Effects of topical corticosteroid versus tacrolimus on insulin sensitivity and bone homeostasis in adults with atopic dermatitis-A randomized controlled study

Lise Gether^{1

2

3}, Heidi Storgaard^{1

4}, Sanja Kezic⁵, Ivone Jakasa⁶, Bolette Hartmann^{7

8}, Kirsa Skov-Jeppesen^{7

8}, Jens J Holst^{7

8}, Anders J Pedersen³, Julie Forman⁹, Gerrit van Hall^{7

10}, Ole E Sørensen³, Lone Skov^{2

11}, Mads A Røpke^{3

12}, Filip K Knop^{1

8

11}, Jacob Pontoppidan Thyssen^{11

13}

Affiliations

¹ Center for Clinical Metabolic Research, Herlev-Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
² Department of Dermatology and Allergy, Copenhagen Research Group for Inflammatory Skin (CORGIS), Herlev-Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
³ LEO Pharma A/S, Ballerup, Denmark.
⁴ Steno Diabetes Center Copenhagen, Copenhagen, Denmark.
⁵ Department of Public and Occupational Health, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
⁶ Department of Chemistry and Biochemistry, Laboratory for Analytical Chemistry, Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia.
⁷ Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁸ Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁹ Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
¹⁰ Clinical Metabolomics Core Facility, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
¹¹ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
¹² Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
¹³ Department of Dermatology and Venereology, Bispebjerg-Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.

PMID: 36824052
DOI: 10.1111/all.15690

Randomized Controlled Trial

Effects of topical corticosteroid versus tacrolimus on insulin sensitivity and bone homeostasis in adults with atopic dermatitis-A randomized controlled study

Lise Gether et al. Allergy. 2023 Jul.

. 2023 Jul;78(7):1964-1979.

doi: 10.1111/all.15690. Epub 2023 Mar 21.

Authors

Affiliations

¹ Center for Clinical Metabolic Research, Herlev-Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
² Department of Dermatology and Allergy, Copenhagen Research Group for Inflammatory Skin (CORGIS), Herlev-Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
³ LEO Pharma A/S, Ballerup, Denmark.
⁴ Steno Diabetes Center Copenhagen, Copenhagen, Denmark.
⁵ Department of Public and Occupational Health, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
⁶ Department of Chemistry and Biochemistry, Laboratory for Analytical Chemistry, Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia.
⁷ Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁸ Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁹ Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
¹⁰ Clinical Metabolomics Core Facility, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
¹¹ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
¹² Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
¹³ Department of Dermatology and Venereology, Bispebjerg-Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.

PMID: 36824052
DOI: 10.1111/all.15690

Abstract

Introduction: Topical corticosteroids (TCS), used to treat atopic dermatitis (AD), have been associated with type 2 diabetes and osteoporosis in epidemiological studies, possibly explained by systemic absorption.

Objectives: We examined whether intensive daily whole-body TCS treatment over 2 weeks followed by twice weekly application for 4 weeks could elicit insulin resistance and increase bone resorption in adults with AD.

Methods: A randomized parallel-group double-blind double-dummy non-corticosteroid-based active comparator study design was completed in Copenhagen, Denmark. Thirty-six non-obese, non-diabetic adults with moderate-to-severe AD were randomized to whole-body treatment with betamethasone 17-valerate 0.1% plus a vehicle once daily or tacrolimus 0.1% twice daily after washout. Insulin sensitivity assessed by the hyperinsulinemic-euglycemic clamp combined with tracer infusions and biomarkers of bone formation (P1NP) and resorption (CTX) were evaluated at baseline, after 2 weeks of daily treatment and after further 4 weeks of twice-weekly maintenance treatment.

Results: AD severity improved with both treatments and systemic inflammation was reduced. After 2 weeks, we observed similar increase in peripheral insulin sensitivity with use of betamethasone (n = 18) and tacrolimus (n = 18). Bone resorption biomarker, CTX, was unchanged, while bone formation marker, P1NP, decreased after betamethasone treatment after both 2 and 6 weeks but remained unchanged in the tacrolimus arm.

Conclusions: Whole-body treatment with TCS leads to systemic exposure but appears not to compromise glucose metabolism during short-term use, which may be a result of reduced systemic inflammatory activity. The negative impact on bone formation could be regarded an adverse effect of TCS.

Trial registration: ClinicalTrials.gov NCT04114097.

Keywords: atopic dermatitis; calcineurin inhibitor; corticosteroid; osteoporosis; type 2 diabetes.

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References

REFERENCES

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Effects of topical corticosteroid versus tacrolimus on insulin sensitivity and bone homeostasis in adults with atopic dermatitis-A randomized controlled study

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Effects of topical corticosteroid versus tacrolimus on insulin sensitivity and bone homeostasis in adults with atopic dermatitis-A randomized controlled study

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