TY - JOUR
T1 - Relationship Among Treatment, Pruritus, Investigator’s Static Global Assessment, and Quality of Life in Patients with Atopic Dermatitis
AU - Simpson, Eric L.
AU - Tom, Wynnis L.
AU - Bushmakin, Andrew G.
AU - Cappelleri, Joseph C.
AU - Yosipovitch, Gil
AU - Ständer, Sonja
AU - Luger, Thomas
AU - Sanders, Paul
AU - Gerber, Robert A.
AU - Myers, Daniela E.
N1 - Funding Information:
Medical writing support under the guidance of the authors was provided by Juan Sanchez-Cortes, PhD, and Stephanie Agbu, PhD, at ApotheCom, San Francisco, CA, USA, and was funded by Pfizer Inc., New York, NY, USA, in accordance with Good Publication Practice (GPP3) guidelines (Ann Intern Med. 2015;163:461–464).
Funding Information:
Eric L. Simpson has received grants from Pfizer Inc., Eli Lilly, Kyowa Kirin, LEO Pharma, Merck, and Regeneron and personal fees from Pfizer Inc., Bausch Health (Valeant), Dermira, Eli Lilly, Galderma, LEO Pharma, Menlo Therapeutics, Novartis, Regeneron, and Sanofi Genzyme. Sonja Ständer has served as an investigator for Dermasence, Galderma, Menlo Therapeutics, Novartis, and Trevi Therapeutics; a member of scientific advisory boards for Beiersdorf, Celgene, Galderma, Kiniksa, Menlo Therapeutics, Sienna Biopharmaceuticals, and Trevi Therapeutics; and a consultant for Bellus Health, Galderma, and Novartis. Gil Yosipovitch has served as a consultant and advisor for Pfizer Inc., Bellus Health, Eli Lilly, Galderma, Kiniksa, Menlo Therapeutics, Sanofi-Regeneron, Novartis, Trevi Therapeutics, and LEO Pharma; a principal investigator for Pfizer Inc., Kiniksa, LEO Pharma, Menlo Therapeutics, Novartis, Sun Pharma, and Vanda Pharmaceuticals; and a member of a scientific advisory board for Kiniksa. Andrew G. Bushmakin, Joseph C. Cappelleri, Paul Sanders, Daniela E. Myers, and Robert A. Gerber are employees and stockholders of Pfizer Inc. Thomas Luger has served as an investigator for Pfizer Inc., AbbVie, Celgene, Eli Lilly, LEO Pharma, Menlo Therapeutics, Novartis, and Sandoz; a member of scientific advisory boards for Pfizer Inc., AbbVie, Argenx, Celgene, Galderma, Eli Lilly, Janssen, La Roche-Posay, LEO Pharma, Menlo Therapeutics, Mylan/Meda AB, Novartis, Pierre Fabre, Piqur Therapeutics, Sandoz, Sanofi, and Symrise; and has received funding from Pfizer Inc., AbbVie, Celgene, Janssen, Merck Sharp & Dohme, Mylan/Meda AB, Novartis, and Wolfe Laboratories. Wynnis L. Tom has served as a principal investigator for Pfizer Inc., Incyte, Janssen, and Regeneron; and a safety committee member for LEO Pharma.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/4
Y1 - 2021/4
N2 - Introduction: The Investigator’s Static Global Assessment (ISGA) is a 5-point rating scale that is recommended by the US Food and Drug Administration for assessing the severity of atopic dermatitis (AD), and ISGA success is a widely used endpoint in AD clinical studies. In this study, we seek to interpret the relationship of ISGA with treatment, pruritus, and quality of life (QoL) by conducting post hoc analyses of pooled data from two phase 3 crisaborole studies. Methods: Patients aged ≥ 2 years with baseline ISGA of 2 (mild) or 3 (moderate) were randomly assigned 2:1 to receive crisaborole or vehicle for 28 days. Disease severity, pruritus severity, and QoL were assessed with the ISGA, Severity of Pruritus Scale (SPS), and Dermatology Life Quality Index (DLQI; patients aged ≥ 16 years), or Children’s Dermatology Life Quality Index (CDLQI; patients aged 2–15 years), respectively. The effect of treatment on ISGA and the relationship between ISGA and QoL were analyzed using a longitudinal repeated-measures model. The interrelationship between treatment, disease severity, pruritus, and QoL was analyzed with a mediation model. Results: Overall, 1522 patients (crisaborole, n = 1016; vehicle, n = 506) were included. Estimated longitudinal profiles indicated changes in ISGA by day 8 were large for crisaborole (effect size [ES]: − 0.68) and small for vehicle (ES: − 0.34). There was a direct relationship between ISGA and DLQI and CDLQI severity bands in the longitudinal repeated-measures model. For both QoL mediation models, treatment effects on QoL were mediated indirectly by reduction in pruritus (DLQI, 42.4%; CDLQI, 58.1%) and disease severity (DLQI, 12.2%; CDLQI, 33.1%). Conclusions: These post hoc analyses suggest that ISGA success is a clinically meaningful endpoint associated with reduction in the severity of pruritus and improvement in QoL.
AB - Introduction: The Investigator’s Static Global Assessment (ISGA) is a 5-point rating scale that is recommended by the US Food and Drug Administration for assessing the severity of atopic dermatitis (AD), and ISGA success is a widely used endpoint in AD clinical studies. In this study, we seek to interpret the relationship of ISGA with treatment, pruritus, and quality of life (QoL) by conducting post hoc analyses of pooled data from two phase 3 crisaborole studies. Methods: Patients aged ≥ 2 years with baseline ISGA of 2 (mild) or 3 (moderate) were randomly assigned 2:1 to receive crisaborole or vehicle for 28 days. Disease severity, pruritus severity, and QoL were assessed with the ISGA, Severity of Pruritus Scale (SPS), and Dermatology Life Quality Index (DLQI; patients aged ≥ 16 years), or Children’s Dermatology Life Quality Index (CDLQI; patients aged 2–15 years), respectively. The effect of treatment on ISGA and the relationship between ISGA and QoL were analyzed using a longitudinal repeated-measures model. The interrelationship between treatment, disease severity, pruritus, and QoL was analyzed with a mediation model. Results: Overall, 1522 patients (crisaborole, n = 1016; vehicle, n = 506) were included. Estimated longitudinal profiles indicated changes in ISGA by day 8 were large for crisaborole (effect size [ES]: − 0.68) and small for vehicle (ES: − 0.34). There was a direct relationship between ISGA and DLQI and CDLQI severity bands in the longitudinal repeated-measures model. For both QoL mediation models, treatment effects on QoL were mediated indirectly by reduction in pruritus (DLQI, 42.4%; CDLQI, 58.1%) and disease severity (DLQI, 12.2%; CDLQI, 33.1%). Conclusions: These post hoc analyses suggest that ISGA success is a clinically meaningful endpoint associated with reduction in the severity of pruritus and improvement in QoL.
KW - Atopic dermatitis
KW - Children’s Dermatology Life Quality Index
KW - Crisaborole
KW - Dermatology Life Quality Index
KW - Investigator’s Static Global Assessment
KW - Pruritus
KW - Quality of life
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UR - http://www.scopus.com/inward/citedby.url?scp=85102382834&partnerID=8YFLogxK
U2 - 10.1007/s13555-021-00506-y
DO - 10.1007/s13555-021-00506-y
M3 - Article
AN - SCOPUS:85102382834
VL - 11
SP - 587
EP - 598
JO - Dermatology and Therapy
JF - Dermatology and Therapy
SN - 2190-9172
IS - 2
ER -