Effect of Silymarin Against Methotrexate-induced Liver Injury in Rheumatic Diseases

Phramongkutklao College of Medicine and Hospital

Status: Enrolling

Conditions: Psoriasis; Psoriatic Arthritis; Rheumatoid Arthritis

Treatments: Drug: Placebo; Drug: Silymarin

Study type: Interventional

Funder types: Other

Identifiers

NCT06277635

TAPAC001

Details and patient eligibility

About

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

Full description

• 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%

Enrollment: 72 estimated patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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72 participants in 2 patient groups, including a placebo group

Silymarin group

Active Comparator group

Description:

Silymarin 140 mg oral tid pc + methotrexate weekly + folic acid 5 mg oral OD pc for 12 weeks

Treatment:

Drug: Silymarin

Placebo group

Placebo Comparator group

Description:

Placebo + methotrexate weekly + folic acid 5 mg oral OD pc for 12 weeks

Treatment:

Drug: Placebo