Comparison of Disease Modifying Antirheumatic Drugs Therapy in Patients With RA Failing Methotrexate Monotherapy
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Methotrexate; Leflunomide; Hydroxychloroquine; Prednisolone; Folic Acid; Sulfasalazine
Intervention description: Methotrexate, a structural analogue of folic acid, can be administered orally or parenterally to treat a variety of rheumatic diseases; Leflunomide inhibits pyrimidine synthesis, resulting in blockade of T-cell proliferation. Leflunomide is used in patients with moderate to severe active rheumatoid arthritis with early or late disease; Hydroxychloroquine (HCQ) is a well-tolerated DMARD that is commonly used in combination therapy regimens for RA. HCQ is more commonly used than chloroquine.; Low dose prednisolone (weeks 1-2: 7.5 mg/day, weeks 2-4: 5 mg/day, weeks 4-6: 5 mg on alternate day and then stop); Folic acid is to be given to all patients receiving methotrexate at a dose of 5 mg twice a week.; 5-aminosalicylic acid (5-ASA) is the active component of sulfasalazine; the specific mechanism of action of 5-ASA is unknown; however, it is thought that it modulates local chemical mediators of the inflammatory response, especially leukotrienes, and is also postulated to be a free radical scavenger or an inhibitor of tumor necrosis factor (TNF)
Intervention MeSH terms: Folic Acid; Hydroxychloroquine; Sulfasalazine; Prednisolone; Methotrexate; Leflunomide; Glucocorticoids
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 136.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      RA (Rheuatoid arthritis) is a multisystem disease that mainly involves joints resulting in
      destructive arthritis if not treated rapidly. Inspite of various advances in field of early
      diagnosis and treatment of RA, there is still a need for better understanding of the efficacy
      and safety of various combinations of conventional DMARDS, and to rank them in order
      accordingly, so as to give a clearer vision for further management of RA once MTX monotherapy
      fails, so as to achieve remission as soon as possible. The study will be conducted at the
      Department of Clinical Immunology, JIPMER (Jawaharlal Institute of Postgraduate Medical
      Education & Research). patients who fail methotrexate monotherapy will be randomised to 2
      treatment arms - either a combination of Sulfasalazine (SSZ), Hydroxychloroquine (HCQ) and
      Methotrexate (MTX) or Leflunomide (LEF), Hydroxychloroquine (HCQ) and Methotrexate (MTX)
    

Eligibility criteria:

        Inclusion Criteria:

        Age >18 years satisfying ACR-EULAR criteria for RA

          1. Polyarthritis (>4 joints)

          2. Disease duration of less than 2 years

          3. Patients with moderate to severe disease activity (DAS28>3.2)

          4. Patients who have failed to respond to initial Methotrexate monotherapy

        Exclusion Criteria:

          1. End stage disease (deformed fixed joints)

          2. Patients with vasculitis, extra-articular features like interstitial lung disease8

          3. 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), AST/ALT>2× upper normal value and
             creatinine clearance <30ml/minute )

          4. Pregnant, lactating women ; patients (both men and women) of reproductive age group
             unwilling for contraceptive use who have not completed the family

          5. Patients unable to come for regular follow up