Translating the Investigator's Static Global Assessment to the Eczema Area and Severity Index in Studies of Crisaborole for Atopic Dermatitis

Jacob P Thyssen, Chuanbo Zang, Maureen P Neary, Andrew G Bushmakin, Joseph C Cappelleri, Amy Cha, Christopher Russo, Thomas A Luger, Jacob P Thyssen, Chuanbo Zang, Maureen P Neary, Andrew G Bushmakin, Joseph C Cappelleri, Amy Cha, Christopher Russo, Thomas A Luger

Abstract

Introduction: Atopic dermatitis (AD) severity was measured in two phase 3 US studies of crisaborole ointment, 2%, in patients aged ≥ 2 years using the Investigator's Static Global Assessment (ISGA), an FDA-recommended scale. Eczema Area and Severity Index (EASI) is a validated scale used globally to assess AD severity in clinical trials. The objective of this study is to aid interpretability of ISGA by translating ISGA scores to EASI scores.

Methods: ISGA was mapped to EASI using published EASI severity strata by Chopra et al. and Leshem et al. and pooled data from phase 3 trials CrisADe CORE 1 and CORE 2, which evaluated crisaborole in patients aged ≥ 2 years with mild-to-moderate AD (crisaborole, n = 1016; vehicle, n = 506). Least squares mean (LSM) percentage change from baseline (%CFB) in EASI and proportion of patients with 50%, 75%, and 90% improvement (EASI-50, EASI-75, and EASI-90, respectively) on day 29 were computed for mapped EASI. The relationship between changes in ISGA and changes in EASI was assessed using data from three abrocitinib trials.

Results: ISGA was mapped to EASI using 70,000 random simulations. LSM (standard error) for %CFB in mapped EASI at day 29 (crisaborole versus vehicle) was -26.3% (17) versus 45.2% (35) (P = 0.0671) using Chopra strata and -43.1% (4.6) versus -5.2% (8.4) (P < 0.0001) using Leshem strata. EASI-50, EASI-75, and EASI-90 rates were 72.1% versus 57.6%, 63.0% versus 47.8%, and 55.0% versus 40.1%, respectively, using Chopra strata (P < 0.0001 for each difference). These rates were 68.8% versus 54.0%, 54.8% versus 40.5%, and 38.9% versus 27.2%, respectively (P < 0.0001 for each difference) using Leshem strata. Mean two-point improvement in ISGA was comparable to EASI-90.

Conclusion: Mapped EASI results were consistent with ISGA results in crisaborole phase 3 trials. Simulation methodologies yielded consistent results and may aid in interpretability of ISGA across clinical studies.

Trial registration: ClinicalTrials.gov identifier: NCT02118766, NCT02118792.

Keywords: Atopic dermatitis; Clinical trial; Crisaborole; Eczema Area and Severity Index; Investigator’s Static Global Assessment; Severity strata.

Figures

Fig. 1
Fig. 1
Generated day 29 outcomes for a EASI-50, b EASI-75, and c EASI-90. EASI Eczema Area and Severity Index
Fig. 2
Fig. 2
Mean change in I(S)GA by percentage change in EASI at week 12. EASI Eczema Area and Severity Index, I(S)GA Investigator’s (Static) Global Assessment. Intersection of the red lines indicates that a mean two-point improvement in I(S)GA corresponds to 90% improvement in EASI

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Source: PubMed

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