Tralokinumab Efficacy and Safety, with or without Topical Corticosteroids, in North American Adults with Moderate-to-Severe Atopic Dermatitis: A Subanalysis of Phase 3 Trials ECZTRA 1, 2, and 3

Abstract

Introduction: In pivotal phase 3 tralokinumab monotherapy (ECZTRA 1/2) and topical corticosteroid (TCS) combination (ECZTRA 3) trials in adults with moderate-to-severe atopic dermatitis (AD), tralokinumab significantly improved signs and symptoms of AD. Geographic region may impact treatment response due to potential differences in race and ethnicity, and based on findings in other therapy areas. Here, we evaluated the efficacy and safety of tralokinumab in the ECZTRA 1/2/3 North American population at week 16, as well as maintenance of responses over time, and compared these data side-by-side with those of the ECZTRA 1/2/3 non-North American population.

Methods: Primary endpoints were Investigator's Global Assessment score of 0 or 1 (IGA 0/1; clear or almost clear) or at least 75% improvement in Eczema Area and Severity Index (EASI-75) at week 16. At week 16, tralokinumab-treated IGA 0/1 or EASI-75 responders were re-randomized 2:2:1 to tralokinumab 300 mg q2w, or q4w, or placebo (ECZTRA 1/2) and 1:1 to tralokinumab 300 mg q2w or q4w (ECZTRA 3).

Results: Overall, 559/1596 (35%) and 160/380 (42.1%) patients randomized in ECZTRA 1/2 and ECZTRA 3 were from North America, respectively. At week 16, IGA 0/1 and EASI-75 response rates were greater with tralokinumab versus placebo in ECZTRA 1/2 (IGA 0/1: 25.3% vs 15.1%; 95% confidence interval [CI] 3.0, 17.3; p = 0.012; EASI-75, 40.1% vs 19.4%; 95% CI 12.6, 28.7; p < 0.001) and ECZTRA 3 (IGA 0/1, 40.0% vs 25.9%; 95% CI - 0.5, 28.3; p = 0.074; EASI-75: 58.1% vs 37.0%; 95% CI 4.9, 37.0; p = 0.012) and tralokinumab was well tolerated in the North American population. Patients with IGA 0/1 or EASI-75 response at week 16 demonstrated sustained responses at week 52 and week 32 in ECZTRA 1/2 and ECZTRA 3, respectively. Similar findings were observed in the non-North American trial populations.

Conclusions: Tralokinumab, with or without TCS, displayed similar efficacy and safety in patients with moderate-to-severe AD across the North American population, and was comparable to the non-North American population.

Clinical trial registration: NCT03131648 (registered 27-Apr-2017); NCT03160885 (registered 19-May-2017); NCT03363854 (registered 6-Dec-2017).

Keywords: Atopic dermatitis; Geographic region; North America; Patients; Tralokinumab.

© 2022. The Author(s).

Figures

Fig. 1

Achievement of a IGA score of 0/1 and b EASI-75 response in the ECZTRA 1/2 and ECZTRA 3 North American population at week 16. Patients who received rescue medication prior to week 16 or with missing data were considered non-responders. The Cochran–Mantel–Haenszel test was used to test risk difference, stratified by baseline IGA and study identification for ECZTRA 1 and ECZTRA 2, and baseline IGA for ECZTRA 3. Based on the full analysis set. *p < 0.05 vs placebo; ***p < 0.001 vs placebo. EASI-75 at least 75% improvement in Eczema Area and Severity Index, IGA Investigator’s Global Assessment, q2w every 2 weeks, TCS topical corticosteroid

Fig. 2

Cumulative amount of TCS used in the ECZTRA 3 North American population by visit, assuming no TCS used from non-returned tubes, initial treatment period, full analysis set. Data collected after permanent discontinuation of investigational medicinal product or initiation of rescue medication not included. Repeated measurements model: log[cumulative TCS amount + 1] (g) = Treatment*Week + Baseline IGA. *p < 0.05 vs tralokinumab. IGA Investigator’s Global Assessment, q2w every 2 weeks, SE standard error, TCS topical corticosteroid

Fig. 3

Achievement of EASI-90 in the ECZTRA 1/2 and ECZTRA 3 North American population at week 16. Patients who received rescue medication prior to week 16 or with missing data were considered non-responders. The Cochran–Mantel–Haenszel test was used to test risk difference, stratified by baseline IGA and study identification for ECZTRA 1/2, and by baseline IGA for ECZTRA 3. Based on the full analysis set. ***p < 0.001 vs placebo. EASI-90 at least 90% improvement in Eczema Area and Severity Index, IGA Investigator’s Global Assessment, q2w every 2 weeks, TCS topical corticosteroid

Fig. 4

Change in a SCORAD score, b DLQI, and c percentage change in weekly average worst daily pruritus NRS score in the ECZTRA 1/2 and ECZTRA 3 North American population at week 16. Data collected after permanent discontinuation of investigational medicinal product or initiation of rescue medication not included. Repeated measures model: ECZTRA 1/2, Change from baseline = Treatment*Week + Baseline*Week + Baseline IGA + Study Identification*Week; ECZTRA 3, Change from baseline = Treatment*Week + Baseline*Week + Baseline IGA. Based on the full analysis set. ***p < 0.001 vs placebo. DLQI Dermatology Life Quality Index, IGA Investigator’s Global Assessment, NRS numeric rating scale, q2w every 2 weeks, SCORAD SCORing Atopic Dermatitis, SE standard error, TCS topical corticosteroids

Fig. 5

Reduction in pruritus NRS ≥ 4 in the ECZTRA 1/2 and ECZTRA 3 North American population at week 16. Patients who received rescue medication prior to week 16 or with missing data were considered non-responders. The Cochran–Mantel–Haenszel test was used to test risk difference, stratified by baseline IGA and study identification for ECZTRA 1/2, and by baseline IGA for ECZTRA 3. Based on the full analysis set with a baseline pruritus NRS average of ≥ 4. **p < 0.01 vs placebo. IGA Investigator’s Global Assessment, NRS numeric rating scale, q2w every 2 weeks, TCS topical corticosteroid

Fig. 6

Efficacy outcomesa in patients achieving IGA 0/1 or EASI-75 response without rescue medication at week 16 in the ECZTRA 1/2 and ECZTRA 3 North American population, maintenance treatment period, full analysis set. aAt week 52 in ECZTRA 1/2 and week 32 in ECZTRA 3. Patients who received rescue medication or were transferred to open-label treatment or with missing data were considered non-responders. EASI-75 at least 75% improvement in Eczema Area and Severity Index, IGA Investigator’s Global Assessment, q2w every 2 weeks, TCS topical corticosteroid