The Effectiveness of Hydroxychloroquine Versus Methotrexate in the Treatment of Lichen Planopilaris in Routine Clinical Care: a Patient Preference Trial (HEMLET)

Rationale Lichen planopilaris (LPP) is a prevalent form of cicatricial alopecia, predominantly affecting women and causing irreversible hair loss. Hydroxychloroquine (HCQ) and methotrexate (MTX) are the most frequently used systemics for treatment of LPP in daily practice. Due to the absence of well-established treatment guidelines, this study aims to evaluate the effectiveness of HCQ and MTX in routine clinical care.

Objective(s) To investigate the effectiveness of HCQ and MTX in the treatment of adults with lichen planopilaris in routine clinical care.

Study type Prospective, patient preference clinical trial with a duration up to 48 weeks in accordance with the routine clinical care guidelines.

Study population This study will include adults (≥18 years) diagnosed with LPP.

Methods Patients will choose between HCQ and MTX treatment as in routine clinical care, receiving follow-up in accordance with standard clinical practices. They will not be randomized. The primary endpoint is the measurement of the Lichen Planopilaris Activity Index (LPPAI) at the 6-months, providing a quantitative assessment of the disease's activity and response to the selected treatment. The Skindex-29 questionnaire will be conducted at each visit, allowing evaluation of the impact on patients' quality of life.

Study Overview

• Status: Recruiting
• Conditions: Cicatricial Alopecia; Lichen Planopilaris
• Intervention / Treatment: Drug: Hydroxychloroquine; Drug: Methotrexate

Detailed Description

Treatment of LPP remains a challenge due to limited evidence-based guidelines and a lack of randomized controlled trials, leading to the absence of standardized therapeutic protocols and outcome measures. Currently, the treatment goal for LPP primarily focuses on halting disease progression to minimize further hair loss and alleviate associated symptoms. Treatment options for LPP include topical/intralesional corticosteroids, and systemic therapies such as hydroxychloroquine (HCQ), methotrexate (MTX), and other immunosuppressive agents. However, the absence of daily practice studies makes it challenging to establish therapeutic recommendations.

This patient preferred trial aims to fill a crucial knowledge gap in LPP management. Existing evidence lacks comprehensive guidelines for treating LPP effectively, leaving current approaches largely empirical. Aligning with the urgent need for answers highlighted by the 'Nederlandse Vereniging voor Dermatologie en Venereologie Kennisagenda Dermatologie 2019': 'Q9 - Wat is de effectiviteit van systemische behandeling bij patiënten met cicatriciële alopeciëen?' (What is the most effective systemic treatment for cicatricial alopecias) (13) underscores the pressing concern regarding the effectiveness of systemic therapy in cicatricial alopecia. This study seeks to contribute novel insights to the field by comparing the effectiveness of the two most commonly used systemic treatments, HCQ and MTX in treating LPP. By comparing the effectiveness and safety profiles of these systemics, this study endeavours to provide valuable information that can guide evidence-based treatment decisions and enhance the overall understanding of LPP management.

Objective(s)

The main objective is to assess the effectiveness in routine clinical care of hydroxychloroquine (HCQ) and methotrexate (MTX) in the treatment of adults diagnosed with lichen planopilaris (LPP) by evaluating the impact on the Lichen Planopilaris Activity Index (LPPAI) after a 6-month treatment period.

Primary objective:

To investigate the difference in LPPAI between baseline and 24 weeks of treatment between the HCQ and MTX group

Secondary objectives:

2. To compare LPPAI between HCQ and MTX at 0, 12, 24, 36, and 48 weeks.

3. To compare the quality of life between HCQ and MTX at 0, 12, 24, 36, and 48 weeks.

4. To compare the side effects of HCQ and MTX.

5. To compare the proportion of patients who discontinued therapy due to sides effects in both groups.

Skindex-29

The Skindex-29 is a dermatology-specific questionnaire. It evaluates the effect of skin conditions on physical, psychological, and social aspects. It assesses the extent to which a skin condition has influenced quality of life over the past week. The 29 questions are divided into 3 domains: symptoms, emotions, and functioning. A higher score corresponds to a greater impact on quality of life.

