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Ann Rheum Dis 1999;58:342-349 doi:10.1136/ard.58.6.342
  • Extended reports

Intra-articular primatised anti-CD4: efficacy in resistant rheumatoid knees. A study of combined arthroscopy, magnetic resonance imaging, and histology

  1. D J Vealea,
  2. R J Reecea,
  3. W Parsonsa,
  4. A Radjenovicb,
  5. P J O’Connorb,
  6. C S Orglesb,
  7. E Berryb,
  8. J P Ridgwayb,
  9. U Masond,
  10. A W Boylstonc,
  11. W Gibbonb,
  12. P Emerya
  1. aRheumatology and Rehabilitation Research Unit, bCentre of Medical Imaging Research, cand Department of Molecular Medicine, dUniversity of Leeds, Leeds SmithKline Beecham Pharmaceuticals
  1. Professor P Emery, 36 Clarendon Road, Leeds LS3 9NZ.
  • Accepted 10 February 1999

Abstract

OBJECTIVES 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.

Footnotes

  • Funding: this work was supported by SmithKline Beecham Pharmaceuticals, New Frontiers Science Park (South), Third Avenue, Harlow, Essex, CM19 5AW, United Kingdom.

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