IGAxBSA composite for assessing disease severity and response in patients with atopic dermatitis

A S Paller, J K L Tan, J Bagel, A B Rossi, B Shumel, H Zhang, A Abramova, A S Paller, J K L Tan, J Bagel, A B Rossi, B Shumel, H Zhang, A Abramova

Abstract

Background: Accurate assessment of atopic dermatitis (AD) severity is critical when initiating and monitoring therapy. Use of existing research tools such as the Eczema Area and Severity Index (EASI) and Scoring Atopic Dermatitis (SCORAD) is complex and time-consuming in clinical practice. A previous analysis found the product of validated Investigator's Global Assessment (vIGA) and affected body surface area (BSA) to be an accurate and practical tool for routine assessment of paediatric AD.

Objective: To evaluate the IGAxBSA composite as an alternative to EASI or SCORAD for assessment of AD disease severity and disease responsiveness.

Methods: The relationship between IGAxBSA, EASI and SCORAD was assessed in a post hoc analysis of pooled data from the dupilumab clinical trial programme in adult and paediatric patients with moderate-to-severe AD who had received dupilumab or placebo, with or without topical corticosteroids (TCS). The trials are registered at ClinicalTrials.gov and EudraCT: LIBERTY AD SOLO 1 (NCT02277743, 2014-001198-15), LIBERTY AD SOLO 2 (NCT02277769, 2014-002619-40), LIBERTY AD SOLO-CONTINUE (NCT02395133, 2014-003384-38), LIBERTY AD CHRONOS (NCT02260986, 2013-003254-24), LIBERTY AD CAFÉ (NCT02755649, 2015-002653-35), LIBERTY AD ADOL (NCT03054428, 2015-004458-16), LIBERTY AD PEDS (NCT03345914, 2016-004997-16), LIBERTY AD OLE (NCT01949311, 2013-001449-15) and LIBERTY AD PEDS OLE (NCT02612454, 2015-001396-40).

Results: Using datapoints from pooled dupilumab randomized controlled trials (n = 3473) and open-label extension trials (n = 3045), we found that IGAxBSA correlated well with EASI and SCORAD, irrespective of treatment group and race (white, Asian, black). IGAxBSA correlated better with objective measures (EASI, SCORAD) than with patient- or caregiver-reported subjective measures. IGAxBSA correlated strongly with EASI and SCORAD in assessing disease change over time (r = 0·90, r = 0·76, respectively; P < 0·0001), and concordance between IGAxBSA-50/75/90 and EASI-50/75/90 was excellent (88-94%).

Conclusions: IGAxBSA is a valid alternative for assessment of AD disease severity and response over time, compared with EASI or SCORAD in patients with AD, irrespective of race.

