Abstract / Summary
Both tralokinumab and dupilumab have shown efficacy in atopic dermatitis (AD) with moderate-to-severe hand involvement in double-blind phase 3 trials. As there are no head-to-head studies of tralokinumab and dupilumab, an anchored matching-adjusted indirect comparison (MAIC) was conducted. In the ADHAND trial, adults with AD with moderate-to-severe hand involvement were randomised to tralokinumab 300 mg or placebo every 2 weeks for 16 weeks. In the LIBERTY-AD-HAFT trial, adults and adolescents (≥ 12 years) with moderate-to-severe AD with hand and/or foot involvement were randomised to dupilumab 300 mg or placebo every 2 weeks for 16 weeks. An anchored MAIC was conducted using individual patient data from ADHAND weighted to match aggregate data for age, sex, race, and baseline Hand Eczema Severity Index (HECSI) score from LIBERTY-AD-HAFT, with placebo as the common anchor. Endpoints compared at week 16 were proportions of patients with Investigator’s Global Assessment scores of 0/1, HECSI-75 and HECSI-90, and percent reductions in HECSI and the Routine Activity Impairment domain of the Work Productivity and Activity Index. Reductions in itch and pain and proportions of patients with ≥ 4-point itch improvement were also compared. LIBERTY-AD-HAFT included 133 patients (dupilumab, n = 67, placebo, n = 66) while ADHAND included 235 patients (tralokinumab, n = 156; placebo, n = 79). The effective sample size after matching was 99 (tralokinumab, n = 76, placebo, n = 23). Anchor-adjusted relative treatment differences significantly favoured tralokinumab compared with dupilumab for the proportions of patients achieving HECSI-90 (17.5% [95% CI 0.8, 34.2]; p = 0.040) and decrease in percent routine activity impairment (16.0% [95% CI 4.8, 27.1]; p = 0.005). Relative differences for other endpoints favoured tralokinumab over dupilumab but were not significantly different between treatments. In this anchored MAIC, tralokinumab was associated with a higher placebo-adjusted response than dupilumab, with a higher proportion achieving HECSI-90, and a significantly greater improvement in ability to perform regular daily activities versus dupilumab. Other endpoints were numerically in favour of tralokinumab. Graphical abstract and video abstract available for this article. NCT05958407, NCT04417894. Tralokinumab and dupilumab are both effective treatments for atopic dermatitis of the hands. However, they have not been compared with one another in a clinical trial. Anchored matching-adjusted indirect comparison is a statistical method used to compare two treatments that have not been directly tested against each other. This method uses data from two different but similarly designed studies which both include a group of patients receiving the same treatment, such as placebo, to allow comparison across studies. In the LIBERTY-AD-HAFT clinical trial, 133 adults and adolescents with moderate-to-severe atopic dermatitis with hand and/or foot involvement were randomised to receive treatment with dupilumab 300 mg or placebo every 2 weeks for 16 weeks. In the ADHAND clinical trial, adults with atopic dermatitis with moderate-to-severe hand involvement were randomised to tralokinumab 300 mg or placebo every 2 weeks for 16 weeks. Characteristics of patients in the ADHAND trial were matched to those of patients in the LIBERTY-AD-HAFT trial, which resulted in a group of 99 patients similar in age, sex, race, and disease severity. After 16 weeks of treatment, more patients achieved a 90% or greater improvement in the Hand Eczema Severity Index score with tralokinumab (27%) than with dupilumab (9.5%), with a statistically significant 17.5% difference between treatments. This indicates a deeper response to treatment with tralokinumab than dupilumab. Patients treated with tralokinumab also had a significantly greater improvement in the ability to perform regular daily activities compared with dupilumab. Improvements in other measurements of efficacy (including itch and pain) also favoured tralokinumab over dupilumab but were not statistically significant.