Tacrolimus Versus Hydrocortisone in Atopic Dermatitis

A Comparative Clinical Trial to Evaluate the Efficacy and Safety of Tacrolimus Versus Hydrocortisone in Treatment of Children With Atopic Dermatitis

Atopic dermatitis (AD) is a very common inflammatory, genetic skin disorder that occurs more frequently in children. Its exact etiology is not known but it is characterized by pruritic skin reactions with elevation in the levels of inflammatory markers. Corticosteroids are the first line and the mainstay therapy in management of atopic dermatitis but have many local and systemic adverse effects. The study aims to evaluate the efficacy and safety of topical tacrolimus ointment in comparison to topical hydrocortisone cream in management of children diagnosed with atopic dermatitis.

Study Overview

• Status: Completed
• Conditions: Dermatitis; Atopic
• Intervention / Treatment: Drug: Tacrolimus; Drug: Hydrocortisone

Detailed Description

Atopic dermatitis is a common pruritic inflammatory skin disorder. The prevalence of atopic dermatitis increased in the last three decades by two or three folds worldwide. In the developed countries, atopic dermatitis is estimated to affect 15% to 30% of children and 2% to 10% of adults. This type of dermatitis is usually associated with family history of other atopic disorders such as allergic rhinitis or asthma.

The clinical presentation of Atopic dermatitis differs depending on the age of the patient, it usually begins in infancy with erythematous, papular skin rash that may first appear on the cheeks and chin. In childhood, the skin appears dry, flaky, rough, cracked, and may bleed because of scratching, in adults the lesions are more diffuse with underlying erythema.

This condition is characterized by acute phase where the skin has red scaly patches and chronic phase in which the skin thickens.

Atopic dermatitis is a complex genetic disease where the exact etiology is not entirely known, but it is most probably due to interaction between environmental and genetic factors. The two major groups of involved genes are the genes encoding for epidermal and epithelial structural proteins and the genes regulating the production of cytokines for the immune response.

In atopic dermatitis patients, imbalance occurs between T helper-1 (TH1) and T helper-2 (TH2) immune responses, increased TH2 activity causes the release of interleukin (IL)-3, IL-4, IL-5, IL-10, and IL-13 which results in blood eosinophilia, increased total serum immunoglobulin (Ig) E, and increased growth and development of mast cells.

Atopic dermatitis patients are more likely to develop different skin infections as compared to healthy individuals, including: staphylococcal secondary bacterial infections and herpes simplex viral infection.

Topical corticosteroids (TCS) are the mainstay for management of atopic dermatitis to which other treatments are compared, they act by many pathways to reduce inflammation. Although TCS are effective treatment, they have both local adverse effects as skin thinning, striae, perioral dermatitis, acne, rosacea, telangiectasias, purpura and focal hypertrichosis. Moreover, systemic absorption can lead to systemic effects such as hypothalamic-pituitary-adrenal (HPA) axis suppression, infections, hyperglycemia, cataracts, glaucoma, and growth retardation (in children).

All these side effects are more likely to occur with prolonged use and so seeking for other treatment options is crucial.

Topical calcineurin inhibitors (TCI) as tacrolimus and pimecrolimus are immunosuppressives that help to control the acute flares and decrease the severity of the new flares by acting as immunomodulators. They inhibit the calcineurin so inhibit the T-cell proliferation that produces many inflammatory cytokines such as IL-2, IL-3, IL-4, IL-17, tumor necrosis factor (TNF). TCI is more selective as compared to TCS with less adverse effects so it is considered as an acceptable alternative to TCS.

Tacrolimus 0.03% ointment is approved for moderate to severe atopic dermatitis for ages 2 years and older, with the 0.1% ointment limited to ages 16 years and older; pimecrolimus 1% cream is approved for mild-to-moderate atopic dermatitis for ages 2 years and older. There is limited data comparing TCS with tacrolimus or pimecrolimus.

The FDA has a black box warning for both tacrolimus ointment and pimecrolimus cream about their potential local skin carcinogenesis as seen in animal studies. However, till now there is no causal relationship has been proven between use of a TCI and the development of lymphoma or non-melanoma skin cancer.

