Abatacept to Silence anti-Citrullinated protein Antibody-expressing B cells in Rheumatoid Arthritis

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 46

Inclusion Criteria

- have a diagnosis of rheumatoid arthritis according to the revised 2010
EULAR/ACR criteria for classification of RA
- have a positive test for the presence of anti-citrullinated protein
antibodies (ACPA) in serum as determined by routine clinical assay.
- have adequate hematologic function (ANC * 4000 cells/µL, platelet count *
150000/µL, and hemoglobin * 10 g/dL (corresponding to 6.2 mmol/L)
- have serum creatinine concentrations < 1.5 mg/dl and/or a normal creatinine
clearance
- be at least 18 years of age
- if a female patient is of childbearing potential, agree to: comply with
effective contraceptive measures, use adequate contraception since the last
menses, use adequate contraception during the study, have a negative pregnancy
test within one week of study entry
- be willing to receive a booster vaccination against tetanus toxoid three to
four weeks prior to randomization
- be able and willing to give written informed consent prior to entry in the
study

Exclusion Criteria

- been previously treated with either abatacept and/or methotrexate or
another csDMARD
- been previously treated with a kinase inhibitor
- been previously treated with rituximab or another B-cell depleting agent
- been previously treated with a biological DMARD
- received intra-articular or systemic glucocorticoid injections or has
required treatment for acute RA flare (not being part of a regular therapeutic
regimen) within four weeks prior to randomization or requires narcotic
analgesics other than those accepted by the investigator for analgesia (e.g.
paracetamol, codeine, tramadol)
* been tested negative for anti citrullinated protein antibodies
* contraindications for a booster vaccination against tetanus toxoid prior to
randomization to the treatment arms; if a patient refuses booster vaccination
but has detectable numbers of tetanus toxoid-specific B cells circulating in
peripheral blood prior to the baseline visit, the patient can still be allowed
to participate in the study at the judgement of the investigator.
* evidence of any other major chronic inflammatory disease (i.e. psoriasis,
psoriatic arthritis, spondyloarthritis or inflammatory bowel disease)
* evidence of poorly controlled diabetes, history of clinically significant
pulmonary disease including interstitial lung disease or methotrexate-induced
lung disease, poorly controlled asthma or a history of severe life-threatening
asthma attacks, history of active tuberculosis, history of latent tuberculosis
without adequate medical treatment, liver cirrhosis or fibrosis, significant
active infection or any underlying diseases that could predispose the subject
to infections
* liver function abnormality (total bilirubin * 1.5 x the upper limit of normal
range, AST, ALT * 3 x upper limit of normal range)
* 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
* pre-existing sensory or motor polyneuropathy * Grade 2 according to NCI CTC
* past or current history of 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
* significant cardiac disease, cardiac arrhythmia (Lown Grade * III),
uncontrolled hypertension or recent history of myocardial ischemia
* Pregnant or nursing women

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint is the percentage of ACPA-expressing B cells circulating<br /><br>in peripheral blood of patients with early, ACPA-positive rheumatoid arthritis<br /><br>that express the proliferative marker Ki-67 at the 24 week time point in the<br /><br>two treatment arms.<br /><br>Outcome measure for the primary endpoint: flow cytometry*based determination of<br /><br>the percentage of ACPA-expressing B cells that stain positive for Ki-67.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The change from baseline in disease activity (expressed as DAS 44) at week 24.</p><br>

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