Other disease- and treatment-related characteristics will be retrieved from the electronic patient records.

• Study Type: Observational
• Enrollment (Estimated): 56

Contacts and Locations

• Study Contact: Name: Mathias Willaert, MD; Phone Number: (010) 704 01 10; Email: HEMLET@erasmusmc.nl

Study Locations

• Netherlands
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015GD
      • Recruiting
      • Erasmus MC
      • Contact: Mathias Willaert, MD; Phone Number: (010) 704 01 10; Email: HEMLET@erasmusmc.nl
      • Sub-Investigator: Mathias Willaert, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

All adult (≥18 years) patients diagnosed with LPP. All patients will be recruited at the dermatology outpatient clinics in the Erasmus University Medical Center.

Description

Inclusion Criteria:

• Age of 18 years and older.
• Diagnosed with LPP.
• Willingness to provide informed consent for participation in the study.
• No contraindications or known allergies to HCQ or MTX.

Exclusion Criteria:

• Histopathological different diagnosis than LPP.
• Inability to adhere to the study protocol, including medication intake, clinic visits, and questionnaire completion.
• Patients who are ineligible for the HCQ arm (due to contraindications), are automatically included in the MTX arm.
• Contraindications HCQ:

retinopathy and/or maculopathy

myasthenia gravis

body weight less than 35 kg

Patients who are ineligible for the MTX arm (due to contraindications), are automatically included in the HCQ arm.

- Contraindications MTX:

Conception (both male and female) and lactation

Severe kidney or liver dysfunction (fibrosis, cirrhosis) or alcohol abuse

Bone marrow hypoplasia, immunodeficiency

Anemia, leukopenia, or thrombocytopenia

Poor nutritional status (low albumin)

Hypersensitivity or allergy to MTX

Lung toxicity due to MTX or significant reduction in lung function.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Hydroxychloroquine (HCQ); HCQ is administered orally at a dosage of 400 mg daily.	Drug: Hydroxychloroquine; HCQ (15) is administered orally at a dosage of 400 mg daily.
Methotrexate (MTX); MTX is given at a dose of 15 mg per week, orally or subcutaneously. Additionally, folate supplementation is administered concurrently as part of standard care, with folate 10 mg/week administered 24 hours after MTX intake.	Drug: Methotrexate; MTX (16) is given at a dose of 15 mg per week, orally or subcutaneously. Additionally, folate supplementation is administered concurrently as part of standard care, with folate 10 mg/week administered 24 hours after MTX intake.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LPPAI	The main study parameter is the change in Lichen PlanoPilaris Activity Index (LPPAI) measured at 6 months (0-10).	at 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LPPAI	The main study parameter is the change in Lichen PlanoPilaris Activity Index (LPPAI) measured (0-10).	at 0, 12, 36, 48 weeks
Skindex-29	Quality of Life	at 0, 12, 24, 36, 48 weeks
Side effects	Number of side effects	at 0, 12, 24, 36, 48 weeks

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Investigators: Principal Investigator: DirkJan Hijnen, MD, PhD, Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: July 16, 2024
• First Submitted That Met QC Criteria: July 16, 2024
• First Posted (Actual): July 22, 2024

Study Record Updates

• Last Update Posted (Actual): July 22, 2024
• Last Update Submitted That Met QC Criteria: July 16, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Methotrexate; Hydroxychloroquine; Lichen planopilaris; Cicatricial alopecia
• Additional Relevant MeSH Terms: Skin Diseases; Pathological Conditions, Anatomical; Skin Diseases, Papulosquamous; Hypotrichosis; Hair Diseases; Lichenoid Eruptions; Alopecia; Lichen Planus; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate; Hydroxychloroquine
• Other Study ID Numbers: 11940

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Undecided

Drug and device information, study documents

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