EFFICACY OF ROFLUMILAST IN THE TREATMENT OF FLEXURAL AND/OR GENITAL PSORIASIS: A RANDOMIZED CONTROLLED TRIAL.

NCT07543640 | Not Yet Recruiting Phase 2

• 1 other identifier: MS-506-2024
• Study Type: interventional
• Target: 56
• Locations: 0 countries
• Sites: N/A

Brief Summary

Psoriasis affecting sensitive anatomical regions, such as the skin folds (flexural or inverse psoriasis) and genitalia, presents unique therapeutic challenges. These manifestations often result in a disproportionately high burden of disease, causing significant physical discomfort and a profound negative impact on a patient's quality of life and sexual health. While topical creams are the standard first-line treatment, many patients have "topically resistant" disease that requires a systemic (oral) approach. This 16-week randomized controlled trial is the first to directly compare two oral medications for these specific sites: roflumilast (a daily 500 mcg pill) and methotrexate (a standard weekly dose). The study's primary objective is to evaluate which treatment is more effective at clearing psoriatic lesions in the skin folds and genital area, and how each drug improves the patient's overall quality of life and symptoms like pruritus (itching). Participants are randomly assigned to one of the two treatment groups and are monitored monthly to assess skin clearance, symptom relief, and safety/tolerability. The goal of this research is to provide patients and healthcare providers with evidence-based data on a convenient, oral treatment option that does not require intensive laboratory monitoring.

Conditions

Flexural Psoriasis (Also Known as Inverse or Intertriginous Psoriasis) and Genital Psoriasis

Keywords

Roflumilast, Methotrexate, Genital Psoriasis, Flexural Psoriasis, Inverse Psoriasis, PDE-4 Inhibitor, Quality of Life, Pruritus

Outcome Measures

Primary Outcomes (1)

• Clinical Success at flexural (I-IGA 0/1) and/or genital (sPGA-G 0/1) psoriasis

  The proportion of patients achieving a score of 0 (clear) or 1 (almost clear) with at least a 2-point improvement from baseline at the specific sensitive sites. This is assessed using the Investigator's Global Assessment for Flexural Psoriasis (I-IGA) for skin folds and the static Physician's Global Assessment of Genitalia (sPGA-G) for genital involvement.

  week 16

Secondary Outcomes (5)

• Global Skin Clearance (PASI Responses)

  Week 16

• Quality of Life Improvement (DLQI 0/1)

  week 16

• Itch Relief (Itch-NRS)

  week 16

• Safety and Tolerability (Adverse Events)

  Throughout the 16-week treatment period and during the follow-up period (at least 3 months)

• Body Surface Area (BSA) Reduction

  week 16

Study Arms (2)

Weekly Methotrexate (0.2-0.4 mg/kg)

ACTIVE COMPARATOR

This arm receives methotrexate at a dose of 0.2-0.4 mg/kg once weekly for 16 weeks. As methotrexate is a well-established standard systemic therapy for psoriasis, it serves as the active control to which the experimental drug is being compared

Drug: Methotrexate

Oral Roflumilast 500 mcg daily

EXPERIMENTAL

This arm receives oral roflumilast at a fixed dose of 500 mcg once per day for 16 weeks. Since systemic roflumilast is currently used off-label for psoriasis and is the novel intervention being investigated in this study, it is classified as the experimental arm.

Drug: Roflumilast 500 Mcg Oral Tablet

Interventions

Methotrexate DRUG

Participants in this arm receive methotrexate at a weight-based dosage of 0.2-0.4 mg/kg administered once weekly for 16 weeks. Distinguishing Details: Methotrexate serves as the established active comparator and is a cornerstone of traditional systemic psoriasis therapy. It distinguishes itself from the experimental arm through its mechanism as a non-biologic immunosuppressant, and its requirement for comprehensive baseline and periodic laboratory monitoring of liver function, kidney function, and complete blood counts to manage potential toxicities. In this study, it is used to provide a benchmark for efficacy in clearing sensitive "special sites" like skin folds and genitalia.

Also known as: MTX

Weekly Methotrexate (0.2-0.4 mg/kg)

Roflumilast 500 Mcg Oral Tablet DRUG

Participants in this arm receive oral roflumilast at a fixed dose of 500 mcg administered once daily for a total of 16 weeks. Distinguishing Details: While roflumilast is a selective and potent phosphodiesterase-4 (PDE-4) inhibitor, this study evaluates its off-label systemic use specifically for flexural and/or genital psoriasis that has proven resistant to topical therapy. Unlike its counterpart apremilast, the protocol for this study involves a fixed dose without an initial titration phase. Furthermore, as a systemic small molecule, it distinguishes itself from traditional therapies by its lack of requirement for intensive, ongoing laboratory blood monitoring

Oral Roflumilast 500 mcg daily

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥ 18 years old.
• Patients of both genders.
• Patients with flexural and/or genital psoriasis that has been resistant to topical treatment, "No clearance or near clearance of lesions despite being compliant to treatment for 4 to 6 weeks".

You may not qualify if:

• Major systemic illness (cardiac, respiratory, renal, hepatic and gastrointestinal system).
• Severe anemia, leucopenia or thrombocytopenia.
• Pregnant and breastfeeding females.
• Hypersensitivity /intolerance to Roflumilast or methotrexate.
• Intake of systemic therapy for psoriasis within the last 3 Months.
• Patients receiving any relevant topical treatment for at least 2 weeks before initiation of our study.
• Erythrodermic, pustular psoriasis or psoriatic arthritis.
• Patients with autoimmune diseases e.g., SLE.
• Patients with solid or hematological malignancies e.g., breast cancer, leukemia, etc.
• Patients on biological therapy within the last 6 months prior to recruitment.

Sponsors & Collaborators

• Eman Raafat Said: lead

MeSH Terms

Conditions

Pruritus

Interventions

Methotrexate; Roflumilast; Tablets

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: April 14, 2026
• First Posted: April 22, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: April 22, 2026

Record last verified: 2026-04