Elsevier

Joint Bone Spine

Volume 72, Issue 6, December 2005, Pages 557-561
Joint Bone Spine

Original article
Magnetic resonance imaging quantification of hand synovitis in patients with rheumatoid arthritis treated with infliximab

https://doi.org/10.1016/j.jbspin.2004.08.014Get rights and content

Abstract

Aim. – To investigate the clinical response and to evaluate by magnetic resonance imaging the inflammatory tissue changes in refractory rheumatoid arthritis patients treated with infliximab.

Methods. – Sixteen refractory rheumatoid arthritis patients who were treated with intravenous infliximab (3 mg/kg) at weeks 0, 2, 6 and every 8 weeks thereafter were examined with magnetic resonance imaging of the dominant affected wrist and hand before treatment and 1 year after therapy. The volume of the enhancing inflammatory tissue was evaluated in fat suppressed contrast enhanced T1-weighted images by using the Analyse 4.0 software. Disease activity was evaluated by assessing the disease activity score for 28 joint indices. The clinical improvement was evaluated according to the American College of Rheumatology 20% response criteria.

Results. – There were 13 females and 3 males with mean age 49.5 (17.0) years and mean disease duration 10.5 (8.0) years. Ten patients had positive IgM rheumatoid factor. One year after treatment, a significant reduction of the erythrocyte sedimentation rate, the C-reactive protein, the disease activity score for 28 joint indices and the volume of the enhancing inflammatory tissue was observed. All but two of the rheumatoid arthritis patients achieved the American College of Rheumatology 20% response criteria, while 9 (56.25%) and 5 (31.25%) patients achieved the 50% and 70% American College of Rheumatology response criteria, respectively. A positive correlation among the volume of the enhancing inflammatory tissue, swollen joint count, tender joint count, as well as disease activity score for 28 joint indices (r = 0.66, r = 0.79, r = 0.57 respectively) was found before treatment.

Conclusions. – In refractory rheumatoid arthritis patients, the addition of infliximab therapy may result in clinical, laboratory and magnetic resonance imaging improvement. Magnetic resonance imaging assessment of the volume of the enhancing inflammatory tissue may represent an additional tool for the investigation of joint disease activity and responsiveness to treatment.

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory disease with prominent joint manifestations. Joint involvement starts with synovial hyperplasia that progresses to synovitis and pannus formation, a highly cellular inflammatory tissue [1], [2]. Pannus erodes cartilage and bone leading to articular destruction and ankylosis [1], [2]. Articular involvement of the hand and wrist is the presenting site in approximately 70% of the patients with RA and frequently reflects the patient's overall disease condition [3], [4]. Conventional radiograms of the hand and wrist have been widely used in the diagnostic work up and follow-up of patients with RA [5]. However, conventional radiograms can only evaluate joint space changes, osteoporosis and erosive lesions [6]. The ultrasound, though it depicts synovium—and when coupled to color Doppler, assesses tissue vascularity—it evaluates superficial structures and image acquisition is operator dependent [7], [8]. Magnetic resonance (MR) imaging evaluates bone lesions (oedema, cysts and erosions), depicts inflammatory synovium in joints and tendon sheaths and distinguishes between active inflammatory and chronic fibrotic synovial tissue [7]. A grading system and/or volume estimation methods used for the evaluation of synovial membrane hypertrophy have been found to be useful for the evaluation of disease activity and response to treatment [9], [10], [11]. Anti-tumor necrosis factor-alpha (TNF-alpha), namely infliximab, is a chimeric monoclonal antibody that inhibits the proinflammatory cytokine TNF-alpha [12]. Moreover, anti-TNF-alpha reduces synovial membrane neo vascularization by decreasing the circulating levels of cytokine vascular endothelial growth factor, which is a major angiogenetic factor [12]. Response to treatment with infliximab has been evaluated by clinical and laboratory assessment as well as by serial radiographs [12]. There are few studies that have used MR imaging for the evaluation of response to infliximab therapy in RA patients [13], [14].

The purpose of the study was to investigate, in patients with refractory RA, the response to infliximab therapy by assessing with MR imaging changes in the volume of the active inflammatory tissue (VEIT) in the dominant hand and wrist.

Section snippets

Methods

Sixteen patients with RA according to the American College of Rheumatology (ACR) criteria were enrolled in the study [15]. There were 13 female and 3 males aged from 21–73 years, mean age 49.5 (17.0) years. The average disease duration was 10.5 (8.0) years (range 2–29 years) at the beginning of the study. Of the 16 patients, 10 were positive for IgM rheumatoid factor (RF). The patients were refractory or did not tolerate at least two disease modifying antirheumatic drugs (DMARDs). The current

Results

After 1 year of treatment, a significant reduction of the ESR, CRP, DAS-28 and VEIT was noted (Table 1). Moreover, all patients but two achieved the 20% ACR response criteria, while 9 (56.25%) and 5 (31.25%) patients achieved the 50% and 70% ACR response criteria, respectively. The two patients who after treatment did not achieve 20% ACR response criteria, on MR imaging follow up showed some increase instead of decrease of VEIT.

Only before treatment, the volume of the enhancing inflammatory

Discussion

TNF-alpha is a potent proinflammatory cytokine, which has been found in significant amounts in the synovial tissue and synovial fluid. TNF-alpha plays a critical role in the progression of synovitis and articular matrix degradation in RA patients [19]. Infliximab, a TNF-alpha inhibitor, has emerged as a key treatment for RA and other rheumatic diseases [20], [21], [22], [23], [24]. Results from several well-designed, controlled clinical trials using infliximab therapy with concomitant use of

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