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

Berry Objectives-CD4+ T cells sustain the chronic synovial inflammatory res ponse in rheumatoid arthritis (RA). SB-210396/CE 9.1 is an anti-CD4 monoclo nal antibody that has documented efficacy in RA when given intravenously. T his study aimed to establish the safety and efficacy of the intra-articular administration of SB-210396/CE 9.1 compared with placebo, examining its mo de of action using a combined imaging approach of arthroscopy, magnetic res onance imaging (MRI), and histology. Methods-Thirteen RA patients with active, resistant knee synovitis, were ra ndomised 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, foll owed by same day arthroscopy and synovial membrane biopsy. Imaging and arth roscopic synovial membrane sampling were repeated at six weeks. This study used a unique region of interest (ROI) analysis mapping the MRI area analys ed 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 refuse d further MRI). Arthroscopic improvement was observed in 0 of 2 placebo pat ients but in 10 of 10 patients receiving active drug (>20% in 6 of 10). Imp rovement in MRI Berry was consistently observed in all patients of the 40 m g group but not in the other two groups. A reduction in SM CD4+ score was n oted in the 40 mg group and in the 0.4 mg group. Strong correlations both b efore and after treatment, were identified between the three imaging modali ties. 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 i njection. A trend toward efficacy was found by coordinated MRI, arthroscopi c, and histological imaging, not seen in the placebo group. The value of RO I analysis was demonstrated.