Rheumatoid arthritis.
Conditions
Interventions
Vaccinatie met KLH, Tetanus vaccine, Hepatitis A vaccine, pneumo 23, Mencevax ACWY en poliomyelitisvaccin.
Sponsors
Philip Remans, MD,PhD, Division of Clinical Immunology and Rheumatology, Hans Schipper, MD, PhD, Department of Internal Medicin, Theo Out, PhD, laboratory of Medical Immunology, René Lutter, PhD, Department of Experimental immunology, Ruth klaasen, MD, Division of Clinical Immunology and Rheumatology, Danielle Gerlag, MD, Division of Clinical Immunology and Rheumatology, Paul P. Tak, MD, PhD, Professor of Medicine.
Eligibility
Inclusion criteria
Inclusion criteria: 1. Able and willing to give written informed consent; 2. A diagnosed according to the revised 1987 criteria of the American College of Rheumatology (ACR) for at least 3 months; 3. Age 18-85 years; 4. Eligible for anti-TNF á therapy (according to the Dutch guidelines) or eligible for rituximab therapy; 5. Use of concurrent dmard therapy is allowed, provided the dose and frequency have been stable for at least 28 days. Subjects may be taking nonsteroidal anti-inflammatory drugs, provided the dose and frequency have been stable for at least 28 days. Subjects may be receiving prednisone therapy  10 mg/day provided that the dosage has been stable for at least 2 months prior to entry.
Exclusion criteria
Exclusion criteria: 1. A positive PPD skin test (> 4 mm induration); 2. Pregnancy; 3. Breastfeeding; 4. A history of or current acute inflammatory joint disease of different origin e.g. mixed connective tissue disease, seronegative spondylarthropathy, psoriatic arthritis, Reiter’s syndrome, systemic lupus erythematosus or any arthritis with onset prior to age 16 years; 5. Acute major trauma; 6. Therapy within the previous 60 days with: any experimental drug,alkylating agents, e.g. cyclophosphamide, chlorambucil, monoclonal antibodies (including infliximab and etanercept), growth factors, or other cytokines; 7. Therapy within the previous 28 days with: parenteral or intra-articular corticoid injections, oral corticosteroid therapy exceeding a prednisone equivalent of 10 mg daily; 8. HIV infection; 9. History of severe allergic or anaphylactic reactions to vaccines; 10. Vaccination with KLH, Pneumovax, Meningovax, Polio or tetanus toxoid in the past 12 months; 11. Fever (orally measured > 38 °C), chronic infections or infections requiring anti-microbial therapy Other active medical conditions such as inflammatory bowel disease, bleeding diathesis, or severe unstable diabetes mellitus; 12. Manifest cardiac failure (stage III or IV according to NYHA classification); 13. Progressive fatal disease/terminal illness; 14. Congenital or acquired (known HIV-positive status) immunodeficiency; 15. History of lymphoproliferative disease or treatment with total lymphoid irradiation; 16. White cell count less than 3.5 x 109/l; 17. Platelet count less than 100 x 109/l; 18. Haemoglobin of less than 5.3 mmol/l; 19. Body weight of less than 45 kg; 20. History of drug or alcohol abuse; 21. Any concomitant medical condition which would in the investigator’s opinion compromise the patient’s ability to tolerate, absorb, metabolize or excrete the study medication; 22. Inability to give informed consent; 23. Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of patients with positive response to vaccination prior and post adalimumab or rituximab therapy, and measured 4 weeks after administration of the vaccins. Response is defined as a 2-fold increase in antibody levels to the administered antigens or as an absolute change in specific antibody of 1 g/mL, or seroconversion in patients with a non-protective baseline level of antibodies (<1/40). | — |
Secondary
| Measure | Time frame |
|---|---|
| To analyse the effect of vaccination on RA disease parameters and the influence of adalimumab and rituximab therapy on T and B cell response after vaccination, as well as the relation T-B cell response. This will be done by analyzing T and B cell subsets, T cell cytokine production to specific antibody stimulus measured by elispot and immunoglobuline subtypes. | — |
Contacts
Public ContactP.P. Tak
Academic Medical Center (AMC), Department of Clinical Immunology and Rheumatology, P.O. Box 22660
Outcome results
None listed