Introduction <p>A matching-adjusted indirect comparison (MAIC) was performed comparing the efficacy of delgocitinib and dupilumab in patients with atopic hand eczema (AHE), one aetiological subtype of chronic hand eczema (CHE).</p> Methods <p>DELTA 1/2 were phase 3 trials in which adults with moderate to severe CHE received delgocitinib cream 20&#xa0;mg/g or cream vehicle twice daily for 16&#xa0;weeks. LIBERTY-AD-HAFT was a phase 3 trial in which patients with moderate to severe AD with hand or foot involvement received subcutaneous dupilumab or placebo every 2&#xa0;weeks for 16&#xa0;weeks. An anchored MAIC was conducted using individual patient data (IPD) from DELTA 1/2 and aggregate published data from LIBERTY-AD-HAFT, with vehicle and placebo as the common anchor. IPD from patients with AHE as the primary subtype in DELTA 1/2 were weighted to match age, race, sex and baseline Hand Eczema Severity Index (HECSI) score in LIBERTY-AD-HAFT.</p> Results <p>LIBERTY-AD-HAFT included 133 patients (dupilumab, <i>n</i> = 67, placebo, <i>n</i> = 66) while DELTA 1/2 included 345 patients with AHE; the effective sample size after weighted matching was 201 (delgocitinib, <i>n</i> = 128, cream vehicle, <i>n</i> = 73). Anchor-adjusted odds ratios comparing delgocitinib versus dupilumab at week 16 were 1.1 (95% CI: 0.3, 3.4; <i>p</i> = 0.890) for Investigator’s Global Assessment for Chronic Hand Eczema / Hand and Foot Investigator’s Global Assessment score 0/1, 1.2 (95% CI: 0.4, 3.2; <i>p</i> = 0.773) for HECSI 75 and 1.3 (95% CI: 0.4, 4.9; <i>p</i> = 0.661) for HECSI 90 while response difference for HECSI percent improvement was 11.7% (95% CI: −9.2%, 32.7%; <i>p</i> = 0.273).</p> Conclusions <p>Topical delgocitinib and dupilumab in patients with AHE had comparable efficacy, with all results being numerically in favour of delgocitinib, although not statistically significant.</p> Clinical Trial Registration <p>NCT04871711, NCT04872101, NCT04417894.</p> Graphical Abstract <p></p>