A Mini Review of the Impact of Baseline Disease Severity on Clinical Outcomes: Should We Compare Atopic Dermatitis Clinical Trials?

Abstract

Based on clinical trials of systemic treatments in adults with moderate-to-severe atopic dermatitis (AD) reported between 2014 and 2023, we used linear regression to investigate relationships between baseline Eczema Area and Severity Index (EASI) scores and (1) study start date, (2) EASI response, and (3) rescue medication rates. Analysis 1 was conducted with all patients from monotherapy and combination therapy trials; analyses 2 and 3 used monotherapy trial placebo arms. Across 32 trials with a baseline inclusion criterion of EASI ≥ 16, baseline mean EASI scores decreased with study start date. The lowest and highest baseline mean EASI scores were 25.1 and 33.6 (median 21.1 and 30.5), reported for the WW001 Phase 2 trial of rademikibart (formerly CBP-201; start date, July 2020) and the SOLO1 Phase 3 trial of dupilumab (start date, December 2014), respectively. In placebo arms, lower baseline EASI scores tended to be associated with greater percent reductions in EASI scores at Week 16 and less rescue medication usage. The WW001 trial placebo arm had the lowest baseline EASI score (mean 25.2; median 22.1), lowest rescue medication rate (14.3%), and a large reduction in least squares mean EASI scores (- 39.7%) at Week 16. In summary, baseline mean EASI scores have decreased across clinical trials conducted during the last decade. Less severe AD at baseline tended to be associated with greater placebo response and less use of rescue medications in placebo arms. Intertrial differences in variables, such as baseline AD severity, limit the validity of indirectly comparing clinical trials.

Keywords: Atopic dermatitis; Baseline severity; CBP-201; Clinical trial comparison; IL-13; IL-4; JAK inhibitor; Placebo response; Rademikibart.

Fig. 1

Baseline mean EASI scores for the overall populations in AD clinical trials with an EASI inclusion criterion of ≥ 16 at baseline. If mean values and study start dates were not available in published papers, they were obtained from clinicaltrials.gov. Abro abrocitinib, Ast astegolimab, AD atopic dermatitis, Bar baricitinib, Combo combination therapy, CS topical corticosteroid, Dupi dupilumab, EASI Eczema Area and Severity Index, Etra etrasimod; Lebri, lebrikizumab, Mono monotherapy, Nemo nemolizumab, Ph phase, Rade rademikibart, Ris risankizumab, Roca rocatinlimab, Tez Tezepelumab, Tralo tralokinumab, Upa upadacitinib

Fig. 2

EASI scores at baseline vs percent reductions in EASI scores at Week 16 in placebo arms in AD clinical trials of systemic monotherapies. If mean values were not available in published papers, they were obtained from clinicaltrials.gov. Ast astegolimab, AD atopic dermatitis, Bar baricitinib, Dupi dupilumab, EASI Eczema Area and Severity Index, Lebri lebrikizumab, Nemo nemolizumab, Ph phase, Rade rademikibart, Tez tezepelumab, Tralo tralokinumab, Upa upadacitinib

Fig. 3

EASI scores at baseline vs rescue medication usage in placebo arms in AD clinical trials of systemic monotherapies with 16-week treatment periods. If mean values were not available in published papers, they were obtained from clinicaltrials.gov. Clinical trials were included if they allowed use of rescue medication and reported rescue medication rates. AD atopic dermatitis, Bar baricitinib, Dupi dupilumab, EASI Eczema Area and Severity Index, Lebri lebrikizumab, Ph phase, Rade rademikibart, Tralo tralokinumab, Upa upadacitinib