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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Flexural Psoriasis (Also Known as Inverse or Intertriginous Psoriasis) and Genital Psoriasis
• Intervention / Treatment: Drug: Methotrexate; Drug: Roflumilast 500 Mcg Oral Tablet

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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".

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Weekly Methotrexate (0.2-0.4 mg/kg); 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; 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.; Other Names: MTX
Experimental: Oral Roflumilast 500 mcg daily; 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; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global Skin Clearance (PASI Responses)	The proportion of patients achieving clinically significant reductions in disease severity as measured by the Psoriasis Area and Severity Index (PASI), specifically the PASI 75, PASI 90, and PASI 100 benchmarks (representing ≥75%, ≥90%, and 100% improvement from baseline, respectively)	Week 16
Quality of Life Improvement (DLQI 0/1)	The proportion of patients achieving a Dermatology Life Quality Index (DLQI) score of 0 or 1, signifying that the skin condition has no impact at all on the patient's overall quality of life.	week 16
Itch Relief (Itch-NRS)	The proportion of patients achieving a clinically meaningful ≥4-point reduction from baseline in the Itch Numeric Rating Scale (Itch-NRS) or reaching an absolute score of 0 or 1 (no itch or minimal itch)	week 16
Safety and Tolerability (Adverse Events)	The incidence, nature, and severity of treatment-related adverse events (AEs) and serious adverse events (SAEs) documented in both treatment arms. This includes monitoring for dropouts specifically due to drug-related side effects.	Throughout the 16-week treatment period and during the follow-up period (at least 3 months)
Body Surface Area (BSA) Reduction	The proportion of patients achieving an absolute Body Surface Area (BSA) involvement of ≤1% or the mean percentage change in BSA from baseline to the end of the study.	week 16

Collaborators and Investigators

• Sponsor: Eman Raafat Said

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: April 14, 2026
• First Submitted That Met QC Criteria: April 14, 2026
• First Posted (Actual): April 22, 2026

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Roflumilast, Methotrexate, Genital Psoriasis, Flexural Psoriasis, Inverse Psoriasis, PDE-4 Inhibitor, Quality of Life, Pruritus
• Additional Relevant MeSH Terms: Skin Manifestations; Skin Diseases; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Signs and Symptoms; Pruritus; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Dosage Forms; Pterins; Pteridines; Aminopterin; Methotrexate; Tablets; Roflumilast
• Other Study ID Numbers: MS-506-2024

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