Background Magnetic resonance (MR) imaging is widely used to assess the joints of patients with rheumatoid arthritis (RA).
Objectives To evaluate the prevention of knee joint destruction and clinical efficacy of methotrexate (MTX) plus etanercept (ETN) compared with MTX monotherapy in RA using semi-automated software for MR image analysis.
Methods This study enrolled patients aged 20-80 years at time of consent with active moderate to severe RA, based on 1987 ACR criteria and 28-joint Disease Activity Score (DAS28) ≥3.2, who displayed inadequate response to oral MTX (stable dosing 8 mg/week for minimum 3 months) at screening. Patients were only enrolled following demonstration of normal creatinine clearance as administration of contrast was part of the MRI protocol. The study is conducted as open-label. Patients were assigned to receive either MTX plus ETN or MTX monotherapy (10 mg/week and over). The primary endpoint was the quantitative knee cartilage volume using our developed software for MR image analysis [Time Frame: 0, 3, 6, 12 months]. MRI images were obtained on a 3T scanner (Philips Achieva 3T; Philips Electronics). An eight-element SENSE phased array coil was used. In our developed semi-automated software, synovial membrane and cartilage segmentation were determined using an active contour model on each slice of MR image series. Then the software counts the number of pixels contained within each contour, multiplies by the pixel size, and sums the results from all slices. This value represents the volume of synovial membrane and articular cartilage. The cartilage thickness is computed by the distance perpendicular from the bone surface to the cartilage surface using scaled color mapping. The representative image is shown in Figure 1. This study was approved by the appropriate ethical committees. Trial Registration: UMIN Clinical Trials Registry, UMIN000005773.
Results A total of 18 female patients were enrolled in this study and allocated to the MTX plus ETN group (n=9, 52.2 [10.6] years) and the MTX monotherapy group (n=9, 54.4 [13.6] years). There were no significant differences between the groups in terms of pretreatment characteristics or baseline disease activity. At 12 months, quantitative knee cartilage volume was significantly decreased compared with baseline in both groups (MTX plus ETN group 2.3±2.3 cm3, MTX monotherapy group 2.4±1.6 cm3), however, there were no significant differences between the groups. Furthermore, we compared the quantitative knee cartilage volume between groups with (4 patients, MTX plus ETN:n=2, MTX monotherapy:n=2) and without (14 patients) strong synovitis (total enhanced synovial volume at baseline was 30cm3 and over). The knee cartilage loss was significantly higher among patients with strong synovitis (group with strong synovitis: 5.0±2.6cm3, group without strong synovitis: 1.5±0.7 cm3, ANOVA: p=0.0002). Synovial volume was strongly associated with MMP3 (Pearson correlation coefficient 0.791, 95% confidential interval 0.526-0.916).
Conclusions Semi-automated software for MR image analysis can reveal useful and potentially clinically important information on the characteristics of knee joint destruction in rheumatoid arthritis.
Acknowledgements The work was sponsored by, Pfizer, Inc.
Disclosure of Interest H. Oka Grant/research support: Pfizer, Inc., S. Ohashi: None declared, Y. Kadono: None declared, T. Yasui: None declared, K. Ono: None declared, K. Isawa: None declared, N. Yoshimura: None declared, J. Nishino: None declared, S. Tanaka: None declared