Comparison of Combination Disease Modifying Antirheumatic Drugs With Methotrexate Therapy in Early Rheumatoid Arthritis

Jawaharlal Institute of Postgraduate Medical Education & Research

Status and phase: Completed; Phase 4

Conditions: Rheumatoid Arthritis

Treatments: Drug: Hydroxychloroquine; Drug: Leflunomide; Drug: Methotrexate; Drug: Folic Acid; Drug: Prednisolone

Study type: Interventional

Funder types: Other

Identifiers

NCT02644499

JIP/IEC/SC/2013/5/433

Details and patient eligibility

About

This study will be conducted to find out how well a patient of rheumatoid arthritis (RA) will respond to disease-modifying antirheumatic drugs (DMARDs). RA is a chronic inflammatory arthritis, which leads to joint damage & disability if not treated properly. A DMARD is used to treat RA that slows down or prevents joint damage, as opposed to just relieve pain or inflammation by painkillers. The study will be conducted at the Department of Clinical Immunology, JIPMER (Jawaharlal Institute of Postgraduate Medical Education & Research). Patients will receive either a single DMARD (Methotrexate) or combination DMARDs therapy (Methotrexate + Leflunomide + Hydroxychloroquine). During treatment course, routine blood investigations will be carried out to monitor treatment response and side effects.

Full description

Patients aged ≥18 years, fulfilling the 2010 ACR EULAR criteria for RA (symptom duration less than one year) & having moderate to severe disease activity (DAS28≥3.2) will be invited to participate. After providing written informed consent, eligible patients will be stratified into two groups. Block randomization will be done to generate random allocation sequence.

Treatment Group I will be treated with Methotrexate (MTX) monotherapy and Treatment Group II will be treated with Methotrexate + Leflunomide (LEF) + Hydroxychloroquine (HCQ) combination therapy. Concurrent treatment with non-steroidal anti-inflammatory drugs in adequate dose and oral low dose Glucocorticoids (GC) (max: 15 mg/d) will be allowed during the study.

DMARD dosages used are: MTX 25 mg/week orally (dosage after 6 weeks), LEF 20 mg/day (dosage after 2 weeks) and HCQ 400 mg/day. GCs will be given in an oral tapering scheme. All patients will be prescribed folic acid (10 mg/week) during MTX prescription.

Enrollment: 186 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age > 18 years satisfying 2010 ACR (American college of rheumatology) - EULAR criteria for RA
2. Arthritis in one or more joint (s)
3. Symptom duration <1 year
4. DMARD naive
5. Patients with moderate to severe disease activity (DAS28 ≥3.2)

Exclusion criteria

1. Disease in Remission/inactive disease (DAS28 criteria)
2. End stage disease (deformed fixed joints)
3. Patients with vasculitis or other severe extra-articular features
4. Contraindications to DMARD therapy (Chronic Alcoholism, Chronic liver disease, Evidence of acute/chronic infection, Chronic kidney disease, Patients with leucopenia (<3.0×109/l), thrombocytopenia (<150×109/l), aspartate aminotransferase (AST)/alanine aminotransferase (ALT)>2× upper normal value and creatinine level >150 μmol/l )
5. Pregnant, lactating females or inadequate contraception
6. Patients unable to come for regular follow up

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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186 participants in 2 patient groups

Combination therapy

Active Comparator group

Description:

Combination of Methotrexate (up to 25 mg per week), Leflunomide (20 mg once a day) and Hydroxychloroquine (200-400 mg once at night). All drugs are to be taken orally. Duration of therapy is for 3 months. All patients will receive folic acid (5 mg twice a week) along with methotrexate. Low dose prednisolone (weeks 1-2: 15 mg/day, weeks 2-4: 10 mg/day, weeks 4-6: 5 mg/day and weeks 6-8: 2.5 mg/day then stop) will be given as bridging therapy.

Treatment:

Drug: Prednisolone

Drug: Folic Acid

Drug: Methotrexate

Drug: Hydroxychloroquine

Drug: Leflunomide

Monotherapy

Active Comparator group

Description:

Methotrexate (up to 25 mg once a week) for 3 months. All patients will receive folic acid (5 mg twice a week) along with methotrexate. Low dose prednisolone (weeks 1-2: 15 mg/day, weeks 2-4: 10 mg/day, weeks 4-6: 5 mg/day and weeks 6-8: 2.5 mg/day then stop) will be given as bridging therapy.

Treatment:

Drug: Prednisolone

Drug: Folic Acid

Drug: Methotrexate