Demographics and Baseline Disease Characteristics of Early Responders to Crisaborole for Atopic Dermatitis

included. The ISGA success endpoint also does not address itch, characterize the extent of AD skin involvement, or characterize other relevant patient-reported AD symptoms.¹¹ SPS addresses itch, which is considered a hallmark symptom of AD.¹² This analysis included ISGA and SPS responses, resulting in a more in-depth characterization of the effect of crisaborole on patients with AD.

The results of this post hoc analysis showed that early response to crisaborole can be a prognostic factor for ongoing response to treatment, highlighting the importance of early treatment adherence to improve treatment outcomes. AD is a chronic condition necessitating prolonged periods of treatment,^13,14 which may impact treatment adherence. Adherence to treatment, especially topical medications, is poor in chronic diseases.4 Differences in patient adherence could be a factor mediating differences in the response to topical crisaborole; however, >97% of patients in both phase 3 studies reported applying ≥95% of expected doses. Hence, treatment adherence was not an independent factor evaluated in this study. The early efficacy of crisaborole might have encouraged patients to adhere to treatment and might have improved patient accountability in treatment application,¹⁵ explaining why patients experienced continued improvement in AD severity and pruritus. Patient education focused on the association of early response to continued response can be used to highlight the importance of using crisaborole as indicated.

This was a post hoc analysis and therefore not specifically powered to show differences between groups. The analyses may be limited by unequal sample sizes between groups; however, there were trends in the data. Additionally, responder analyses in general are limited because the response cutoff may not be a consensus-defined threshold and the dichotomizing results into binary responses tend to result in statistical power loss in comparison with the original continuous variable analysis,¹⁶ which obscures smaller changes and continued improvement over time. However, this analysis used the common dichotomized endpoints of ISGA success and ISGA clear or almost clear. Additionally, this analysis defined SPS success as ≥1-point improvement, which is higher than the clinically important difference of 0.20.⁹ Finally, the results of the analysis were robust, even using binary responses. However, the results should be interpreted with caution because additional prospective studies are necessary confirm these results.

The results of this post hoc analysis suggest that patients aged <12 years who were white, had not received prior AD treatment, had disease duration ≤6.45 years, or did not concurrently use antihistamines were more likely to be early ISGA success and ISGA clear or almost clear responders. Patients who had moderate baseline disease by ISGA were more likely to be early ISGA success responders, whereas patients with mild baseline disease by ISGA and mild %BSA were more likely to be early ISGA clear or almost clear responders. Patients aged <12 years or who had moderate baseline disease by ISGA were more likely to be early responders based on SPS criteria. Additionally, patients who achieved ISGA success, ISGA clear or almost clear, or ≥1-point improvement in SPS early response at day 8 with crisaborole treatment were more likely to achieve continued response at day 29.

LFSG has been an investigator, consultant, or advisor for Pfizer Inc., AbbVie, Dermavant, Galderma, Incyte, LEO Pharma, Regeneron, and Sanofi. LT and CZ are employees and stockholders of Pfizer Inc. PS is an employee of Pfizer R&D UK Ltd., and stockholder of Pfizer Inc. SRF has received grant and consulting honoraria from Pfizer Inc., and is a consultant for and has received grants from Regeneron and Sanofi.

Editorial/medical writing support under the guidance of authors was provided by Juan Sanchez-Cortes, 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). This analysis was funded by Pfizer Inc.

Data Sharing Statement: Upon request, and subject to certain criteria, conditions and exceptions (see https://www.pfizer. com/science/clinical-trials/trial-data-and-results for more information), Pfizer will provide access to individual de-identified participant data from Pfizer-sponsored global interventional clinical studies conducted for medicines, vaccines and medical devices (1) for indications that have been approved in the US and/or EU or (2) in programs that have been terminated (ie, development for all indications has been discontinued). Pfizer will also consider requests for the protocol, data dictionary, and statistical analysis plan. Data may be requested from Pfizer trials 24 months after study completion. The de-identified participant data will be made available to researchers whose proposals meet the research criteria and other conditions, and for which an exception does not apply, via a secure portal. To gain access, data requestors must enter into a data access agreement with Pfizer.

1. Bieber T. Atopic dermatitis. N Engl J Med. 2008;358:1483-1494.
2. Blume-Peytavi U, Metz M. Atopic dermatitis in children: management of pruritus. J Eur Acad Dermatol Venereol. 2012;26 Suppl 6:2-8. 3. Drucker AM, Wang AR, Li WQ, et al. The burden of atopic dermatitis: summary of a report for the National Eczema Association. J Invest Dermatol. 2017;137:26-30.
4. Bass AM, Anderson KL, Feldman SR. Interventions to Increase treatment adherence in pediatric atopic dermatitis: a systematic review. J Clin Med. 2015;4:231-242.
5. Paller AS, Tom WL, Lebwohl MG, et al. Efficacy and safety of crisaborole