Rheumatoid arthritis, anti-IgE, IgE-ACPA, CCP
Conditions
Interventions
A prospective open single-center, phase IIa study investigating anti-IgE therapy (Omalizumab) in refractory IgE-ACPA+ RA patients.
We are administering subcutaneously monoclonal anti-IgE antibody (0
Sponsors
Leiden University Medical Center
Eligibility
Inclusion criteria
Inclusion criteria: 1. Patients with active rheumatoid arthritis (RA). These include patients with risk of permanent disability, irreversible major organ failure or premature mortality. Refractory disease is defined as persistent or relapsed disease activity despite conventional treatment, i.e. combination of disease modifying antirheumatic drugs including maximal tolerable doses of methotrexate. Active disease is defined as a DAS44 (Disease Activity Score of 44 joints) score of more than 2.4; 2. Presence of IgE-ACPA; 3. Age above 18 years; 4. WHO performance status 0, 1 or 2; 5. Informed consent according to rules and regulations of Leiden University Medical Center.
Exclusion criteria
Exclusion criteria: 1. History of allergic or anaphylactic reaction to a biological agent or known hypersensitivity to any component of anti-IgE monoclonal antibodies or to murine proteins; 2. Life expectation of less than 6 months; 3. History of severe CNS disturbances and psychiatric problems; 4. Severe uncontrolled infections including parasitosis; 5. Irreversible major organ dysfunction, defined by any of the following criteria: A. Creatinine clearance 6.7 kPa (>50 mmHg); E. Sustained 3-fold increase in serum transaminase or bilirubin. 6. HIV positivity.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Clinical parameters for disease activity are measured by the DAS44 (Disease Activity Score on 44 joints) assessment. Responses are classified as follows: A. Complete response is defined as a DAS44 < 1,6; B. Clinical complete response is defined as a DAS44 < 2,4 or fulfillment of EULAR criteria for „good improvement“; C. Clinical partial response is defined when EULAR criteria for „moderate improvement“ is fulfilled; D. Progressive disease is defined as DAS44 increasing or decreasing less than 10% from baseline; E. Non-response is defined as DAS44 increasing more than 10% of baseline after 1 month of treatment. 2. Immunological parameters in peripheral blood and synovium after treatment with anti-IgE antibodies (Omalizumab) are: A. Proportion of basophils, mast cells; B. Functional presence of IgE-ACPA; C. Production of auto-antibodies (ACPA isotypes); D. Synovial infiltration of plasmacells, mast cells and (IgE-)ACPA presence in synovial fluid. 3. Safety and toxicity parameters are evaluated according to WHO Common Toxicity Criteria. | — |
Contacts
Public ContactA.J.M. Schuerwegh
Leiden University Medical Center (LUMC)
Outcome results
None listed