Assessing clinical response and defining minimal disease activity in plaque psoriasis with the Physician Global Assessment and body surface area (PGA × BSA) composite tool: An analysis of apremilast phase 3 ESTEEM data
Authors: Alice B. Gottlieb, Joseph F. Merola, Rongdean Chen, Eugenia Levi, Kristina Callis Duffin
Journal: Journal of the American Academy of Dermatology (2017)

To the Editor: The product of Physician Global Assessment (PGA) and body surface area (BSA) (PGA × BSA) is a simple tool for assessing psoriasis severity and clinical response to treatment. PGA × BSA scores have demonstrated sensitivity to therapeutic change and concordance with Psoriasis Area and Severity Index (PASI)-based clinical response.1Walsh J.A. McFadden M. Woodcock J. et al.Product of the Physician Global Assessment and body surface area: a simple static measure of psoriasis severity in a longitudinal cohort.J Am Acad Dermatol. 2013; 69: 931-937Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar, 2Callis Duffin K. Papp K.A. Bagel J. Levi E. Chen R. Gottlieb A.B. Evaluation of the Physician Global Assessment and body surface area composite tool for assessing psoriasis response to apremilast therapy: results from ESTEEM 1 and ESTEEM 2.J Drugs Dermatol. 2017; 16: 147-153PubMed Google Scholar We report the results of a post hoc analysis of data from the ESTEEM 1 and 2 trials that defines bands and minimal disease activity (MDA) for the PGA × BSA scale using accepted PASI and Dermatology Life Quality Index (DLQI) response categories as anchors. The analyses were performed with week 16 data, as observed and sufficient for evaluation with no imputation for missing values, from 836 patients who were randomized to receive apremilast, 30 mg twice daily, at baseline in ESTEEM 1 (N = 562) and ESTEEM 2 (N = 274).3Papp K. Reich K. Leonardi C.L. et al.Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM 1]).J Am Acad Dermatol. 2015; 73: 37-49Abstract Full Text Full Text PDF PubMed Scopus (398) Google Scholar, 4Paul C. Cather J. Gooderham M. et al.Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate to severe plaque psoriasis over 52 weeks: a phase III, randomized, controlled trial (ESTEEM 2).Br J Dermatol. 2015; 173: 1387-1399Crossref PubMed Scopus (309) Google Scholar Detailed study design and assessment procedures have been published.2Callis Duffin K. Papp K.A. Bagel J. Levi E. Chen R. Gottlieb A.B. Evaluation of the Physician Global Assessment and body surface area composite tool for assessing psoriasis response to apremilast therapy: results from ESTEEM 1 and ESTEEM 2.J Drugs Dermatol. 2017; 16: 147-153PubMed Google Scholar, 3Papp K. Reich K. Leonardi C.L. et al.Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM 1]).J Am Acad Dermatol. 2015; 73: 37-49Abstract Full Text Full Text PDF PubMed Scopus (398) Google Scholar, 4Paul C. Cather J. Gooderham M. et al.Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate to severe plaque psoriasis over 52 weeks: a phase III, randomized, controlled trial (ESTEEM 2).Br J Dermatol. 2015; 173: 1387-1399Crossref PubMed Scopus (309) Google Scholar Patients provided written informed consent before study-related procedures were performed, and the protocol and consent were approved by institutional review boards or ethics committees at all investigational sites. The studies were conducted in accordance with the principles of Good Clinical Practice and the Declaration of Helsinki. Mean percent change in PGA × BSA was significantly correlated with percent change in PASI (r range, 0.915-0.943; all P < .001) and mean change in DLQI (r range, 0.303-0.407; all P < .008), regardless of baseline PASI score category (12-19 or ≥20). The PGA × BSA absolute median and interquartile range (IQR) scores observed in subgroups of patients who achieved PASI and/or DLQI “anchor” responses (eg, PASI 90 or PASI 90 plus DLQI score of 0 or 1 [PASI 90+DLQI 0 or 1]) at week 16 are illustrated in Fig 1. With increasing levels of clinical improvement as defined by PASI or PASI/DLQI response, median (IQR) PGA × BSA scores decreased in a distinct stepwise fashion. To establish reproducibility of the proposed bands, the defined PGA × BSA IQR score ranges were subsequently used as treatment target values, and response rates were determined. These PGA × BSA response rates were generally similar to those observed with the corresponding PASI or PASI/DLQI anchors, particularly for the most widely achieved PASI response categories (PASI 50 to <75 and PASI 75 to <90) (Fig 2). Discrepant response rates, however, were observed for the proposed PGA × BSA MDA criterion of 3 or lower versus the corresponding anchor of PASI 90+DLQI 0 or 1 for ESTEEM 1 (20.2% vs 6.4%) and ESTEEM 2 (21.1% vs 8.0%) (Fig 2). Additional ad hoc analyses demonstrated that when a PGA × BSA MDA of 1 or lower or 1.5 or lower was used, the response rates better aligned with those for PASI 90 and PASI 90+DLQI 0 or 1. The proposed PGA × BSA MDA score of 1.0 or lower may be appropriate for patients who wish to achieve complete or nearly complete skin clearance, whereas higher PGA × BSA bands may be appropriate for patients with psoriasis who report good quality of life despite some remaining skin involvement. In sum, these findings show that the PGA × BSA composite tool can be used to measure clinical response and to assess MDA in patients with psoriasis. The current post hoc banding analysis, using PASI and DLQI response categories as clinically relevant “anchors,” identified PGA × BSA bands that provide clinically useful criteria for treat-to-target strategies. Because ESTEEM enrolled only patients with moderate to severe plaque psoriasis, the criteria require further investigation in patients with all levels of psoriasis severity. Recently, the PGA × BSA composite tool was successfully used to assess efficacy of apremilast in patients with moderate disease (BSA 5% to 10%).5Strober B, Bagel J, Lebwohl M, et al. Efficacy and safety of apremilast in patients with moderate plaque psoriasis (UNVEIL phase IV study). Poster presented at: 75th Annual Meeting of the American Academy of Dermatology; March 3-7, 2017; Orlando, FL.Google Scholar The authors received editorial support in preparation of the Research Letter from Karen Dougherty, PhD, and Kristin E. Larsen, PhD, of Peloton Advantage, LLC, funded by Celgene Corporation. The authors, however, directed and are fully responsible for all content and editorial decisions for this Research Letter.