Erosive progression is arrested in rheumatoid arthritis patients who are treated with adalimumab and methotrexate combination therapy, judging from results of a novel longitudinal study comparing MRI, ultrasonography, CT, and radiography.
However, only MRI was sensitive enough to document repair of individual erosions. Both MRI and ultrasound could detect changes in bone edema, which "was predictive of subsequent erosive progression on CT, both at the individual bone/joint level and also for MRI bone edema at the patient level," reported lead author Dr. Uffe Møller Døhn of the department of rheumatology at the University of Copenhagen in the February 2011 edition of the Annals of the Rheumatic Diseases. "These data emphasize the predictive value of modern imaging, and especially highlight the importance of MRI bone edema for predicting erosive progression."
The findings also offer a different way of thinking about RA’s pathology. In an accompanying editorial, Dr. Fiona McQueen and Dr. Esperanza Naredo said that the study’s findings add to existing evidence suggesting that osteitis is more strongly predictive of bone erosion than is synovitis, which supports "the notion that there is a more direct connection between bone inflammation and bone damage than between synovial inflammation and bone damage" (Ann. Rheum. Dis. 2011;70:241-4). They described synovitis and osteitis as "cousins with a common ancestor, the process that ultimately drives both remaining obscure but possibly sited in the bone marrow."
Dr. Døhn and his associates used MRI, ultrasound, standard radiography, and high-resolution CT images of the wrist and metacarpophalangeal joints 2-5 to study response to adalimumab/methotrexate therapy in 52 RA patients naive to biological agents. All images were obtained before the first dose of adalimumab injection and were repeated after 6 and 12 months of treatment (Ann. Rheum. Dis. 2011;70:252-8).
The median age of patients was 61 years, and 67% were women. From baseline, the researchers did not observe any statistically significant changes in overall bone destruction or repair at 6 or 12 months, but differences were seen when researchers used the smallest-detectable-change cutoff. For example, after 6 and 12 months, the scores of MRI synovitis, grey-scale synovitis, and power Doppler ultrasonography decreased. So did scores as assessed by DAS28 (disease activity score in 28 joints), a health assessment questionnaire, and tender and swollen joint counts.
Study participants with disease progression on CT had higher baseline MRI bone edema scores. In fact, when baseline MRI bone edema was present, the risk ratio for erosive progression in the same bone on CT at 12 months was 3.8. In addition, time-integrated MRI bone edema, power Doppler, and grey-scale synovitis scores were higher in bones and joints with CT progression.
With CT as the reference method, the researchers determined that the sensitivity and specificity for the other imaging modalities were 68% and 92%, respectively, on MRI; 44% and 95% on ultrasonography; and 26% and 98% on radiography.
In their concluding remarks in the editorial, Dr. McQueen and Dr. Naredo emphasized that the reduction of both synovitis and osteitis "is clearly an important therapeutic goal" in treating RA. "The detection and monitoring of synovitis is often more feasible in clinical practice using [ultrasound] than MRI scanning, but the latter does afford the opportunity to detect and monitor bone edema at the same time."
Dr. McQueen is with the department of molecular medicine and pathology at the University of Auckland (New Zealand). Dr. Naredo is with the department of rheumatology at the Hospital Universitario Severo Ochoa in Madrid.
Funding for the study was provided by Abbott Denmark, the Danish Rheumatism Association, and the Aase and Ejner Danielsen Foundation. Dr. Døhn reported no relevant financial conflicts, but many of the study’s coauthors disclosed that they have received consulting fees, speaking fees, or research grants from Abbott, Centocor, Roche, Schering-Plough, UCB-Nordic, and Wyeth. Dr. McQueen and Dr. Naredo stated that they have no conflicts of interest.