Dupilumab and House Dust Mite Immunotherapy in Patients With Atopic Dermatitis (DuHDM)

Severe atopic dermatitis (AD) is a complex disease requiring systemic treatment. This study aimed to assess the effectiveness of combined therapy consisting of dupilumab and sublingual dust mite allergen immunotherapy (SLIT-HDM) in patients with severe AD and HDM allergies.

Methods: Patients diagnosed with severe AD were included in a randomized, placebo-controlled, double-blind 12-month trial; they received SLIT to HDM and/or dupilumab for 12 months and were compared to patients on cyclosporine. EASI, %BSA, and IsGA changes were analyzed in the different treatment arms from the beginning to the end of the 12th month. The secondary outcomes were the proportion of patients who achieved IsGA success and reduced medication scores.

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Biological: tablets Acarizax; Biological: dupilumab; Drug: cyclosporine

Detailed Description

Study design This randomized, 12-month trial has performed in the Clinical Outpatient Allergy Department and six other outpatient cities. All included patients has received SLIT to HDM and/or dupilumab for 12 months and were compared to patients on cyclosporine.

Patients Patients were eligible if they met the following criteria: were diagnosed with AD a minimum of one year before the study (documented one year of therapy for AD); were between 18 and 45 years of age; had severe AD with an Eczema Area and Severity Index (EASI) >20 points, a %BSA (body surface area) >10 points, an IsGA (Investigator Global Assessment) = 4 points, a positive skin prick test (SPT) and a positive result for specific immunoglobulin E (sIgE) to extracts of D. pteronyssinus and D. farinae and to Der p 1; had negative results for SPT and sIgE to other inhalant allergens; and had no symptoms of allergic asthma and/or allergic rhinitis. The diagnosis of severe AD was based on the guidelines of the Polish Dermatological Society with more restrictive cut-off points on the EASI, %BSA, and IsGA scales, as presented in the inclusion criteria, to limit the study group to the most advanced forms of AD.14

The exclusion criteria included the following: other active dermatoses, systemic immunosuppressant treatment up to 7 months before the study, other chronic diseases, contraindications to sublingual immunotherapy or sarilumab, and lack of written consent. The dermatologist assessed signs of AD at each study visit.

Treatment The patients have received SLIT-HDM (ACARIZAX, ALk Abello, Denmark) with 12 SQ-HDMs of a standardized allergen extract of the house dust mites Dermatophagoides pteronyssinus and Dermatophagoides farinae (50/50%). The Acarizax tablets were removed from the blister unit immediately after opening the blister and placed under the tongue, where they were dissolved. Swallowing was avoided for approximately 2 minutes. Food and beverages were not ingested for 5 minutes after intake of the tablet. The daily dose was one tablet every day for 12 months. Dupilumab treatment was administered according to established recommendations. Briefly, the patient received a single initial dose of 600 mg of dupilumab followed by subsequent doses of 300 mg every 2 weeks.

All patients used emollients. During therapy, patients with clinical signs of bacterially infected skin were allowed to receive treatment with topical mupirocin or/and a 7-day course of amoxicillin or/and prednisolone (0.5 mg/kg) for seven days for any occurrence of skin exacerbation, including superinfection. In the control group, cyclosporine was administered at 3.5 mg/kg at the start of therapy, with the possibility of modifying the dose according to symptoms after a minimum of 6 months of therapy. Further treatment was administered for a minimum of another six months (12 months in total). Treatment was discontinued if adverse effects occurred.

In all groups, oral antihistamines such as desloratadine and topical medications were added depending on the individual disease. If there was clinical worsening of AD (reported significant severity of itching, the appearance of erythroderma, and new skin lesions of a large area), the patient also received oral glucocorticosteroids at a dose of 10 mg of encortolon per 7 days.

Symptomatic treatment was assessed via the following medication scores: one point for daily use of desloratadine, mometasone furoate cream, or mupirocin ointment, 7 points for every course of amoxicillin and 10 points for the course of encortolon. The patients were required to record symptomatic drug use on the diary card

The statistical analysis was performed using Statistica version 8.12 (SoftPol, Cracow, Poland). Nonparametric tests were used because the data were not normally distributed. The Wilcoxon test was used to analyse differences between the groups. ANOVA was used to compare the scale scores. Differences were considered significant at p < 0.05.