© 2021 Regeneron. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

Figures

Figure 1
Figure 1
(a) Scatter plot of the correlation of disease severity metrics IGAxBSA vs. Eczema Area and Severity Index (EASI), all patients pooled (n = 36 657). Spearman correlation = 0·95, P < 0·0001. (b) Scatter plot of the correlation of disease severity metrics IGAxBSA vs. EASI by severity, all patients pooled (n = 36 657). Spearman correlation = 0·95, P < 0·0001. BSA, body surface area; IGA, Investigator’s Global Assessment.
Figure 2
Figure 2
Scatter plot of the correlation of disease severity metrics IGAxBSA vs. Eczema Area and Severity Index (EASI), all patients pooled. (a) White, n = 25 464; Spearman correlation = 0·96, P < 0·0001; (b) black, n = 2380; Spearman correlation = 0·95, P < 0·0001; (c) Asian, n = 7664; Spearman correlation = 0·94, P < 0·0001. BSA, body surface area; IGA, Investigator’s Global Assessment.
Figure 3
Figure 3
Concordance of IGAxBSA vs. EASI: patients in randomized controlled trials. (a) Placebo‐treated patients, with or without topical corticosteroids (TCS); (b) dupilumab‐treated patients, with or without TCS. BSA, body surface area; EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment. Agreement between IGAxBSA and EASI scores was further assessed based on intraclass correlation coefficients and response concordance rates, using improvements from baseline of 50%, 75% and 90% as the response thresholds in both scales. Concordance was calculated as (number of patients without EASI response and without IGAxBSA response) + (number of patients with EASI response and with IGAxBSA response) / the total number of patients with sufficient data for evaluation. Patients were considered overrated if response was achieved based on IGAxBSA, but not achieved based on EASI. Patients were considered underrated if response was achieved based on EASI, but not achieved based on IGAxBSA. Note that the end of treatment visit for SOLO 1&2, CAFÉ, PEDs and ADOL is week 16, end of treatment visit for SOLO‐CONTINUE is week 36, and end of treatment visit for CHRONOS is week 52.
Figure 4
Figure 4
Scatter plot of the correlation of disease severity metrics IGAxBSA vs. Scoring Atopic Dermatitis (SCORAD), all patients pooled (n = 36 547). Spearman correlation = 0·89, P < 0·0001. BSA, body surface area; IGA, Investigator’s Global Assessment.
Figure 5
Figure 5
Scatter plot of the correlation of disease severity metrics IGAxBSA vs. Scoring Atopic Dermatitis (SCORAD), all patients pooled. (a) White, n = 25 364; Spearman correlation = 0·90, P < 0·0001; (b) black, n = 2378; Spearman correlation = 0·87, P < 0·0001; (c) Asian, n = 7657; Spearman correlation = 0·88, P < 0·0001. BSA, body surface area; IGA, Investigator’s Global Assessment.
Figure 6
Figure 6
Concordance of IGAxBSA vs. Scoring Atopic Dermatitis (SCORAD): patients in randomized controlled trials. (a) Placebo‐treated patients, (b) dupilumab‐treated patients. BSA, body surface area; IGA, Investigator’s Global Assessment. Agreement between IGAxBSA and SCORAD scores was further assessed based on intraclass correlation coefficients and response concordance rates, using improvements from baseline of 50%, 75% and 90% as the response thresholds in both scales. Concordance was calculated as (number of patients without SCORAD response and without IGAxBSA response) + (number of patients with SCORAD response and with IGAxBSA response) / the total number of patients with sufficient data for evaluation. Patients were considered overrated if response was achieved based on IGAxBSA, but not achieved based on SCORAD. Patients were considered underrated if response was achieved based on SCORAD, but not achieved based on IGAxBSA. Note that the end of treatment visit for SOLO 1&2, CAFÉ, PEDs and ADOL is week 16, end of treatment visit for SOLO‐CONTINUE is week 36, and end of treatment visit for CHRONOS is week 52.
Figure 7
Figure 7
(a) Scatter plot of the correlation of disease severity metrics IGAxBSA vs. Eczema Area and Severity Index (EASI), change from baseline to end of treatment, randomized controlled trial (RCT) patients pooled, n = 3267. Spearman correlation = 0·90, P < 0·0001. (b) Scatter plot of the correlation of disease severity metrics IGAxBSA vs. Scoring Atopic Dermatitis, change from baseline to end of treatment, RCT patients pooled, n = 3250. Spearman correlation = 0·76, P < 0·0001. BSA, body surface area; IGA, Investigator’s Global Assessment. Note that the end of treatment visit for SOLO 1&2, CAFÉ, PEDs and ADOL is week 16, end of treatment visit for SOLO‐CONTINUE is week 36, and end of treatment visit for CHRONOS is week 52.
Figure 8
Figure 8
Heatmap correlation between disease measures in pooled studies (randomized controlled trials and open‐label extensions; Spearman correlations) from low to high (0–1), all correlations significant (P < 0·0001). Total N = 6518. BSA, body surface area; CDLQI, Children’s Dermatology Life Quality Index; DLQI, Dermatology Life Quality Index; EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment; NRS, numerical rating scale; o‐SCORAD, objective Scoring Atopic Dermatitis; POEM, Patient‐Oriented Eczema Measure; SCORAD, Scoring Atopic Dermatitis.

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