Rheumatoid Arthritis: Gibbon W

Conaghan P, Edmonds J, Emery P, Genant H, Gibbon W, Klarlund M, Lassere M, McGonagle D, McQueen F, O'Connor P, Peterfy C, Shnier R, Stewart N, Ostergaard M. · Rheumatology Research Unit, University of Leeds, UK. · J Rheumatol. · Pubmed #11361206 No free full text.

Abstract: Complementing the 3 papers that precede it, this paper explains the rationale for the activities of an OMERACT working party on magnetic resonance imaging (MRI) evaluation of rheumatoid arthritis (RA), sets out provisional recommendations for the acquisition and scoring of MRI of the hand and wrist in RA, and delineates some of the many residual problems that need to be addressed.

McGonagle D, Pease C, Marzo-Ortega H, O'Connor P, Gibbon W, Emery P. · Rheumatology Department, University of Leeds, United Kingdom. · J Rheumatol. · Pubmed #11508586 No free full text.

Abstract: OBJECTIVE: Joint inflammation in polymyalgia rheumatica is regarded primarily as a disease of the synovial cavities and bursae, but the adjacent capsules and soft tissues have not been evaluated using sensitive imaging methods. We used fat suppression magnetic resonance imaging (MRI) to determine anatomical sites of inflammatory change in the shoulders of patients with early polymyalgia rheumatica (PMR) and a control group of patients with rheumatoid arthritis (RA). METHODS: Fourteen patients with PMR and 14 with RA (a total of 20 shoulders in each group) were evaluated. T2 SPIR (fat suppressed) coronal oblique MRI sequences of the shoulders were performed. Scans were assessed for sites of joint effusion, bursitis, tenosynovitis, bone edema, and extracapsular soft tissue edema. Statistical analysis was performed using Fisher's test. RESULTS: Nine of 14 patients (10/20 joints) with PMR but only 2/14 (2/20 joints) with RA had prominent edema at extracapsular sites adjacent to the joint capsule or in the soft tissues (p = 0.02). Both groups had a comparable degree of joint effusion (18 PMR, 17 RA), bursitis (18 PMR, 16 RA), and tenosynovitis (3 PMR, 2 RA). CONCLUSION: The only significant difference between the 2 groups was the presence of inflammatory change outside the joint cavity in patients with PMR. This may contribute to the diffuse nature of symptoms in PMR and have implications for its pathogenesis.

Mc Gonagle D, Gibbon W, O'Connor P, Blythe D, Wakefield R, Green M, Veale D, Emery P. · The Rheumatology Research Unit, University of Leeds, UK. · Rheumatology (Oxford). · Pubmed #10378710 links to  free full text

Abstract: OBJECTIVE: To develop a new technique to assess the primary lesion in early rheumatoid arthritis (RA). METHODS: Ten patients with early RA and radiographically or MRI confirmed erosions had a needle introduced into the base of the erosion under sonographic guidance. Material was then aspirated from this site. RESULTS: The procedure was well tolerated with no complications. Small samples of necrotic bone and tissue were obtained in five out of 10 cases. In one case, a distinctive population of pleomorphic CD34 + cells with characteristics of bone marrow progenitors was isolated. Tissue invading bone with a characteristic appearance of pannus was not seen. CONCLUSION: A new method of sampling the earliest lesion in RA is described. The findings raise questions about the nature of bone damage in early RA.

Veale DJ, Reece RJ, Parsons W, Radjenovic A, O'Connor PJ, Orgles CS, Berry E, Ridgway JP, Mason U, Boylston AW, Gibbon W, Emery P. · Rheumatology and Rehabilitation Research Unit, Leeds SmithKline Beecham Pharmaceuticals, Leeds LS3 9NZ, United Kingdom. · Ann Rheum Dis. · Pubmed #10340958 links to  free full text

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.

McGonagle D, Reade S, Marzo-Ortega H, Gibbon W, O'Connor P, Morgan A, Melsom R, Morgan E, Emery P. · Rheumatology and Rehabilitation Research Unit, University of Leeds, 36 Clarendon Road, Leeds LS2 9NZ, UK. · Ann Rheum Dis. · Pubmed #11406526 links to  free full text

Abstract: The pathogenesis of human immunodeficiency virus (HIV) associated spondyloarthropathy (SpA) is poorly understood. In this case report a patient is described with severe HIV associated reactive arthritis, who on magnetic resonance imaging and sonographic imaging of inflamed knees had extensive polyenthesitis and adjacent osteitis. The arthritis deteriorated despite conventional antirheumatic treatment, but improved dramatically after highly active antiretroviral treatment, which was accompanied by a significant rise in CD4 T lymphocyte counts. The implications of the localisation of pathology and effect of treatment for pathogenic models of SpA and rheumatoid arthritis in the setting of HIV infection are discussed.

McGonagle D, Conaghan PG, O'Connor P, Gibbon W, Green M, Wakefield R, Ridgway J, Emery P. · University of Leeds, UK. · Arthritis Rheum. · Pubmed #10446871 links to  free full text

Abstract: OBJECTIVE: The interrelationship between synovitis and bone damage in rheumatoid arthritis (RA) is a subject of controversy. Using magnetic resonance imaging (MRI), this study followed the bone changes in early RA and determined their relationship to synovitis. METHODS: Thirty-one patients with early RA who had swelling of the metacarpophalangeal (MCP) joints and 31 healthy control subjects with no clinical evidence of arthritis underwent MRI of the second through fifth MCP joints of the dominant hand by use of a 1.5T scanner. Coronal T1-weighted and T2-fat suppressed (FS) sequences were performed to evaluate bone edema, and gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) pulse sequences were obtained to evaluate synovitis. Bony abnormalities were described as bone edema (low signal on T1-weighted sequences and intermediate/high signal on T2 FS sequences adjacent to the bone cortex) or as bone cysts (circular juxtacortical abnormalities with low signal on T1-weighted images and with very high signal on T2 FS sequences). Contrast and noncontrast MRI films were scored in a blinded manner, and Fisher's exact probability test was used to determine differences between groups. RESULTS: Twenty-one of the 31 RA patients (68%) had bone edema, which was seen in 43 of 124 joints (35% of joints) and 3 of the 31 control subjects had bone edema seen in 3 of 124 joints (2% of joints) (P < 0.0001). Thirty RA patients (97%) had Gd-DTPA-confirmed MCP joint synovitis, and bone edema was seen in 40 of the 75 joints with Gd-DTPA-proven synovitis (53%), but in only 3 of 49 without (6%) (P < 0.0001). CONCLUSION: MCP joint bone edema is present in the majority of patients with RA at presentation, but is seen only occasionally in normal control subjects. The fact that bone edema occurred rarely in the absence of synovitis in patients with RA suggests that bony changes in RA are secondary to synovitis.

McGonagle D, Gibbon W, O'Connor P, Green M, Pease C, Ridgway J, Emery P. · No affiliation provided · Lancet. · Pubmed #10023907 No free full text.

This publication has no abstract.