This study aims to assess the efficacy and safety of topical tacrolimus ointment in comparison to topical hydrocortisone cream in children diagnosed with atopic dermatitis. The primary outcome is to evaluate the effect of topical tacrolimus ointment as compared to topical hydrocortisone cream by estimation of the serum level of inflammatory cytokines and the effect on the dermatitis severity scale. The secondary outcome is to evaluate the tacrolimus safety as compared to hydrocortisone through the assessment of treatment related toxicities.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Amal A. Mohamed, Prof.; Phone Number: +201224847367; Email: amalahmedhcp@yahoo.com
• Study Contact Backup: Name: Amal A. Elkholy; Phone Number: +201060355448; Email: amalanas9@gmail.com

Study Locations

• Egypt
  • Cairo, Egypt, 123456
    • Dermatology Clinic of National Hepatology and Tropical Medicine Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 16 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female patients
• 2-16 years old
• diagnosed with Atopic Dermatitis according to Hanifin and Rajka criteria

Exclusion Criteria:

• patients with serious skin disorder other than Atopic Dermatitis
• patients taking systemic corticosteroids or anti-inflammatory medications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tacrolimus group; 100 patients treated by thin layer of 0.03% topical tacrolimus ointment on the affected areas twice daily for 4 months.	Drug: Tacrolimus; 0.03% topical tacrolimus ointment applied on the affected areas twice daily for 4 months.; Other Names: Tacrolimus (Tacrolimus 0.03%®) was manufactured by AL-Andalous company for pharmaceutical and chemical industries, Egypt.
Active Comparator: Hydrocortisone group; 100 patients treated by thin layer of 1% hydrocortisone cream on the affected areas twice daily for 4 months.	Drug: Hydrocortisone; 1% hydrocortisone cream applied on the affected areas twice daily for 4 months.; Other Names: Hydrocortisone (Micort 1%®) was manufactured by Cid company for pharmaceutical and chemical industries, Egypt.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
evaluate the effect of topical tacrolimus ointment as compared to topical hydrocortisone cream on the serum level of different inflammatory cytokines using enzyme linked immunosorbent assay technique (ELISA)	estimation of the serum level of inflammatory cytokines (biochemical evaluation of IL-10 (pg/ml), IL-17 (pg/ml), IL-23 (pg/ml) using enzyme linked immunosorbent assay technique (ELISA)	4 months
severity assessment	Estimation of the effect on the dermatitis severity scale using the modified Eczema Area and Severity Index (mEASI) score. It is a tool used to evaluate the severity of eczema based on body surface area affected by lesions, morphology of lesions (erythema, papules, excoriation, and lichenification), severity of lesions (0-3), and pruritus. The scores range from 0 to 72 for the main symptoms of AD and from 0 to 18 for pruritus, giving a maximum possible score of 0 (no involvement) to 90 (maximum involvement), (0-0.9 clear, 1-8.9 mild, 9.0-29.9 moderate, 30.0-90 severe).	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
evaluate the tacrolimus safety	assessment of treatment related toxicities; assessment of the incidence rate of burning	4 months
evaluation of tacrolimus safety	assessment of other tacrolimus related toxicity; the incidence rate of stinging sensation	4 months
evaluation of safety of tacrolimus	assessment of the degree of erythema using Eczema Area and Severity Index (EASI). The EASI is a composite score comprising ratings of the severity of erythema, oedema/induration/papulation, excoriations and lichenification; each on a scale from 0 to 3.	4 months
evaluate the hydrocortisone safety	assessment of the incidence rate of skin atrophy and skin infection.	4 months

Collaborators and Investigators

• Sponsor: Ain Shams University
• Collaborators: National Hepatology & Tropical Medicine Research Institute
• Investigators: Principal Investigator: Amal A. Mohamed, Department of Biochemistry, National Hepatology and Tropical Medicine Research institute

Publications and helpful links

General Publications

• Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M. The eczema area and severity index (EASI): assessment of reliability in atopic dermatitis. EASI Evaluator Group. Exp Dermatol. 2001 Feb;10(1):11-8. doi: 10.1034/j.1600-0625.2001.100102.x.
• Alaiti S, Kang S, Fiedler VC, Ellis CN, Spurlin DV, Fader D, Ulyanov G, Gadgil SD, Tanase A, Lawrence I, Scotellaro P, Raye K, Bekersky I. Tacrolimus (FK506) ointment for atopic dermatitis: a phase I study in adults and children. J Am Acad Dermatol. 1998 Jan;38(1):69-76. doi: 10.1016/s0190-9622(98)70541-9.
• Reitamo S, Rustin M, Ruzicka T, Cambazard F, Kalimo K, Friedmann PS, Schoepf E, Lahfa M, Diepgen TL, Judodihardjo H, Wollenberg A, Berth-Jones J, Bieber T; European Tacrolimus Ointment Study Group. Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone butyrate ointment in adult patients with atopic dermatitis. J Allergy Clin Immunol. 2002 Mar;109(3):547-55. doi: 10.1067/mai.2002.121832.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2022
• Primary Completion (Actual): November 20, 2022
• Study Completion (Actual): April 30, 2023

Study Registration Dates

• First Submitted: January 16, 2022
• First Submitted That Met QC Criteria: April 5, 2022
• First Posted (Actual): April 12, 2022

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 21, 2023
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: children; Tacrolimus; Hydrocortisone; Atopic; Dermatits
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Dermatitis, Atopic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate
• Other Study ID Numbers: Tacrolimus vs Hydrocortisone

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No