None listed
Conditions
Interventions
GROUP 1 Type of group
This group will be treated with: Rituximab, at a dose of 500 mg, in IV infusion on days 1 and 15 of the treatment cycle, future infusions will be administered every 24 weeks up to a maximum of 3 years + Methylprednisolone, at a dose of 100 mg, in IV infusion for 30 minutes before each infusion of Rituximab + Methotrexate, in tablets, at a dose of 7.5 mg, which may be increased up to 30 mg, PO, once a week.
Group name:GROUP C Type of group
This group will be treated with: Rituximab Placebo, in IV infusion on days 1 and 15 of the treatment cycle, from week 104, Rituximab will be administered in a dose of 500 mg or 1000 mg IV, on days 1 and 15 of following treatment cycles + Methylprednisolone, at a dose of 100 mg, in IV infusion for 30 minutes before each infusion of Rituximab + Methotrexate, in tablets, at a dose of 7.5 mg, which may be increased up to 30 mg, PO, once per week.
Sponsors
F. HOFFMANN-LA ROCHE LTD.,
Eligibility
Inclusion criteria
Inclusion criteria: 1. Be willing to grant written informed consent and comply with the requirements of the study protocol. 2. Patients with active rheumatoid arthritis diagnosed for at least 8 weeks but not more than 4 years. 3. Virgin patients to, and considered to be candidates for, treatment with methotrexate. 4. Swollen joint count (SJC) ≥ 8, and Painful joint count (TJC) ≥ 8. 5. CRP ≥12 mg / dL. 6. From 18 to 80 years of age. 7. Glucocorticoids ≤ 10 mg / day of prednisolone or equivalent allowed if it is stable at least 4 weeks before the baseline visit. 8. The use of NSAIDs is allowed if it is stable for at least 2 weeks before the baseline visit. 9. For patients of reproductive age (men and women), use reliable contraceptive methods throughout their participation in the study. 10. They must agree to receive oral folate. 11. Only for RF negative patients: Radiographic evidence of at least one joint with erosion attributable to rheumatoid arthritis (RA). 12. Patients who are going to receive or who are currently receiving, treatment for RA as outpatients.
Exclusion criteria
Exclusion criteria: 1. Autoimmune rheumatic disease different from RA, or with significant systemic manifestations. 2. Functional class IV. 3. History of inflammatory joint disease different from RA. 4. Diagnosis of juvenile idiopathic arthritis before the age of 16 years. 5. Any surgical procedure. 6. Lack of peripheral venous access. 7. Pregnancy or breastfeeding, maternal. 8. Significant pulmonary or cardiac disease. 9. Evidence of significant uncontrolled concomitant disease. 10. Primary or secondary immunodeficiency. 11. Known active infection of any kind, or any significant episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks prior to the baseline visit or the termination of oral antibiotics within 2 weeks before the baseline visit. 12. History of deep tissue / space infections within 52 weeks before the baseline visit. 13. History of severe chronic or recurrent infection. 14. History of cancers. 15. Any vascular or systemic neurological disorder that could affect any of the efficacy evaluations. 16 Current alcoholism or drug addiction or history of drug addiction or alcoholism in the 24 weeks prior to the initial visit. 17. History of severe anaphylactic or allergic reaction to a biological agent or known hypersensitivity to any component of rituximab or to human proteins. 18. Pre-treatment with any biological agent under investigation or approved for RA. 19. Pre-treatment with an anti-alpha4 integrin antibody or costimulation modulator. 20 Concomitant treatment with a biological agent other than MTX. 21 Pre-treatment with any therapy to reduce cells. 22 Treatment with any agent under investigation within 28 days of the baseline visit or 5 half lives of the investigational medication. 23. The reception of any vaccine within 28 days prior to the baseline visit. 24. Parenteral or intra-articular glucocorticoids within the 4 weeks prior to the baseline visit. 25. Intolerance or contraindications to glucocorticoids IV. 26. Positive human chorionic gonadotropin. 27. Positive tests for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or serology for hepatitis C. 28. Hemoglobin 2.5 times the normal upper limit.
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:Criteria 1, 2 and 3: Separate radiographs of each posteroanterior (AP) hand and each anterior antero-posterior foot (AP). These images will be evaluated by the modified Sharp-Genant scale, which evaluates erosion and shortening of the joint space of both feet and hands. Criterion 4: Non-radiographic progression is defined as the change in the modified Sharp scale ≤ 0. Measure:Radiographic Criteria: 1) Change in the modified Sharp total scale to week 24 and 104. 2) Change in Sharp modified erosion scale to week 52. 4) Proportion of patients without radiographic progression at week 52. Timepoints:Weeks 24, 52 and 104. ; Outcome name:Criteria 1, 5, 6 - 10: Revised Criteria ACR, for the classification of the functional capacity of rheumatoid arthritis (Classes I - IV). Criteria 2 and 8: Activity scale composed of the evaluation of 28 articulations and the values ​​of the erythrocyte sedimentation rate. Criterion 3: Scale of the European League Against Rheumatism. Criterion 4: Functional Evaluation of Chronic Disease Therapy - Fatigue (FACIT), evaluates the degree of fatigue. Measure:Criteria of signs and symptoms: 1) Proportion of patients with ACR20 / ACR50 / ACR70 / ACR90 response. 2) Change in the scale of Disease Activity (DAS 28-ESR) to week 52. 3) Change in the proportion of EULAR response. 4) Change in fatigue scale FACIT. 5) All the secondary endpoints of Signs and Symptoms (ACR20 / ACR50 / ACR70 / ACR90, DAS 28-ESR, EULAR and FACIT fatigue) at week 24 and 104. 6) Proportion of patients with ACR20 / 50 response / 70/90 during the time. 7) Accumulated density function tables of ACRn. 8) Change in DAS28 CRP. 9) Changes in full ACR. 10) AUC of the ACRn. Timepoints:Criterion 1-9: Week 52. Criterion 10: Weeks 24, 52 and 104. ; Outcome name:Criteria 1 and 3: The Health Assessment Questionnaire - Index of Disability (HAQ-DI), is a 20 question instrument referring to the activities that th | — |
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Separate radiographs of each posteroanterior (AP) hand and each anterior anteroposterior (AP) foot. These images will be evaluated by the modified Sharp-Genant scale, which evaluates erosion and shortening of the joint space of both feet and hands. Measure:Change in the modified Sharp total scale. Timepoints:Week 52. | — |
Countries
Australia, Belgium, Brazil, Canada, China, Czech Republic, Denmark, Finland, France, Germany, India, Italy, Korea South, Mexico, Netherlands, Norway, Panama, Peru, Philippines, Poland, Romania, Russian Federation, Spain, United Kindgdom, United States
Outcome results
None listed