To study the effect of silymarin against methotrexate-induced liver injury in rheumatic diseases including rheumatoid arthritis, psoriatric arthritis and psoriasis

- Methotrexate was indeed a common and effective treatment for rheumatoid arthritis, psoriatic arthritis and psoriasis. Methotrexate-related hepatotoxicity are common occur 1:1,100 persons. Liver abnormalities varies from asymptomatic liver enzyme elevation to fatal hepatic necrosis and liver fibrosis. Methotrexate was discontinued owing to liver dysfunction in 7.4%

Inclusion Criteria:

• Aged > 20 years

• Diagnosis at least one of the following

  1. Rheumatoid arthritis according to American College of Rheumatology/ The European Alliance of Associations for Rheumatology 2010(ACR/EULAR2010) with at least one joint swelling or tenderness or
  2. Psoriatric arthritis according to CASPAR classification criteria with at least one joint swelling or tenderness, or at least one site dactylitis or enthesitis or Psoriasis by dermatologist with active skin lesion
  3. No previous treatment with methotrexate or treatment with methotrexate within 30 day before randomization
  4. No previous treatment with other conventional synthetic DMARDs other than methotrexate such as sulfasalazine, hydroxycholoquine, leflunomide
  5. No previous treatment with biologic DMARDs such as anti-TNF
  6. Can follow the treatment protocal

Exclusion Criteria:

• Pregnancy or planning for pregnancy
• Breastfeeding women
• Ongoing treatment with active malignancy
• GFR < 30 ml/min/1.73m2
• Previous documented of HIV infection
• Chronic alcohol drinking ≥ 3 times/wk or drug abuse within 6 months prior to randomization
• Positive of HbsAg, anti HCV
• Previous documented of preexisting liver disease such as alcoholic liver disease, liver cirrhosis, autoimmune hepatitis
• AST or ALT > ULN ( 0-50 U/L )
• WBC < 3,000/ul or platelet < 100,000 /ul, ANC < 1,500/ul
• ILD diagnosed by rheumatologist and pulmonologist from chest X ray and HRCT
• History documented silymarin hypersensitivity or severe adverse effects diagnosed by physician or pharmacist from PMK hospital or from history drug allergy or symptoms such as rash, chest tightness, dyspnea, diarrhea and hypotension
• Cannot follow up on treatment protocal

Study Protocol is to be shared with others. Full data would become available by mid 2026.

mid 2026

IPD Sharing Access Criteria has not been decided.