CCR5 blockade in rheumatoid arthritis: a randomised, double-blind, placebo-controlled clinical trial.
OBJECTIVE
C-C chemokine receptor type 5 (CCR5), a chemokine receptor expressed on T cells and macrophages, and its ligands are found in inflamed synovial tissue (ST) of patients with rheumatoid arthritis (RA). The rationale for testing CCR5 blockade in patients with RA was supported by the effects of a CCR5 antagonist in collagen-induced arthritis in rhesus monkeys. The effects of CCR5 blockade in patients with active RA were explored.


METHODS
In this phase Ib randomised, placebo-controlled trial, treatment with an oral CCR5 inhibitor (SCH351125) in patients with active RA was evaluated. Clinical efficacy was assessed using European League Against Rheumatism and American College of Rheumatology response criteria. ST biopsies were taken before and after 28 days of treatment, and analysed for CCR5+ cells. In a subset of patients, MRIs of an inflamed joint were obtained before and after treatment.


RESULTS
In all, 32 patients were included; 20 received SCH351125 and 12 placebo. Three patients who received SCH351125 did not complete the study due to adverse events; none of these were serious. No improvement was observed in the active treatment group compared to placebo. Results were consistent for clinical evaluation, ST analysis and MRI.


CONCLUSIONS
This proof of concept study does not support the use of CCR5 blockade as a therapeutic strategy in patients with active RA.
van Kuijk
Arno W R
AW
Academic Medical Center/University of Amsterdam, The Netherlands.
Vergunst
Clarissa E
CE
Gerlag
Danielle M
DM
Bresnihan
Barry
B
Gomez-Reino
Juan J
JJ
Rouzier
Regine
R
Verschueren
Patrick C
PC
van der Leij
Christiaan
C
van de Leij
Christiaan
C
Maas
Mario
M
Kraan
Maarten C
MC
Tak
Paul P
PP
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D065100:CCR5 Receptor Antagonists; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010091:Oximes; D010880:Piperidines / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D065100:CCR5 Receptor Antagonists; D003497:Cyclic N-Oxides; D010091:Oximes; D010880:Piperidines; D011725:Pyridines; C438583:Ancriviroc