Magnetic resonance imaging (MRI) studies of rheumatoid arthritis (RA) patients treated with rituximab (RTX, Rituxan®) after the failure of TNF-inhibitor therapy confirm that the B-cell depleting agent stopped disease progression for at least 1 year, and suggest that some healing of joint damage occurred
Results were reported at the 2008 EULAR meeting by Uffe Møller Døhn, MD, and colleagues from Copenhagen University Hospitals in Denmark, the University of New South Wales in Australia, and Netherlands University Hospital, Maastricht in The Netherlands.1
The study included 10 women with active RA and median disease duration of 8 years. These patients had a mean of five previous DMARDs, including anti-TNFα therapies.
The investigators assessed high resolution (voxel size 0.4x0.4x0.4 mm) contrast enhanced MRI of dominant wrist and metacarpophalangeal joints 2-5 and radiographs of both hands and forefeet at baseline and after 6 and 12 months. The MRI images were scored for erosions, synovitis and bone edema according to the OMERACT-RAMRIS criteria. Radiographs were scored according to the Sharp/van der Heijde (S/vdH) method. The researchers assessed DAS28-CRP and health assessment questionnaire (HAQ) scores at all visits. Secondary endpoints were signs of radiographic progression and signs of clinical disease activity.?
The median baseline DAS28 was 5, baseline tender joint count 7, and baseline swollen joint count 8; baseline HAQ was 1.625. Baseline mean MRI scores were as follows: bone erosions 31, synovitis 7, and bone edema 8; baseline total S/vdH score was 84.
At both 6 and 12 months, RTX was associated with significant decreases in DAS28 (P <.001). At 6 months, 10% of RTX-treated patients achieved ACR70 response, 10% achieved ACR50, and 40% achieved ACR20. Dr. Møller Døhn said that 60% of patients reached EULAR good or moderate responses at 6 months. ?By 12 months, ACR70 response rate increased to 13%, ACR50 increased to 25%, and ACR20 to 50%. Sixty-three percent of patients reached EULAR good or moderate response. Also at 12 months, mean MRI bone erosions score dropped by -0.5 points, MRI synovitis score dropped by -2.6, and mean bone edema score dropped by -0.6.
“A significant reduction in MRI synovitis score was observed after 1 year (P <.05), but not at 6 months,” Dr. Møller Døhn said. The changes in MRI scores of erosions and bone edema at 12 months or in any radiographic score at 6 or 12 months were not statistically significant. “RA patients treated with RTX showed no mean progression on MRI and radiography after 1 year, rather there was overall a small tendency towards erosive regression. A significant reduction in MRI synovitis was seen at 1 year. Larger studies are needed to confirm these findings, and to establish if MRI findings have a predictive value with respect to radiographic and clinical outcome in RA patients treated with RTX.”
Translating research into practice
The study adds to questions now being raised about the practice of switching RA patients to a second TNF-inhibitor if a first does not provide adequate disease control. Changing to RTX may be a more effective strategy.
Related studies by Cohen et al, also reported at EULAR, showed that RTX treatment over 2 years significantly reduced changes in the Total Sharp Score and essentially stopped disease progression in patients who had inadequate response to TNF inhibition.2
References
1. Møller Døhn U, Bird P, Østergaard M, et al. Rheumatoid arthritis (RA) patients treated with rituximab showed no mean erosive progression, but a small tendency towards regression, on magnetic resonance imaging (MRI) and conventional radiography 1 year after treatment. Presented at: EULAR 2008; June 11-14, 2008; Paris, France. Presentation OP-0185.
2. Cohen S, Keystone E, Genovese MC, et al. Continued inhibition of structural damage in rheumatoid arthritis patients treated with rituximab at 2 years: REFLEX study. Presented at: EULAR 2008; June 11-14, 2008; Paris, France. Presentation THU-0167.
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