title: A phase II, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of MDX-1100, a fully human anti-CXCL10 monoclonal antibody, in combination with methotrexate in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  CXCL10 (also known as interferon-γ-inducible 10-kd protein [IP-10]) is a chemokine that potentially plays a role in the immunopathogenesis of rheumatoid arthritis (RA). We undertook this phase II study to evaluate the efficacy and safety of MDX-1100, a fully human, anti-CXCL10 (anti-IP-10) monoclonal antibody, in RA patients whose disease responded inadequately to methotrexate (MTX).
  
  
  METHODS
  Patients with active RA receiving stable doses of MTX (10-25 mg weekly) were randomized to receive intravenous doses of 10 mg/kg MDX-1100 (n = 35) or placebo (n = 35) every other week. The primary end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) on day 85, and patients were followed up for safety to day 141.
  
  
  RESULTS
  The ACR20 response rate was significantly higher among MDX-1100-treated patients than among placebo-treated patients (54% versus 17%; P = 0.0024). Statistically significant differences in the ACR20 response rate between treatments were observed starting on day 43 (P < 0.05). The ACR50 and ACR70 response rates on day 85 did not differ between the groups. Overall, 51.4% of MDX-1100-treated patients and 30.3% of placebo-treated patients experienced at least 1 adverse event (AE). No study drug-related serious AEs were reported.
  
  
  CONCLUSIONS
  MDX-1100 was well tolerated and demonstrated clinical efficacy in RA patients whose disease responded inadequately to MTX. This is the first study to demonstrate clinical efficacy of a chemokine inhibitor in RA and supports the notion of a potential role of IP-10 in the immunopathogenesis of RA.
authors.affiliation: Medarex, Bloomsbury, NJ, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Yellin
authors.forename: Igor
authors.initials: I
authors.lastname: Paliienko
authors.forename: Andra
authors.initials: A
authors.lastname: Balanescu
authors.forename: Semen
authors.initials: S
authors.lastname: Ter-Vartanian
authors.forename: Vira
authors.initials: V
authors.lastname: Tseluyko
authors.forename: Li-An
authors.initials: LA
authors.lastname: Xu
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Tao
authors.forename: Pina M
authors.initials: PM
authors.lastname: Cardarelli
authors.forename: Heidi
authors.initials: H
authors.lastname: Leblanc
authors.forename: Geoff
authors.initials: G
authors.lastname: Nichol
authors.forename: Codrina
authors.initials: C
authors.lastname: Ancuta
authors.forename: Rodica
authors.initials: R
authors.lastname: Chirieac
authors.forename: Allison
authors.initials: A
authors.lastname: Luo
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D054357:Chemokine CXCL10 / Q000037:antagonists & inhibitors*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D054357:Chemokine CXCL10; C574193:MDX-1100; D008727:Methotrexate