Effect of Methotrexate on Inflammatory Response in Adult Atopic Dermatitis Patients

Evaluation of the Effect of Methotrexate on Cytokines and Chemokines Involved in the Inflammatory Response in Adult Patients With Atopic Dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with pruritus. Methotrexate can be used to treat refractory disease to conventional therapy.

It will be conducted a single arm trial with twelve adult patients with moderate to severe AD on methotrexate for 24 weeks.

Investigators intend to evaluate the effect methotrexate on cytokines and chemokines involved in the inflammatory response, on IgE levels, on pruritus, and on EASI and SCORAD severity scores.

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Methotrexate

Detailed Description

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with pruritus. Methotrexate (MTX) can be used to treat refractory disease to conventional therapy, but there are few studies showing its effect on the profile of cytokines involved in the inflammatory response.

Objectives: To assess the effect of MTX on the cytokines involved in the inflammatory response of adult AD patients treated with methotrexate for 24 weeks. As specific objectives, investigators intend to assess the evolution of serum IgE levels, the EASI (Eczema Area and Severity Index) and SCORAD (Scoring Atopic Dermatitis) severity scores and pruritus in them.

Methods: It will be conducted an open, prospective study with twelve adult patients with moderate to severe AD on MTX for 24 weeks. Each participant is expected to attend 7 visits during 6 months of follow-up. In clinical healthy and injured skin, two assessments will be performed: 1) mRNA expression of IL-4, IL-10, IL-17A, IL-22, IL-31, oncostatin M receptor (OSMR), alpha subunit IL-31 (IL-31RA) receptor, TNF-α, IFN-γ, TSLP, TARC and MDC by Real Time-PCR at the initial week and week 24; 2) expression of IL-31, IL-31RA, OSMR, TSLP and Ki67 by immunohistochemistry at the initial week and week 24.

Skin samples from non-atopic subjects will be utilized as controls for the assays, paired by gender and age.

Additional analysis of serum levels of IgE (nephelometric method) at the initial week and week 24 of the study will be performed.

AD severity scores (EASI and SCORAD) will be tested and pruritus will be analyzed by a visual analog scale at the initial, week 12 and week 24.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • SP
    • São Paulo, SP, Brazil, 05403900
      • Hospital das Clínicas of the University of São Paulo Medical School, Department of Dermatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• AD (Hanifin and Rajka criteria) moderate to severe (EASI ≥ 7.1 and SCORAD ≥ 25);
• Age ≥ 18 years;
• Women without the potential to become pregnant or using an effective method of contraception and with a negative pregnancy blood test;
• Men without a desire of pregnancy and who use condom in sexual intercourse.

Exclusion Criteria:

• Hepatic and / or renal insufficiency;
• Anemia, thrombocytopenia and / or leukopenia;
• Use of concomitant hepatotoxic drug;
• Active infection;
• Allergy to MTX;
• Excessive alcohol intake;
• Difficulty to understand how to take methotrexate;
• HIV infection or other immunosuppression condition;
• Therapy with UVA or UVB, corticoid, cyclosporine, immunobiological, azathioprine within 12 weeks prior to introduction of methotrexate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methotrexate	Drug: Methotrexate; oral, 15 mg per week, 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline of cytokines and chemokines expression at 24 weeks	mRNA expression of IL-4, IL-6, IL-10, IL-31, TSLP, INF-gamma, TNF-alpha, TARC and MDC by Real Time-PCR. Immunohistochemistry with antibodies against IL-31, IL-31RA, OSMR, TSLP and Ki67	week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline of IgE level at 24 weeks	Nephelometric method	week 24
Change from baseline of Pruritus at 12 weeks	Visual analogue scale (VAS). The VAS was used as a 10-cm long horizontal line with a starting point as "no itch" (0 points) and ending with "worst imaginable itch".	week 12
Change from baseline of Pruritus at 24 weeks	Visual analogue scale (VAS). The VAS was used as a 10-cm long horizontal line with a starting point as "no itch" (0 points) and ending with "worst imaginable itch".	week 24
Change from baseline of SCORAD severity score at 12 weeks	The SCORAD (Scoring atopic dermatitis) is a severity score used for atopic dermatitis. To measure the extent of AD, the rule of nines is applied on a front/back drawing of the patient's inflammatory lesions. The extent can be graded from 0 to 100. The intensity part of the SCORAD consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness. Each item can be graded on a scale from 0 to 3. The subjective items include daily pruritus and sleeplessness. The SCORAD Index formula is: A/5 + 7B/2 + C. In this formula, A is defined as the extent (0-100), B is defined as the intensity (0-18) and C is defined as the subjective symptoms (0-20). The minimal score of SCORAD is 0 and the maximal score is 103 (most severe).	week 12
Change from baseline of SCORAD severity score at 24 weeks	The SCORAD (Scoring atopic dermatitis) is a severity score used for atopic dermatitis. To measure the extent of AD, the rule of nines is applied on a front/back drawing of the patient's inflammatory lesions. The extent can be graded from 0 to 100. The intensity part of the SCORAD consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness. Each item can be graded on a scale from 0 to 3. The subjective items include daily pruritus and sleeplessness. The SCORAD Index formula is: A/5 + 7B/2 + C. In this formula, A is defined as the extent (0-100), B is defined as the intensity (0-18) and C is defined as the subjective symptoms (0-20). The minimal score of SCORAD is 0 and the maximal score is 103 (most severe).	week 24
Change from baseline of EASI severity score at 12 weeks	Eczema Area and Severity Index (EASI) is a tool for the measurement of severity of atopic dermatitis. It ranges from 0 (no eczema) to 72 (most severe). EASI is one of the core outcome instruments recommended to be included in all clinical trials on atopic dermatitis.	week 12
Change from baseline of EASI severity score at 24 weeks	Eczema Area and Severity Index (EASI) is a tool for the measurement of severity of atopic dermatitis. It ranges from 0 (no eczema) to 72 (most severe).	week 24

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Collaborators: FUNADERSP (Foundation for Research Support of the State of São Paulo)

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2017
• Primary Completion (Actual): July 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: July 30, 2017
• First Submitted That Met QC Criteria: October 25, 2017
• First Posted (Actual): October 31, 2017

Study Record Updates

• Last Update Posted (Actual): December 13, 2019
• Last Update Submitted That Met QC Criteria: December 11, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: atopic dermatitis; methotrexate; pruritus; inflamation; IL-31
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: 13.368

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No