Dataset Information

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

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.

SUBMITTER: Thyssen JP

PROVIDER: S-EPMC8163913 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMultiple clinician-reported outcome measures exist for atopic dermatitis (AD) severity. However, there is no gold standard for use in clinical practice.ObjectivesTo determine the measurement properties of the product of validated Investigator's Global Assessment for AD (vIGA) and body surface area (BSA) overall or divided into six categories (cBSA: 0%/0.1, <10%/10, <30%/30, <50%/50, <70%/70 and <90%/90-100%) and compare with other clinician-reported and patient-reported outcomes in adults and children with AD.MethodsWe performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 653).ResultsvIGA*BSA and vIGA*cBSA had good convergent validity with BSA (Spearman's ρ = 0.97 and 0.93), eczema area and severity index (ρ = 0.94 and 0.92), and objective SCORAD (ρ = 0.88 and 0.89); and weak-to-good convergent validity with Numeric Rating Scale average itch (ρ = 0.22 and 0.22) and worst itch (ρ = 0.27 and 0.28), Patient-Oriented Eczema Measure (ρ = 0.44 and 0.43), Dermatology Life Quality Index (ρ = 0.48 and 0.49), ItchyQOL (ρ = 0.45 and 0.46), PROMIS Sleep Disturbance (ρ = 0.46 and 0.37) and sleep-related impairment (ρ = 0.31 and 0.31) in adults and/or children; very good discriminant validity for physician-reported global AD severity; good responsiveness to change of severity of AD and itch; and good reliability (intraclass correlation coefficient [95% confidence interval]: 0.72 [0.60-0.81] and 0.74 [0.62-0.82]) with no floor or ceiling effects. Thresholds for interpretability bands and clinically important difference were established.ConclusionsvIGA*BSA and vIGA*cBSA scores showed good convergent and discriminant validity, reliability, responsiveness and interpretability in adults and children with AD, and were feasible for use in clinical practice. vIGA*BSA and vIGA*cBSA had slightly lower convergent validity than EASI or objective SCORAD, but might be more efficient to collect and score.

Project description:Background: Crisaborole is a nonsteroidal anti-inflammatory phosphodiesterase 4 inhibitor that is approved for the treatment of patients with mild-to-moderate atopic dermatitis (AD); however, the efficacy and safety of crisaborole in patients with AD and other atopic comorbidities have not been investigated. Objective: This post hoc pooled analysis of the pivotal phase III studies (CrisADe CORE 1 and CORE 2) assessed the efficacy and safety of crisaborole versus vehicle in patients aged ≥ 2 years with mild-to-moderate AD and other atopic comorbidities. Methods: Patients with mild-to-moderate AD and a medical history of asthma, allergic rhinitis, or food allergies were identified. Efficacy assessments included the proportion of patients who achieved Investigator's Static Global Assessment (ISGA) success at day 29, ISGA clear or almost clear at day 29, and improvement in the Severity of Pruritus Scale score at week 4. Safety was assessed via treatment-emergent adverse events (TEAEs). Results: This analysis included 1522 patients (crisaborole, 1016; vehicle, 506); 26.2, 15.9, and 16.5% had a medical history of asthma, allergic rhinitis, and food allergies, respectively. The mean age was 12.2 years. A significantly greater proportion of patients treated with crisaborole achieved ISGA success at day 29 compared with patients treated with vehicle for most subgroups analyzed. Furthermore, a significantly greater proportion of patients treated with crisaborole achieved ISGA clear or almost clear at day 29 across all subgroups and demonstrated improvement in the Severity of Pruritus Scale score at week 4 versus patients treated with vehicle in most of the subgroups. Overall, most TEAEs were mild or moderate in severity; the most common treatment-related TEAE in patients with atopic comorbidities was application-site pain (crisaborole, 5.1%; vehicle, 1.7%). Conclusion: Crisaborole was efficacious and well tolerated in patients with mild-to-moderate AD and other atopic comorbidities, which suggested that crisaborole should be considered for the management of AD in this population. Clinical Trials NCT02118766 (CrisADe CORE 1) and NCT02118792 (CrisADe CORE 2), <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">www.clinicaltrials.gov</ext-link>.