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Lenalidomide vs Methotrexate in Difficult-to-treat Cutaneous Lupus Erythematosus

NCT06965244 · Status: NOT_YET_RECRUITING · Phase: PHASE3 · Type: INTERVENTIONAL · Enrollment: 122

Last updated 2025-05-11

No results posted yet for this study

Summary

Cutaneous lupus erythematosus (CLE) is a heterogeneous inflammatory autoimmune disease associated or not with systemic lupus erythematosus (SLE). Active CLE often cause pain/burning sensation and may lead to permanent visible scars and cicatricial alopecia, with psycho-social consequences/poor quality of life. First-line antimalarials (AMs) are recommended in CLE in addition to topical corticosteroids/tacrolimus with long-term response rate around 50%. Oral glucocorticosteroids (GCs) are recommended in addition to AMs for short term therapy in severe or widespread active CLE lesions. In non-responders to AMs and low-dose oral GCs, i.e., difficult-to-treat CLE, guidelines recommend the add-on of methotrexate as preferential second-line agent, with an overall efficacy of 50% in observational studies. Thalidomide has shown response rate of ≈90% in CLE in a meta-analysis of observational studies and is recommended as a second or third-line agent. However, potential severe adverse events (AEs) including teratogenicity, peripheral neuropathy and thromboembolic events limit its use.

Biological therapies including belimumab and anifrolumab, are approved only for patients with associated SLE (and not for those with isolated CLE). Their efficacy has been demonstrated as add-on therapy versus placebo but not versus a comparative drug. Moreover, efficacy of belimumab seems limited in difficult to-treat CLE and has not been assessed using validated tool, as the Cutaneous Lupus Erythematosus Disease Area and Severity (CLASI) Index. Anifrolumab seems interesting in CLE associated with SLE, but its use is limited by monthly intravenous infusions, high cost and unknown long-term AEs. Moreover, its efficacy in isolated CLE has not been assessed.

Lenalidomide is a thalidomide analogue with in vitro 1000 more potent immunomodulatory properties. It is recommended as a third-line treatment in France. With more than 60 treated patients, it showed excellent and rapid efficacy with an absence of drowsiness and peripheral neuropathy with a low-dose regimen of 5 mg/day. The use of lenalidomide was to date limited by its very high cost and its indications were restricted to haematological disorders. For note, the prevention of the higher risk of thromboembolism with lenalidomide requires the daily use of low-dose aspirin.

In France, a generic of lenalidomide is now available with a monthly cost of 2 euros, allowing a broad-scale assessment of its efficacy. Finally, lenalidomide might have a better efficacy than methotrexate.

We hypothesize that lenalidomide would be more efficacious than methotrexate in difficult-to-treat CLE patients with or without associated SLE. We assume that such trial would not be supported by pharmaceutical companies.

Conditions

  • Cutaneous Lupus Erythematosus (CLE)

Interventions

DRUG

Lenalidomide

Lenalidomide with oral dose of 5 mg/day during 16 weeks associated with low-dose aspirin of 100 mg/day except for patients already receiving anticoagulant therapy

DRUG

Methotrexate (MTX)

Methotrexate oral dose of 15 mg per week for individuals \< 80 kg, and a dose of 20mg per week for those over 80 kg, along with an equal dose of folic acid supplementation given 48 hours after each dose

Sponsors & Collaborators

  • Assistance Publique - Hôpitaux de Paris

    lead OTHER

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2025-10-01
Primary Completion
2029-02-01
Completion
2029-04-01

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT06965244 on ClinicalTrials.gov