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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.

Qualitative differences in synovitis between the cartilage-pannus junction (CPJ) region and the adjoining suprapatellar pouch (SPP) have been reported in rheumatoid arthritis and the spondyloarthropathies.To determine if the distribution of synovitis is the same in osteoarthritis (OA) using sensitive measures of inflammation derived from dynamic, contrast enhanced magnetic resonance imaging (DEMRI).20 subjects with established OA of the knee were recruited. Conventional MR images together with the DEMRI measurements were obtained. Areas of synovitis at the CPJ region and at a distant site in the SPP were calculated; differences in CPJ and SPP synovitis were determined using DEMRI parameters: the initial rate of contrast enhancement (IRE) and maximal enhancement (ME).The area of synovitis was significantly greater adjacent to the CPJ than in the SPP. IRE and ME measures were greater at the CPJ than the SPP.The magnitude of synovitis at the CPJ is not disease-specific and applies across the spectrum of degenerative disease as well as inflammatory diseases.

Background We noted in mouse models of inflammatory arthritis (IA) that an early point of entry of inflammation into the marrow space occurs at sites where penetrating vessels entered the bone. The role of penetrating vessels in erosion formation in man has not been explored in IA, nor has the role of vascular channels in bone oedema in osteoarthritis (OA) been explored. Objectives The purpose of this work was to investigate the frequency of bone erosion and oedema in inflammatory and degenerative arthropathies in close proximity to the peri-entheseal ACL and PCL vascular channels. Methods Normal microanatomy was defined in 21 cadaveric knees using 3T MRI and histology. MRI of 89 patients from the Osteoarthritis Initiative study and 27 patients with inflammatory arthritis were evaluated for erosion and bone oedema at the same locations. Two animal models of inflammatory arthritis were evaluated to ascertain whether the putative peri-entheseal vascular regions influenced the propensity of osteitis and bone erosion. Results Data from the two animal models of IA showed inflammation entering the marrow space along the adventitia of blood vessels that penetrate the cortical bone in close proximity to the cruciate ligament insertions. On 3T MRI, a vascular channel adjacent to the ACL tibial insertion was observed in 64% of cadaveric specimens examined. Similarly, a vascular channel adjacent to the PCL was seen in 71% of cases. Bone marrow oedema was observed in the regions corresponding to the location of the vascular channel in 51% of knees for both the anterior and posterior channel. Histological evaluation of 10 cadaveric specimens confirmed the location of the vascular channels along with the presence of associated subclinical microdamage including subchondral bone erosion (80% of cases) and micro-cyst formation (50%). Evaluation of patient MRIs showed the prevalence of oedematous features in the same topographic locations in patients with early OA (41% ACL, 59% PCL) and inflammatory arthritis (44% ACL, 33% PCL), (figure 1 ). Image/graph Conclusions Our findings show that the vascular channels adjacent to the anterior and posterior cruciate ligament entheses are common locations for erosion formation and damage in both inflammatory and degenerative arthritis. Furthermore, we have found a significant clustering of subclinical microdamage in these regions in normal cadaveric samples. Therefore, we conclude that peri-entheseal vascular channels are likely to present a common pathogenesis focus for both OA and IA. Disclosure of Interest None Declared