Vergunst CE et al. (2007) Blocking the receptor for C5a in patients with rheumatoid arthritis does not reduce synovial inflammation. Rheumatology 46: 1773–1778

In rheumatoid arthritis (RA), the synovial compartment is infiltrated by a variety of immune cells. One factor that seems to be involved is C5a, a protein involved in chemotaxis. Theoretically, blocking C5a receptor (C5aR) activity could form a therapeutic strategy for RA. The recently developed cyclic peptide AcF-[OpdChaWR] (PMX53) competes effectively with C5aR without causing agonist effects. Preliminary results in rats suggest that PMX53 reduces the symptoms of experimental arthritis, and Vergunst et al. have investigated its potential as a therapeutic agent for RA in a proof-of-concept trial.

A total of 21 RA patients participated in a double-blind, placebo-controlled, phase Ib clinical trial. Orally administered PMX53 was assessed for safety, and its ability to reduce synovial inflammation was determined. The mean serum concentration of PMX53 achieved—40.8 nmol/h/l—has been shown in vitro to block C5aR-mediated cell activation. When synovial tissue obtained after 28 days of treatment was compared with that obtained at baseline, however, no changes in cell infiltration or key biomarkers were detected. The treatment group showed no clinical improvement, or even a trend towards it, and there was no correlation between the serum level of PMX53 and clinical response in individual patients.

Despite reaching serum levels high enough for C5aR-blocking activity, treatment of human patients with PMX53 did not reduce synovial inflammation. The authors conclude that C5aR blockade by PMX53 does not reduce synovial inflammation in human patients with RA.