title: Chemokine receptor CCR1 antagonist CCX354-C treatment for rheumatoid arthritis: CARAT-2, a randomised, placebo controlled clinical trial.
abstract: OBJECTIVE
  CCX354-C is a specific, orally administered antagonist of the C-C chemokine receptor 1, which regulates migration of monocytes and macrophages to synovial tissue. This clinical trial evaluated the safety and efficacy of CCX354-C in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  CARAT-2 is a 12-week double-blind, randomised, placebo controlled trial in 160 patients with RA, with 68 tender joint count and 66 swollen joint count ≥8 and C-reactive protein (CRP) >5 mg/l, despite being on methotrexate for at least 16 weeks. Subjects received placebo, CCX354-C 100 mg twice daily, or 200 mg once daily for 12 weeks. Endpoints included safety (primary) and RA disease activity assessments based on American College of Rheumatology (ACR) response, and changes in 28-joint disease activity score-CRP, individual ACR components, as well as soluble bone turnover markers.
  
  
  RESULTS
  CCX354-C was generally well tolerated by study subjects. The ACR20 response at week 12 was 39% in the placebo group, 43% in the 100 mg twice daily group (difference and 95% CI compared with placebo, 4.5 (-14.1 to 23.1); p=0.62) and 52% in the 200 mg once daily group (13.0 (-5.8 to 31.8); p=0.17) in the intention-to-treat population, and 30% in the placebo group, 44% in the 100 mg twice daily group (14.4 (-5.9 to 34.8); p=0.17), and 56% in the 200 mg once daily group (25.8 (5.3 to 46.4); p=0.01) in the prespecified population of patients satisfying CRP and joint count eligibility criteria at the screening and day 1 (predose) visits.
  
  
  CONCLUSIONS
  CCX354-C exhibited a good safety and tolerability profile and evidence of clinical activity in RA.
authors.affiliation: Clinical Immunology and Rheumatology, F4-105, AMC/University of Amsterdam, Amsterdam 1100 DD, The Netherlands. p.p.tak@amc.uva.nl
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.forename: Andra
authors.initials: A
authors.lastname: Balanescu
authors.forename: Vira
authors.initials: V
authors.lastname: Tseluyko
authors.forename: Silvia
authors.initials: S
authors.lastname: Bojin
authors.forename: Edit
authors.initials: E
authors.lastname: Drescher
authors.forename: Dan
authors.initials: D
authors.lastname: Dairaghi
authors.forename: Shichang
authors.initials: S
authors.lastname: Miao
authors.forename: Vittorio
authors.initials: V
authors.lastname: Marchesin
authors.forename: Juan
authors.initials: J
authors.lastname: Jaen
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Schall
authors.forename: Pirow
authors.initials: P
authors.lastname: Bekker
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D054389:Receptors, CCR1 / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; C515300:CCR1 protein, human; D054389:Receptors, CCR1