversity hospitals in the Netherlands, to investigate the drug survival of dupilumab in patients with AD aged 18 and older treated in daily practice and to identify its associated predictors.

Participants enrolled in the BioDay registry from October 2017 to December 2020 were included in the analysis. Drug survival rates at the 1-, 2-, and 3-year time points were analyzed by Kaplan-Meier survival curves, with associated characteristics evaluated using univariate and multivariate Cox regression analysis.

Many variables were assessed as potential predictors of dupilumab drug survival:

  • Sex, age, body mass index, and AD time of onset
  • Allergic asthma, allergic rhinitis, allergic conjunctivitis, and food allergy
  • Delta Eczema Area and Severity Index (EASI) score (the absolute difference between EASI score at week 4 and baseline), Investigator Global Assessment (IGA) score, and weekly average Numerical Rating Scale pruritus score
  • Use of immunosuppressive therapy at the start of dupilumab treatment
  • Eosinophil and thymus- and activation-regulated chemokine levels at the start of dupilumab treatment

A total of 715 adult patients with AD (mean [SD] age, 41.8 [16.0] years; 58.5% male) were included, in which 25.6% (n = 183) used immunosuppressive drugs at the start of treatment, 8.3% (n = 58) had an IGA score indicating very severe AD, and 6.7% (n = 48) showed no improvement or worsening of EASI score at week 4 (mean EASI score increase of 57.9%) compared with baseline and were defined as nonresponders at week 4.

“Responders at week 4 (n = 582) had a mean EASI score decrease of 55.3%,” said researchers.

Overall, the 1-, 2-, and 3- drug survival of dupilumab was 90.3%, 85.9%, and 78.6%, respectively, and was mostly associated with adverse effects (AEs). Drug survival rates with AEs as an event were 96.3%, 93.2%, and 92.6% after 1, 2, and 3 years, respectively, and corresponding ineffectiveness as an event was 96.5%, 95.7%, and 95.7%—indicating that after 2 years of dupilumab treatment, no additional patients discontinued dupilumab treatment owing to ineffectiveness.

Results from the multivariate model indicated that the characteristics associated with shorter drug survival owing to ineffectiveness were the use of immunosuppressant drugs at baseline (HR, 2.64; 95% CI, 1.10-6.37) and being a nonresponder at 4 weeks (HR, 8.68; 95% CI, 2.97-25.35).

Moreover, characteristics associated with shorter drug survival owing to AEs were the use of immunosuppressant drugs at baseline (HR, 2.69; 95% CI, 1.32-5.48), age 65 or older (HR, 2.94; 95% CI, 1.10-7.87), and an IGA score of very severe AD (HR, 3.51; 95% CI, 1.20-10.28).

“These data provide more insight and new perspectives regarding dupilumab treatment in AD and can contribute to the optimization of patient outcomes,” concluded the researchers. “In the coming years, daily practice registry data will provide longer follow-up data of new advanced systemic treatments, which will give information on dupilumab drug survival compared with these new systemic treatments.”

Reference

Spekhorst LS, de Graaf M, Zuithoff NPA, et al. Dupilumab drug survival and associated predictors in patients with moderate to severe atopic dermatitis: Long-term results from the daily practice BioDay registry. JAMA Dermatol. Published online August 10, 2022. doi:10.1001/jamadermatol.2022.3014