• Study Type: Interventional
• Enrollment (Actual): 132
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Poland
  • Zabrze, Poland
    • SUM

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• diagnosed with AD a minimum of one year before the study (documented one year of therapy for AD)
• between 18 and 45 years of age
• severe AD with an Eczema Area and Severity Index (EASI) >20 points, a %BSA (body surface area) >10 points, an IsGA (Investigator Global Assessment) = 4 points, a positive skin prick test (SPT)
• a positive result for specific immunoglobulin E (sIgE) to extracts of D. pteronyssinus and D. farinae and to Der p 1;
• negative results for SPT and sIgE to other inhalant allergens;
• no symptoms of allergic asthma and/or allergic rhinitis

Exclusion Criteria:

• other active dermatoses, systemic immunosuppressant treatment up to 7 months before the study, other chronic diseases,
• contraindications to sublingual immunotherapy or dupilumab,
• lack of written consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: SLIT HDM; Patients received sublingual allergen immunotherapy (Acarizax), adding to symptomatic therapy for atopic dermatitis (according to recommendations).	Biological: tablets Acarizax; sublingual immunotherapy to house dust mites
Active Comparator: biologic; Patients received dupilumab, added to symptomatic therapy for atopic dermatitis (according to recommendations.)	Biological: dupilumab; dupilumab - biologic therapy for atopic dermatitis
Active Comparator: Combi therapy; Patients received sublingual allergen immunotherapy (Acarizax) and dupilumab, added to symptomatic therapy for atopic dermatitis (according to recommendations).	Biological: tablets Acarizax; sublingual immunotherapy to house dust mites; Biological: dupilumab; dupilumab - biologic therapy for atopic dermatitis
Placebo Comparator: cyclosporine; Patients received cyclosporine added to symptomatic therapy for atopic dermatitis (according to recommendations).	Drug: cyclosporine; cyclosporine used in atopic dermatitis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in EASI (the Eczema Area and Severity Index) scale	objective improvement of skin lesions in the course of atopic dermatitis based on assessment using standardized questionnaire tests EASI. The EASI assessed disease extent on a scale of 0 to 6 in 4 defined body regions plus an assessment of erythema, infiltration, and/or population; excoriation; and lichenification, each on a scale of 0 to 3. A formula was then used to calculate the total score for each of the 4 regions, which were then added together. Interpretation of the EASI result: 0 = no change, 0.1-1.0 = almost no change, 1.1-7.0 = mild in intensity, 7.1-21.0 = moderate intensity, 21.1-50.0 = high intensity, 50.1-72.0 = very severe (points)	12 months
Changes in BSA% (Body Surface Area) scale	Ii atopic dermatitis, %BSA was categorised according to severity bands: clear (0%), mild (> 0 to < 16%), moderate (16 to < 40%), and severe (40-100%) (percentage)	12 months
Changes in IsGA (investigator global assessment) scale	The IsGA is a doctor-assessed outcome that evaluates overall AD severity on a 5-point scale ranging from clear (0) to severe (4) or very severe (5).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Significant reduction in IsGA scale	the proportion of patients who achieved IsGA success (defined as a ≥2-grade improvement in IsGA from baseline	12 months
changes in DLQI (Dermatology Life Quality Index ) questionnaire	DLQI is a ten-question questionnaire used to measure the impact of skin disease on the quality of life of an affected person. It is de-signed for people aged 16 years and above.	12 months
exacerbations of atopic dermatitis	number of exacerbations of atopic dermatitis per year of observation. Definition:in terms of the need to use systemic steroids.	12 months
changes in serum concentration of IgG4 against D. pteronyssinus	assessment of allergen-specific IgG4 concentration in blood serum after 6 and 12 months of treatment in arms with the addition of sublingual immunotherapy SLIT-HDM (AU/L)	12 months
changes in serum concentration of IgE against D. pteronyssinus	assessment of allergen-specific IgE concentration in blood serum after 6 and 12 months of treatment in arms with the addition of sublingual immunotherapy SLIT-HDM (kU/L)	12 months

Collaborators and Investigators

• Sponsor: Medical University of Silesia
• Investigators: Principal Investigator: Andrzej Bozek, Prof, Medical University of Silesia

Publications and helpful links

General Publications

• Bogacz-Piaseczynska A, Bozek A. The Effectiveness of Allergen Immunotherapy in Adult Patients with Atopic Dermatitis Allergic to House Dust Mites. Medicina (Kaunas). 2022 Dec 21;59(1):15. doi: 10.3390/medicina59010015.

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2023
• Primary Completion (Actual): March 12, 2024
• Study Completion (Actual): April 10, 2024

Study Registration Dates

• First Submitted: June 5, 2024
• First Submitted That Met QC Criteria: July 12, 2024
• First Posted (Actual): July 19, 2024

Study Record Updates

• Last Update Posted (Actual): July 19, 2024
• Last Update Submitted That Met QC Criteria: July 12, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: atopic dermatitis; biologics; allergen immunotherapy
• 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; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: KNW-1-131/N/9/K

Drug and device information, study documents

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