Rheumatoid arthritis
Conditions
Interventions
Patients will be randomized to treatment with either add-on adalimumab s.c. 40
mg biweekly for 24 weeks or add-on Filgotinib 200 mg p.o. once daily for 24
weeks. *Add-on* means that patients will co
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a subject must meet all of the following criteria. Each patient must: - have a diagnosis of RA and must have fulfilled the revised 2010 EULAR/ACR criteria for classification of RA prior to initiation of first-line treatment. - have a positive test for the presence of anti-citrullinated protein antibodies (ACPA) in serum with a value of at least 200 U/ml, as determined by routine clinical assay. - have moderate to highly active disease defined by a disease activity score evaluating 28 joints (DAS28) >= 3.2 or, correspondingly, an sDAI score of > 11. - have used methotrexate therapy at a maximally tolerated dose once weekly for at least 1 month; concomitant glucocorticoid therapy is allowed if at a stable dose of = 4000 cells/µL, platelet count >= 150000/µL, and haemoglobin >= 10 g/dL (corresponding to 6.2 mmol/L) - have a serum creatinine clearance of >15 ml/min - be at least 18 years of age - if female and of childbearing potential, agree to: comply with effective contraceptive measures, use adequate contraception since the last menses and use adequate contraception during the study - be willing to undergo pre-treatment screening for latent tuberculosis infection by chest X-ray and Mantoux testing as well as serological screening for chronic viral hepatitis infection. As an alternative for the Mantoux test, a standardized IFN-gamma release assay may be used to assess latent tuberculosis infection. - be able and willing to give written informed consent prior to entry in the study.
Exclusion criteria
Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study. Any patient who: - has ever been treated with rituximab or another B-cell depleting agent - has been treated with a biological DMARD (except rituximab) or a targeted synthetic DMARD within 3 months prior to entry in the study - has received intra-articular or systemic glucocorticoid injections within 30 days prior to baseline or requires narcotic analgesics other than those accepted by the investigator for analgesia (e.g. paracetamol, NSAIDs, codeine, tramadol) * has been tested negative for ACPA * is in clinical remission as defined by a disease activity score evaluating 28 joints (DAS28) = 3 x upper limit of normal range) * has concurrent treatment with an experimental drug or who has participated in another clinical trial with an investigational drug within 30 days prior to study entry * has past or current history of solid or haematological neoplasms, except for curatively treated non-melanoma skin cancer, adequately treated in situ carcinoma of the cervix or another cancer curatively treated and with no evidence of disease for at least 10 years * is pregnant or a currently nursing woman * is, female and of childbearing potential, unwilling to use adequate contraceptive measures during the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is the change from baseline in the frequency of ACPA-expressing B cells secreting ACPA-IgG in ex-vivo PBMC cultures at the 24 week time-point compared between the two treatment arms. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary objectives are designed to define the changes to the auto-reactive B cell compartment induced by filgotinib versus control treatment in relation to the clinical context and to define/elucidate the mode of action of filgotinib with regard to these changes. | — |
Countries
Netherlands
Outcome results
None listed