Efficacy and safety of dupilumab in patients with severe chronic hand eczema with inadequate response or intolerance to alitretinoin: a randomized, double-blind, placebo-controlled phase IIb proof-of-concept study.

BACKGROUND: Effective treatment options for patients with chronic hand eczema (CHE) are scarce. Dupilumab is licensed for the treatment of moderate-to-severe atopic dermatitis and has shown promising results on hand eczema in other studies.

OBJECTIVE: To evaluate the efficacy and safety of dupilumab in adult patients with severe CHE (subtypes recurrent vesicular HE or chronic fissured HE) with an inadequate response/intolerance to alitretinoin, or when alitretinoin is medically inadvisable.

METHODS: In this 16-weeks, randomized, double-blind, placebo-controlled, proof-of-concept phase IIb trial, patients with severe CHE were randomized 2:1 to dupilumab 300mg or placebo subcutaneously every two weeks. Patients visited the outpatient clinic at initiation of the study drug, and every 4 weeks until 16 weeks of treatment. The primary end point was the proportion of patients achieving at least 75% improvement on the Hand Eczema Severity Index score (HECSI-75) at week 16. Adverse events were monitored during each visit. The study was registered on ClinicalTrials.gov (identifier NCT04512339).

RESULTS: In total, 30 patients were randomized, and 29 patients received the assigned study drug (dupilumab N = 20, placebo N = 9). At week 16, more patients achieved HECSI-75 in the dupilumab group than in the placebo group (95.0% [95% confidence interval (CI), 73.1%; 99.7.0%] versus 33.3% [95% CI, 9.0%; 69.1%]). Dupilumab also showed greater least square mean percentage change from baseline to week 16 in peak pruritus numerical rating scale than placebo (-66.5 ±10.7 [95% CI, -88.6; -44.5] versus -25.3 ±17.0 [95% CI, -60.1; 9.4]). Adverse events were similar between dupilumab and placebo groups and were mostly mild. There were no serious adverse events, nor did any of the adverse events lead to discontinuation of the study drug.

CONCLUSION: Dupilumab was efficacious and well tolerated. Larger studies of longer duration, are needed to provide more evidence on the efficacy of dupilumab in CHE. Moreover, larger studies could also enable comparisons between clinical subtypes or etiological diagnoses.