TY - JOUR T1 - Clinical evidence for utilization of the A3 adenosine receptor as a target to treat rheumatoid arthritis: data from a phase II clinical trial. JF - The Journal of Rheumatology JO - J Rheumatol SP - 41 LP - 48 VL - 35 IS - 1 AU - Michael H Silverman AU - Vibeke Strand AU - Doron Markovits AU - Menachem Nahir AU - Tatiana Reitblat AU - Yair Molad AU - Itzhak Rosner AU - Michael Rozenbaum AU - Reuven Mader AU - Muhamad Adawi AU - Dan Caspi AU - Moshe Tishler AU - Pnina Langevitz AU - Alan Rubinow AU - Joshua Friedman AU - Lesly Green AU - Amir Tanay AU - Avivit Ochaion AU - Shira Cohen AU - William D Kerns AU - Ilan Cohn AU - Sari Fishman-Furman AU - Motti Farbstein AU - Sara Bar Yehuda AU - Pnina Fishman Y1 - 2008/01/01 UR - http://www.jrheum.org/content/35/1/41.abstract N2 - OBJECTIVE: Adenosine exerts antiinflammatory effects via activation of the A3 adenosine receptor (A3AR), a Gi protein-associated cell-surface receptor, overexpressed in synovial tissue and peripheral blood mononuclear cells (PBMC) in patients with active rheumatoid arthritis (RA). CF101 is a highly specific orally bioavailable A3AR agonist. METHODS: This was a multicenter study, blinded to dose, designed to assess the clinical activity and safety of CF101 in active RA. Seventy-four patients were randomized to receive 0.1, 1.0, or 4.0 mg CF101 bid for 12 weeks. The primary efficacy endpoint was American College of Rheumatology 20% response (ACR20) at Week 12. A3AR expression levels were analyzed in PBMC from 18 patients. 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 adverse events. Statistically significant correlations between A3AR overexpression at baseline and ACR50 and ACR70 responses were observed. CONCLUSION: CF101 administered bid for 12 weeks resulted in improvement in signs and symptoms of RA that did not achieve statistical significance, and was safe and well tolerated. The expression level of A3AR was directly correlated with patient responses to CF101, suggesting its utilization as a biomarker for the pharmacodynamic and therapeutic effects of this novel agent. These findings require confirmation in a double-blind randomized placebo-controlled trial, currently under way. ER -