IMPROVED: Induction therapy with Methotrexate and Prednisone in Rheumatoid Or Very Early arthritic Disease

INTERVENTION:

Product Name: Methotrexate Product Code: MTX Pharmaceutical Form: Tablet INN or Proposed

INN:

METHOTREXATE CAS Number: 59052 Current Sponsor code: MTX Concentration unit: mg milligram(s) Concentration type: up to Concentration number: 30‐ Product Name: Prednisone Pharmaceutical Form: Tablet INN or Proposed

INN:

PREDNISONE CAS Number: 53032 Concentration unit: mg milligram(s) Concentration type: range Concentration number: 7,5‐60 Product Name: Sulfasalazine Pharmaceutical Form: Tablet INN or Proposed

INN:

SULFASALAZINE CAS Number: 599791 Current Sponsor code: SSZ Concentration unit: mg milligram(s) Concentration type: up to Concentration number: 2000‐ Trade Name: hydroxychloroquine Product Name: hydroxychloroquine Product Code: HCQ Pharmaceutical Form: Tablet INN or Proposed

INN:

HYDROXYCHLOROQUINE SULFATE CAS Number: 747364 Current Sponsor code: HCQ Concentration unit: mg milligram(s) Concentration type: up to Concentration number: 400‐ Trade Name: Humira Product Name: adalimumab Pharmaceutical Form: Solution for injection

CONDITION:

rheumatoid arthritis and undifferentiated arthritis ; MedDRA version: 8.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis

PRIMARY OUTCOME:

Main Objective: The objectives of this study are:; •To determine the percentage of patients with recent‐onset RA and UA who achieve and maintain clinical remission on treatment with a combination of methotrexate 25 mg/week and extended prednisone pulse (tapered high dose) after 4 months. ; ; •To determine whether, if clinical remission is not achieved, methotrexate+prednisone combination therapy should be extended with sulphasalazine and hydroxychloroquine or switched to methotrexate+adalimumab combination therapy. ; Primary end point(s): Clinical remission according to a disease activity score (DAS) < 1.6, measured by research nurses at each follow‐up visit. The percentage of patients achieving clinical remission after 4 months with the initial therapy consisting of MTX and tapered high dose prednisone will be calculated. From the patients who were randomized to one of two treatment arms, the percentage achieving clinical remission after one year will be calculated. ; ; Functional ability will be measured by the Dutch Health Assessment Questionnaire (HAQ), a self‐administered questionnaire that evaluates the level of difficulty the patient is experiencing with activities of daily living (ADL) and the degree of assistance required by the patient. ; ; Radiological joint damage, absolute as well as progression from baseline, will be assessed on radiog¬raphs of the hands, wrists and feet at entry and one year later by the validated modified Sharp/van der Heijde score All radio¬graphs will be sent to the coordi¬na¬ting centre and viewed separate by two experienced rheumatologists, who are blinded for the treatment allocation. The radiographs will be presented in random order.; Secondary Objective: toxicity, costs, quality of life measurements

INCLUSION CRITERIA:

1. minimum age of 18 years 2. at least one swollen joint 3. at least one other painful joint 4. symptom duration shorter than 2 years 5. diagnosis rheumatoid arthritis according to the ACR classification criteria or 6. diagnosis undifferentiated arthritis, suspected for rheumatoid arthritis by the rheumatologist, as no classification criteria exist. 7. patients naive for treatment with corticosteroids and disease modifying anti‐rheumatic drugs (DMARDs). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range