Clinical evidence for utilization of the A3 adenosine receptor as a target to treat rheumatoid arthritis: Data from a phase II clinical trial

Michael H. Silverman, Vibeke Strand, Doron Markovits, Menachem Nahir, Tatiana Reitblat, Yair Molad, Itzhak Rosner, Michael Rozenbaum, Reuven Mader, Muhamad Adawi, Dan Caspi, Moshe Tishler, Pnina Langevitz, Alan Rubinow, Joshua Friedman, Lesly Green, Amir Tanay, Avivit Ochaion, Shira Cohen, William D. KernsIlan Cohn, Sari Fishman-Furman, Motti Farbstein, Bar Bar Yehuda, Pnina Fishman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

120 Scopus citations


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.

Original languageEnglish
Pages (from-to)41-48
Number of pages8
JournalJournal of Rheumatology
Issue number1
StatePublished - Jan 2008
Externally publishedYes


  • A adenosine receptor
  • Clinical trials
  • Rheumatoid arthritis


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