Their active RA had an ACR functional class of 1 to 3 and a duration of at least 6 months. In addition, patients exhibited at least 8 66 swollen joints, at least 10 68 painful joints and at least one of the following three conditions, erythrocyte sedi mentation rate of at least free overnight delivery 28 mm hour, C reactive protein of at least 15 mg litre or morning stiffness for at least 45 minutes at both screening and baseline time Inhibitors,Modulators,Libraries points. The main exclusion criteria were patients with inadequate bone marrow function and a platelet count of not more than 100 �� 109 litre, active current infection, history of infec tion requiring hospitalisation, history of recurrent infections or treatment with antibiotics within 2 weeks of screening.

Treat ment washout or exclusion periods observed prior to entry to the study were DMARD use within 4 weeks, five half lives or washout in accordance with a specific drug any live vaccines taken within 4 weeks, use of more than one nonsteroidal anti inflamma tory drug or change of its dosage within 4 weeks, dosage of prednisone or equivalent corticosteroid of greater than Inhibitors,Modulators,Libraries 10 mg day or any dosage Inhibitors,Modulators,Libraries change within 4 weeks, and dosage of prednisone or equivalent corticosteroid of greater than 20 mg administered via intra articular injection or bolus intramuscular or intravenous treatment within 4 weeks. Other exclusion criteria included any previous use of recombinant IL1 receptor antagonist and patients who were preg nant or nursing. Study design and drug product This was a multicentre, prospective, uncontrolled, open label, randomised, dose ranging, phase 2a study of masitinib in adults with active RA, who were followed over the course of a 12 week period.

The study was approved by the local ethics committees Inhibitors,Modulators,Libraries and was carried out in compliance with the Dec laration of Helsinki and good clinical practices guidelines. Written Inhibitors,Modulators,Libraries informed consent was obtained from all patients. The study was registered in ClinicalTrials. gov under the trial regis sellectchem tration number NCT00831922. Masitinib, supplied as 100 and 200 mg tablets, was administered orally in two daily intakes. To evaluate the dose response of masitinib in DMARD refractory active RA, dose ranging was performed by randomly assigning patients to one of two initial treatment groups of 3 and 6 mg kg per day. Dosage could be increased by 1. 5 mg kg per day at weeks 4 and 8 in the event of insufficient response accompanied by minimal toxicity. Likewise, the dose could be reduced by 1. 5 mg kg per day or treatment discon tinued in case of serious adverse events.