title: Intra-articular primatised anti-CD4: efficacy in resistant rheumatoid knees. A study of combined arthroscopy, magnetic resonance imaging, and histology.
abstract: OBJECTIVE
  CD4+ T cells sustain the chronic synovial inflammatory response in rheumatoid arthritis (RA). SB-210396/CE 9.1 is an anti-CD4 monoclonal antibody that has documented efficacy in RA when given intravenously. This study aimed to establish the safety and efficacy of the intra-articular administration of SB-210396/CE 9.1 compared with placebo, examining its mode of action using a combined imaging approach of arthroscopy, magnetic resonance imaging (MRI), and histology.
  
  
  METHODS
  Thirteen RA patients with active, resistant knee synovitis, were randomised to intra-articular injection of placebo (n=3), 0.4 mg (n=3) or 40 mg (n=7) of anti-CD4 after sequential dynamic gadolinium enhanced MRI, followed by same day arthroscopy and synovial membrane biopsy. Imaging and arthroscopic synovial membrane sampling were repeated at six weeks. This study used a unique region of interest (ROI) analysis mapping the MRI area analysed to the specific biopsy site identified arthroscopically, thus providing data for all three modalities at the same synovial membrane site.
  
  
  RESULTS
  12 patients completed the study (one placebo treated patient refused further MRI). Arthroscopic improvement was observed in 0 of 2 placebo patients but in 10 of 10 patients receiving active drug (>20% in 6 of 10). Improvement in MRI was consistently observed in all patients of the 40 mg group but not in the other two groups. A reduction in SM CD4+ score was noted in the 40 mg group and in the 0.4 mg group. Strong correlations both before and after treatment, were identified between the three imaging modalities. Intra-articular delivery of SB-210396/CE 9.1 was well tolerated.
  
  
  CONCLUSIONS
  SB-210396/CE 9.1 is safe when administered by intra-articular injection. A trend toward efficacy was found by coordinated MRI, arthroscopic, and histological imaging, not seen in the placebo group. The value of ROI analysis was demonstrated.
authors.affiliation: Rheumatology and Rehabilitation Research Unit, Leeds SmithKline Beecham Pharmaceuticals, Leeds LS3 9NZ, United Kingdom.
authors.forename: D J
authors.initials: DJ
authors.lastname: Veale
authors.forename: R J
authors.initials: RJ
authors.lastname: Reece
authors.forename: W
authors.initials: W
authors.lastname: Parsons
authors.forename: A
authors.initials: A
authors.lastname: Radjenovic
authors.forename: P J
authors.initials: PJ
authors.lastname: O'Connor
authors.forename: C S
authors.initials: CS
authors.lastname: Orgles
authors.forename: E
authors.initials: E
authors.lastname: Berry
authors.forename: J P
authors.initials: JP
authors.lastname: Ridgway
authors.forename: U
authors.initials: U
authors.lastname: Mason
authors.forename: A W
authors.initials: AW
authors.lastname: Boylston
authors.forename: W
authors.initials: W
authors.lastname: Gibbon
authors.forename: P
authors.initials: P
authors.lastname: Emery
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000473:pathology / Q000628:therapy*; D001182:Arthroscopy; D015704:CD4 Antigens / Q000032:analysis / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000276:immunology* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology; D013585:Synovitis / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; C121251:keliximab