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

Inclusion criteria

• Patients of at least 18 years of age
• Affiliated to the French social security
• Able to provide written informed consent
• Histologically-confirmed diagnosis of active CLE with or without associated SLE, either historical or at screening
• CLASI-A score ≥ 8 at both screening and randomization
• Active CLE despite

• AMs agents used for at least 3 months and at stable dose for at least 30 days prior to randomization or previously documented discontinuation of AMs due to poor tolerability an/or side effect and/or
• stable dose of GCs ≤15mg/day and/or
• stable dose of topical corticosteroids (TCS) or topical tacrolimus for at least 30 days prior to randomization
• Accepting monthly plasma pregnancy test and using adequate contraception for at least 4 weeks before and until 4 weeks following treatment

Exclusion criteria

• Kidney function, liver function, cell blood count and infectious serology incompatible with receiving the study treatments, according to the SMPC of each drug.
• Alcoholism (1/ no more than 10 standard drinks per week, 2/ no more than two standard drinks per day, and 3/ at least two alcohol-free days every week)
• Ongoing cancer, including solid tumors and hematologic malignancies
• Active severe SLE features including lupus nephritis, neuropsychiatric SLE, serositis, severe haematological features (autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura) requiring high dose oral or IV GC and/or mycophenolate mofetil or cyclophosphamide
• Medications:

• Previous failure of methotrexate and lenalidomide prescribed for active CLE
• Use of classical immunosuppressant drugs (mycophenolate mofetil, azathioprine), thalidomide, dapsone, retinoids, Janus Kinase inhibitors for CLE or SLE 4 weeks before screening
• Use of biological therapy for CLE or SLE (including belimumab, rituximab, obinituzumab, ustekinumab, anifrolumab) 12 weeks before screening
• Contraindication to use low-dose aspirin: salicylate hypersensitivity, salicylate-induced asthma, constitutional or acquired bleeding disorder, active gastroduodenal ulcer, or history of digestive bleeding.
• Arterial or unprovoked venous thromboembolic events ≤ 5 years (for note antiphospholipid syndrome treated with vitamin K antagonist without thromboembolic events in the last 5 years or patients with positive antiphospholipid autoantibodies will NOT be excluded)
• Pregnant women, breastfeeding or planning to become pregnant during the study treatment period and 1 month after the last dose of study treatment
• Patients under legal protection and inability to comply with study requirement