Rheumatoid arthritis refractory to standard disease modifying agents
Conditions
Interventions
Rituximab infusions
Sponsors
A Bour & Company (Ltd)
Eligibility
Inclusion criteria
Inclusion criteria: 1.18-65 years of age 2. must fulfill the revised 1987 American Rheumatism association criteria for at least 6 months 3.Swollen joint count ³4 (28 joint count) and tender joint count ³4(28 joint count at screening and baseline 4.CRP ³6 mg/L OR ESR ³28 mm/h at screening 5. Patients who used methotrexate at 15-25 mg/wk for at least 12 weeks without response. This will include patients who failed to respond to additional treatment with either or both SSZ, chloroquine. patients who have used leflunomide will not be included 6.The doses of MTX must be stable for 4 weeks prior to baseline 7.Prednisolone <10 mg/day or equivalent glucocorticoids are permitted if dose stable for 4 weeks prior to baseline 8.Patients will be allowed to receive non-steroidal anti-inflammatory drugs if dose stable for ³4weeks prior to baseline 9.A negative serum pregnancy test at screening for female subjects of childbearing potential. Use of contraception in patients of reproductive potential
Exclusion criteria
Exclusion criteria: • History of or current inflammatory joint disease other than RA or other systemic rheumatic disorder • Patients with functional class IV according to ACR classification of functional status • Known hypersensitivity to any component of the tetanus toxoid adsorbed vaccine • Evidence of significant uncontrolled concomitant disease, such as diseases of heart, liver, lung, nervous system, renal, endocrine, or gastrointestinal disorders • Known active bacterial, viral, fungal, mycobacterial, or other infection or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of Day 1 or oral antibiotics within 2 weeks of Day 1 • History of serious recurrent or chronic infection history of deep space/tissue infection within 52 weeks prior to baseline. History of or currently active primary or secondary immunodeficiency, including HIV infection • History of cancer, including solid tumors and hematological malignancies • History of alcohol, drug, or chemical abuse within the 6 months prior to screening • Diagnosis of juvenile idiopathic arthritis/juvenile rheumatoid arthritis before age 16 • Immunization with a live vaccine within 4 weeks prior to randomization (Day 1) • Serum creatinine > 1.4 mg/dl for women or > 1.6 mg/dl for men • AST or ALT > 2.5 times upper limit of normal • Platelet count < 100,000/ml • Hemoglobin < 8.0 g/dl • Neutrophils < 1.5x10^3/ml • Positive tests for hepatitis B surface antigen • Levels of IgG < 5.0 mg/ml and/or IgM = 0.4 mg/ml
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| (ACR) 20% improvement of response(ACR 20) at 24 weeks [6 months, 1 year and two years after the first infusion of drug] Disease activity score 28 (DAS 28) improvement at 24 weeks [6 months, 1 year and two years after the first infusion of drug] | — |
Secondary
| Measure | Time frame |
|---|---|
| ACR50 and ACR70 improvement atweek 24, 1 year and 2 years [6 months, 1 year and two years after the first infusion of drug] Immunological markers which include rheumatoid factor, B cells (CD 19) and T-cell (CD3,CD27) and immunoglobulin levels (IgG,IgM,IgA) [6 months, 1 year and two years after the first infusion of drug ] Side effects noted with rituximab and leflunomide, particularly the rate of infections [6 months, 1 year and two years after the first infusion of drug ] The antibody response to tetanus toxoid and pneumococcal vaccine given at 36 weeks [6 months, 1 year and two years after the first infusion of drug ] | — |
Countries
Sri Lanka
Contacts
Public ContactDr. Lalith S. Wijayaratne MBBS, MD, MRCP
Consultant Rheumatologist,
Outcome results
None listed