Clinical evidence for utilization the A3 adenosine receptor as a target to treat rheumatoid arthritis: Data from a phase IIa clinical trial. Conference Paper uri icon


  • Background: Adenosine exerts anti-inflammatory effects via activation of the A3 Adenosine Receptor (A3AR), a Gi protein associated cell surface receptor, over-expressed in synovial tissue and peripheral blood mononuclear cells (PBMCs) in patients with active rheumatoid arthritis (RA). CF101 (1-Deoxy-1-[6- [(iodophenyl) methyl] amino] -9H-purine-9-yl]-N-methyl-(-D-ribofuranuronamide), (IB-MECA) is a highly specific orally bioavailable A3AR agonist. Objectives: A phase II study for assessing the early activity and safety of CF101 in patients with active RA. Methods: The study was a multi-center, double-blind study. 74 patients were randomized to receive 0.1, 1.0, or 4.0 mg CF101 BID for 12 weeks. The primary efficacy end point was ACR20 responses at week 12. A3AR expression levels at baseline were analyzed in PBMCs from 18 patients, utilizing Western blot analysis. Results: Maximal responses were observed with 1.0 mg BID; lower at 0.1 and 4.0 mg BID. At 12 weeks, 55.6%, 33.3% and 11.5% of the patients receiving 1.0 mg CF101 achieved ACR20, 50 and 70 responses, respectively. CF101 was generally well tolerated with mild headache (4.1%), nausea (2.7%) and rash (2.7%) being the most common treatment related AEs. A highly statistically significant (p<0.02) correlation between A3AR expression at baseline and the ACR50 and ACR70 responses was observed in the examined 18 patients. Conclusion: CF101 administered BID for 12 weeks resulted in improvement in signs and symptoms of RA, and appeared to be safe and well tolerated. The expression level of A3AR was demonstrated to be directly correlated with patient responses to CF101, suggesting its utilization as a biomarker for the pharmacodynamic effects of this novel therapeutic agent. These findings require confirmation in a double blind, randomized, placebo-controlled trial, currently underway

publication date

  • June 13, 2007