Dupilumab Maintains Effectiveness in AD for Up to 5 Years, But 1 in 4 Still Discontinue Treatment

Celeste Boesjes, MD
Credit: LinkedIn

Data from a new study shed light on the long-term effectiveness and reason for discontinuation among patients with atopic dermatitis using dupilumab (Dupixent).

Results of the study, which pooled data from more than 1200 patients at 14 hospitals in the Netherlands, suggest 70% used dupilumab for up to 5 years, with 2 in 3 able to taper their dosing interval to every 3 or 4 weeks. However, results also demonstrated 23.8% of patients discontinued use of dupilumab, pointing to adverse events or ineffectiveness as the reasoning.¹

“This study highlights the importance of multicenter registries to evaluate long-term treatment effects in large daily practice cohorts,” wrote investigators. “Future studies in patients who discontinued dupilumab due to controlled disease may contribute to the knowledge on the disease course and possible disease modification after treatment discontinuation.”

With its first approval in atopic dermatitis coming back in 2017, and subsequent expanded indications to include younger populations in 2019 and 2022, dupilumab has carved a role for itself as a standard of care for the dermatologic condition. However, most of these approvals have been based on trials less than 2 years in duration and, as investigators explained in the current study, much less data exists on long-term use of dupilumab.^1,2,3,4

With this in mind, a team led by Celeste Boesjes, MD, of the National Expertise Center for Atopic Dermatitis at the University Medical Center Utrecht, and colleagues designed the current study as an analysis of data from the ongoing, prospective, multicenter study called the BioDay registry. A registry pooling data from 4 academic and 10 nonacademic hospitals, the study consecutively enrolled adults and children with atopic dermatitis treated with dupilumab between October 2017 and December 2022.¹

A total of 1286 patients were identified for inclusion. This cohort included 130 children, 1025 adults, and 131 older adults. The overall cohort had a median age of 38 (Interquartile Range [IQR], 26 to 54) years, 56.5% were males, and the median follow-up time was 87.5 (IQR, 32 to 157) weeks.¹

The primary effectiveness outcomes of interest in the study were e Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), and the weekly average numeric rating scale (NRS) for pruritus in the past week, with plans for subgroup analyses stratified by patient age. Investigators also noted plans to assess rate of treatment discontinuation as well as reasoning for discontinuation.¹

Upon analysis, results indicated most patients maintained controlled atopic dermatitis, with rates of achievement for an EASI of 7 or less and NRS for pruritic of 4 or less ranging from 78.6% to 92.3% and 72.2% to 88.2% for up to 5 years of treatment, respectively. Investigators highlighted up to 80.5% of patients prolonged the dosing interval to mostly 300 mg every 3 or 4 weeks with dupilumab. The 5-year analysis pointed to mean EASI of 2.7 (95% CI, 1.2 to 4.2) and NRS for pruritus of 3.5 (95% CI, 2.7 to 4.3). Investigators pointed out no statistically significant differences between age groups were found for NRS for pruritus.¹

Additionally, results suggested the median thymus- and activation-related chemokine levels declined from 1751 pg/mL (95% CI, 1614 to 1900 pg/mL) to 390pg/mL (95%CI, 368 to 413 pg/mL) after 6 months of treatment, with these levels maintained for the duration of the study period. Further analysis found median eosinophil levels temporarily increased up to week 16, with a subsequent statistically significant decrease over time.¹

Assessment of discontinuation revealed 23.8% of patients discontinued use of dupilumab after a median of 54 (IQR, 29 to 110) weeks. The most common reasons for discontinuation of treatment were an adverse event or ineffectiveness, which were reported by 38% and 27.7% of those who discontinued treatment, respectively.¹

Investigators called attention to several limitations within their study to consider. These included missing data on the included outcomes due to the daily practice setting and the COVID-19 pandemic, a relatively low number of pediatric patients, and lack of a full 5-year follow-up of all patients.¹

“In this 5-year cohort study of 1286 patients with [atopic dermatitis], dupilumab maintained its clinical effectiveness, while two-thirds of patients tapered dupilumab to a dosing interval of mostly every 3 or 4 weeks,” added investigators.¹ “A fairly similar response was found among children, adults, and older adults, with statistically significant decreases in thymus- and activation-regulated chemokine and eosinophil levels that remained low overtime; however, 23.7% of patients discontinued treatment during this follow-up period, mainly due to adverse events and/or ineffectiveness.”

References:

1. Boesjes CM, Kamphuis E, de Graaf M, et al. Long-Term Effectiveness and Reasons for Discontinuation of Dupilumab in Patients With Atopic Dermatitis. JAMA Dermatol. Published online August 07, 2024. doi:10.1001/jamadermatol.2024.2517
2. Office of the Commissioner. FDA approves New Eczema Drug Dupixent. U.S. Food and Drug Administration. March 28, 2017. Accessed August 8, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-eczema-drug-dupixent.
3. Sanofi. FDA approves Dupixent® (dupilumab) for moderate-to-severe atopic dermatitis in adolescents. Sanofi US News. March 11, 2019. Accessed August 8, 2024. https://www.news.sanofi.us/2019-03-11-FDA-approves-Dupixent-R-dupilumab-for-moderate-to-severe-atopic-dermatitis-in-adolescents.
4. Sanofi. FDA approves Dupixent® (dupilumab) as first biologic medicine for children aged 6 months to 5 years with moderate-to-severe atopic dermatitis. Sanofi US News. June 7, 2022. Accessed August 8, 2024. https://www.sanofi.com/en/media-room/press-releases/2022/2022-06-07-20-45-00-2458243.