title: CD4 coating, but not CD4 depletion, is a predictor of efficacy with primatized monoclonal anti-CD4 treatment of active rheumatoid arthritis.
abstract: OBJECTIVE
  Double blind studies were conducted with the anti-CD4 monoclonal antibody (Mab) keliximab in patients with active, stable rheumatoid arthritis (RA), to confirm preliminary evidence of efficacy and safety from open. uncontrolled studies.
  
  
  METHODS
  We enrolled 136 and 186 patients into 2 consecutive, randomized, double blind trials, with similar populations [apart from inclusion of disease modifying antirheumatic drug (DMARD)-naïve patients in Study 2]. Patients received 4 weeks intravenous placebo or keliximab [40, 80, 120, or 140 mg twice weekly (bw), or 240 mg once weekly (ow)]. The primary endpoint was the American College of Rheumatology (ACR) 20 response criteria, one week after the end of treatment.
  
  
  RESULTS
  ACR 20 response rates in Study I were 19%, 42%, 51%*, and 69%* (*p < 0.05 compared to placebo), with placebo, 40, 80, or 140 mg keliximab bw, respectively. The response rates in Study 2 were 30%, 39%, 46% and 47% with placebo, 80 or 120 mg bw, or 240 mg keliximab ow, respectively. In the 2 studies, there was a dose dependent increase in peripheral blood CD4+ T cell coating with keliximab, but a different pattern of CD4 depletion was seen. While only 12% of keliximab treated patients in Study I had CD4 counts below 250 cells/mm3 at the end of the treatment period, 47% fell below this level in Study 2. Clinical response was not correlated with CD4 depletion, but was correlated with CD4+ T cell coating with keliximab.
  
  
  CONCLUSIONS
  Coating of peripheral blood CD4+ T cells with keliximab, but not CD4 depletion, is a determinant of clinical response.
authors.affiliation: GlaxoSmithKline Pharmaceuticals, Greenford, Middlesex, UK. Ursula_Mason-1@gsk.com
authors.forename: Ursula
authors.initials: U
authors.lastname: Mason
authors.forename: Jose
authors.initials: J
authors.lastname: Aldrich
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Breedveld
authors.forename: Charles B
authors.initials: CB
authors.lastname: Davis
authors.forename: Michael
authors.initials: M
authors.lastname: Elliott
authors.forename: Mildred
authors.initials: M
authors.lastname: Jackson
authors.forename: Christian
authors.initials: C
authors.lastname: Jorgensen
authors.forename: Edward
authors.initials: E
authors.lastname: Keystone
authors.forename: Robert
authors.initials: R
authors.lastname: Levy
authors.forename: John
authors.initials: J
authors.lastname: Tesser
authors.forename: Mark
authors.initials: M
authors.lastname: Totoritis
authors.forename: Alemseged
authors.initials: A
authors.lastname: Truneh
authors.forename: Michael
authors.initials: M
authors.lastname: Weisman
authors.forename: Craig
authors.initials: C
authors.lastname: Wiesenhutter
authors.forename: David
authors.initials: D
authors.lastname: Yocum
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy*; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D005260:Female; D006304:Health Status; D006801:Humans; D007596:Joints / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015704:CD4 Antigens; C121251:keliximab