Attrition of topical calcineurin inhibitor use over time in patients with atopic dermatitis

Abstract

To the Editor: The American Academy of Dermatology's guidelines recommend topical calcineurin inhibitors (TCIs) for acute and maintenance treatment of atopic dermatitis (AD).1Eichenfield L.F. Tom W.L. Berger T.G. et al.Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies.J Am Acad Dermatol. 2014; 71: 116-132https://doi.org/10.1016/j.jaad.2014.03.023Abstract Full Text Full Text PDF PubMed Scopus (744) Google Scholar TCIs have minimal risk of skin atrophy and discoloration, can reduce the need for topical corticosteroids (TCSs), and have an excellent safety profile, with no evidence of clinically meaningful increase in malignancy rates relative to malignancy rates in the general population in long-term follow-up studies.1Eichenfield L.F. Tom W.L. Berger T.G. et al.Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies.J Am Acad Dermatol. 2014; 71: 116-132https://doi.org/10.1016/j.jaad.2014.03.023Abstract Full Text Full Text PDF PubMed Scopus (744) Google Scholar,2Lam M. Zhu J.W. Tadrous M. Drucker A.M. Association between topical calcineurin inhibitor use and risk of cancer, including lymphoma, keratinocyte carcinoma, and melanoma: a systematic review and meta-analysis.JAMA Dermatol. 2021; 157: 549-558https://doi.org/10.1001/jamadermatol.2021.0345Crossref PubMed Scopus (13) Google Scholar Given these benefits, one would expect TCIs to be preferable to TCSs, particularly in sensitive areas. However, although they are now generic, TCIs can be more expensive and difficult to obtain than TCSs. In addition, little research has been done on the use patterns of TCIs in patients with AD. Therefore, we sought to evaluate the use of TCIs compared with the use of TCSs for AD in clinically sensitive areas.We conducted a retrospective analysis using the Pediatric Eczema Elective Registry's data set, a previously described longitudinal cohort of US individuals with mild-to-moderate AD.3Margolis J.S. Abuabara K. Bilker W. Hoffstad O. Margolis D.J. Persistence of mild to moderate atopic dermatitis.JAMA Dermatol. 2014; 150: 593-600https://doi.org/10.1001/jamadermatol.2013.10271Crossref PubMed Scopus (186) Google Scholar The individuals were required to use pimecrolimus for ≥6 weeks out of the 6 months preceding enrollment. At 6-month intervals for up to 10 years, the individuals reported the presence and location of the disease; use of Elidel cream, Protopic ointment, and TCSs; and location of treatment application. The individuals were not required to continue pimecrolimus after enrollment. In the study, no medications were provided to the study subjects; the sponsor had no role in treatment decisions.We evaluated surveys reporting a concurrent acute-to-chronic AD rash and medication use at particular sites over time. Proportional odds logistic regression models were used to evaluate the association between year of follow-up and likelihood of using TCIs. The models were adjusted for ethnicity, sex, and income; the outcome variable was the difference between TCI and steroid use, arranged on an ordinal scale. Implementation was done using the “polr” function (package MASS 7.3-54) in R 3.6.1.Eight thousand fifteen subjects completed 82,591 surveys, representing >40,000 person-years of follow-up. During year 1, 53% of the surveys reported a rash on the face; this decreased to 31% by year 10. Similar trends were observed for other rash locations. The likelihood of using TCIs decreased over time (Figs 1 and 2). These trends persisted after adjusting for race, income, and sex (rash on the face: odds ratio [95% CI], 0.880 [0.874-0.886], P < .001; upper extremities: odds ratio [95% CI], 0.895 [0.889-0.901], P < .001; and lower extremities: odds ratio [95% CI], 0.897 [0.891-0.903], P < .001).Fig 2Results of proportional odds logistic regression model for rash on the face alone, demonstrating the probability of TCI use without steroid use and the probability of steroid use without TCI use. The probability of using TCIs without steroids on the face decreases with a longer duration of follow-up. In contrast, the probability of using steroids without TCIs on the face increases with increasing duration of follow-up. The shaded regions represent 95% CIs. TCI, Topical calcineurin inhibitor.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Despite the potential clinical value of TCIs for AD, particularly on sites such as the face, TCI use decreased over time among the Pediatric Eczema Elective Registry individuals. Shift from TCIs to TCSs was observed across both the sensitive sites and other locations, suggesting that rash location did not influence treatment choice. This shift persisted after adjusting for sociodemographic factors. Difficulties with respect to coverage and cost, TCI tolerability, or patient and clinician preferences may have been responsible for these observed trends. The Pediatric Eczema Elective Registry study only provides information on patient practices and does not allow us to differentiate between these possibilities. Although our findings suggest that TCIs are underused among individuals with AD, particularly for sensitive sites such as the face, future studies are needed to understand the relative influence of coverage and cost as well as clinician and patient preferences to ensure optimal TCI access. To the Editor: The American Academy of Dermatology's guidelines recommend topical calcineurin inhibitors (TCIs) for acute and maintenance treatment of atopic dermatitis (AD).1Eichenfield L.F. Tom W.L. Berger T.G. et al.Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies.J Am Acad Dermatol. 2014; 71: 116-132https://doi.org/10.1016/j.jaad.2014.03.023Abstract Full Text Full Text PDF PubMed Scopus (744) Google Scholar TCIs have minimal risk of skin atrophy and discoloration, can reduce the need for topical corticosteroids (TCSs), and have an excellent safety profile, with no evidence of clinically meaningful increase in malignancy rates relative to malignancy rates in the general population in long-term follow-up studies.1Eichenfield L.F. Tom W.L. Berger T.G. et al.Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies.J Am Acad Dermatol. 2014; 71: 116-132https://doi.org/10.1016/j.jaad.2014.03.023Abstract Full Text Full Text PDF PubMed Scopus (744) Google Scholar,2Lam M. Zhu J.W. Tadrous M. Drucker A.M. Association between topical calcineurin inhibitor use and risk of cancer, including lymphoma, keratinocyte carcinoma, and melanoma: a systematic review and meta-analysis.JAMA Dermatol. 2021; 157: 549-558https://doi.org/10.1001/jamadermatol.2021.0345Crossref PubMed Scopus (13) Google Scholar Given these benefits, one would expect TCIs to be preferable to TCSs, particularly in sensitive areas. However, although they are now generic, TCIs can be more expensive and difficult to obtain than TCSs. In addition, little research has been done on the use patterns of TCIs in patients with AD. Therefore, we sought to evaluate the use of TCIs compared with the use of TCSs for AD in clinically sensitive areas. We conducted a retrospective analysis using the Pediatric Eczema Elective Registry's data set, a previously described longitudinal cohort of US individuals with mild-to-moderate AD.3Margolis J.S. Abuabara K. Bilker W. Hoffstad O. Margolis D.J. Persistence of mild to moderate atopic dermatitis.JAMA Dermatol. 2014; 150: 593-600https://doi.org/10.1001/jamadermatol.2013.10271Crossref PubMed Scopus (186) Google Scholar The individuals were required to use pimecrolimus for ≥6 weeks out of the 6 months preceding enrollment. At 6-month intervals for up to 10 years, the individuals reported the presence and location of the disease; use of Elidel cream, Protopic ointment, and TCSs; and location of treatment application. The individuals were not required to continue pimecrolimus after enrollment. In the study, no medications were provided to the study subjects; the sponsor had no role in treatment decisions. We evaluated surveys reporting a concurrent acute-to-chronic AD rash and medication use at particular sites over time. Proportional odds logistic regression models were used to evaluate the association between year of follow-up and likelihood of using TCIs. The models were adjusted for ethnicity, sex, and income; the outcome variable was the difference between TCI and steroid use, arranged on an ordinal scale. Implementation was done using the “polr” function (package MASS 7.3-54) in R 3.6.1. Eight thousand fifteen subjects completed 82,591 surveys, representing >40,000 person-years of follow-up. During year 1, 53% of the surveys reported a rash on the face; this decreased to 31% by year 10. Similar trends were observed for other rash locations. The likelihood of using TCIs decreased over time (Figs 1 and 2). These trends persisted after adjusting for race, income, and sex (rash on the face: odds ratio [95% CI], 0.880 [0.874-0.886], P < .001; upper extremities: odds ratio [95% CI], 0.895 [0.889-0.901], P < .001; and lower extremities: odds ratio [95% CI], 0.897 [0.891-0.903], P < .001). Despite the potential clinical value of TCIs for AD, particularly on sites such as the face, TCI use decreased over time among the Pediatric Eczema Elective Registry individuals. Shift from TCIs to TCSs was observed across both the sensitive sites and other locations, suggesting that rash location did not influence treatment choice. This shift persisted after adjusting for sociodemographic factors. Difficulties with respect to coverage and cost, TCI tolerability, or patient and clinician preferences may have been responsible for these observed trends. The Pediatric Eczema Elective Registry study only provides information on patient practices and does not allow us to differentiate between these possibilities. Although our findings suggest that TCIs are underused among individuals with AD, particularly for sensitive sites such as the face, future studies are needed to understand the relative influence of coverage and cost as well as clinician and patient preferences to ensure optimal TCI access. Dr Margolis is a consultant for Pfizer, Leo, and Sanofi with respect to studies of atopic dermatitis and serves on the advisory board for the National Eczema Association. Dr Barbieri and Author Berna have no conflicts of interest to declare.