Long-Term Effectiveness and Discontinuation of Dupilumab in Patients With Atopic Dermatitis (2024)

• ¹National Expertise Center for Atopic Dermatitis, Department of Dermatology and Allergology, University Medical Center Utrecht, Utrecht, the Netherlands

• ²Department of Dermatology, University Medical Center Groningen, Groningen, the Netherlands

• ³Department of Dermatology, Reinier de Graaf Hospital, Delft, the Netherlands

• ⁴Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands

• ⁵Department of Dermatology, Spaarne Gasthuis, Hoofddorp, the Netherlands

• ⁶Department of Dermatology, University Medical Center Maastricht, Maastricht, the Netherlands

• ⁷Department of Dermatology, Meander Medical Center, Amersfoort, the Netherlands

• ⁸Department of Dermatology, St Antonius Hospital, Nieuwegein, the Netherlands

• ⁹Department of Dermatology, Haga Hospital, Den Haag, the Netherlands

• ¹⁰Department of Dermatology, Diakonessenhuis, Utrecht, the Netherlands

• ¹¹Department of Dermatology, Medical Center Leeuwarden, Leeuwarden, the Netherlands

• ¹²Department of Dermatology, Catharina Hospital, Eindhoven, the Netherlands

• ¹³Department of Dermatology, Isala Hospital, Zwolle, the Netherlands

• ¹⁴Department of Dermatology, IJsselland Hospital, Capelle aan den IJssel, the Netherlands

• ¹⁵Department of Dermatology, Radboud University Medical Center, Nijmegen, the Netherlands

Key Points

Question What is the clinical effectiveness of dupilumab for long-term use in patients with atopic dermatitis (AD), and what are reasons to discontinue dupilumab treatment?

Findings In this 5-year cohort study of 1286 patients with AD, dupilumab maintained its clinical effectiveness, while two-thirds of patients tapered dupilumab to a dosing interval of mostly every 3 or 4 weeks. 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 over time; however, 23.7% of patients discontinued treatment during this follow-up period, mainly due to adverse events and/or ineffectiveness.

Meaning Dupilumab may be an effective and safe therapeutic option for the long-term treatment of patients with AD.

Importance Limited data are available on the long-term effectiveness and safety of dupilumab for atopic dermatitis (AD) in daily practice.

Objective To evaluate clinical effectiveness and reasons for discontinuation of dupilumab treatment in children, adults, and older adults with AD with up to 5 years of treatment in daily practice.

Design, Setting, and Participants This prospective multicenter cohort study was conducted using the BioDay registry (4 academic and 10 nonacademic hospitals in the Netherlands) to identify patients with AD of all ages who were treated with dupilumab between October 2017 and December 2022.

Main Outcomes and Measures Clinical effectiveness was evaluated by the Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), and numeric rating scale (NRS) for pruritus, stratified by children (<18 years), adults (18-64 years), and older adults (≥65 years). In addition, time to response, treatment responders, EASI subscores, second treatment episodes, and thymus- and activation-related chemokine and eosinophil levels were assessed. For patients who discontinued dupilumab, the reason for discontinuation was evaluated.

Results In total, 1286 patients with AD (median [IQR] age, 38 [26-54] years; 726 [56.6%] male) were treated with dupilumab, including 130 children, 1025 adults, and 131 older adults. The median (IQR) follow-up time was 87.5 (32.0-157.0) weeks. Most patients maintained controlled AD, with EASI of 7 or lower and NRS for pruritus of 4 or lower varying between 78.6% and 92.3% and 72.2% and 88.2% for up to 5 years of treatment, respectively, while up to 70.5% of all patients prolonged the dosing interval to mostly 300 mg every 3 or 4 weeks. Mean EASI and NRS for pruritus were 2.7 (95% CI, 1.2-4.2) and 3.5 (95% CI, 2.7-4.3), respectively, after 5 years of treatment. Statistically significant differences between age groups were found over time for EASI and IGA; however, differences were rather small (week 52: EASI, 0.3-1.6; IGA, 0.12-0.26). No statistically significant differences between age groups were found for NRS for pruritus. Median thymus- and activation-related chemokine levels considerably decreased from 1751 pg/mL (95% CI, 1614-1900 pg/mL) to 390 pg/mL (95% CI, 368-413 pg/mL) after 6 months of treatment and remained low. Median eosinophil levels temporarily increased up to week 16, with a subsequently statistically significant decrease over time. In total, 306 patients (23.8%) discontinued dupilumab after a median (IQR) of 54.0 (29.0-110.00) weeks, with adverse events among 98 patients (7.6%) and ineffectiveness among 85 patients (6.6%) as the most frequently reported reasons. Forty-one patients (3.2%) restarted dupilumab, and most of these patients recaptured response.

Conclusions and Relevance In this cohort study with up to 5 years of follow-up, dupilumab maintained its clinical effectiveness, while two-thirds of patients tapered to a dosing interval of every 3 or 4 weeks. Treatment was discontinued in 23.8% of patients mainly due to adverse events and/or ineffectiveness.

Dermatology Atopic Dermatitis

Citation

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

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