Abstract

Given the limitations of clinical composite measures to quantify disease activity in rheumatoid arthritis (RA) and limitations of standard x-rays in quantifying structural joint damage, it is important to consider imaging biomarkers that may provide a more complete and more objective portrayal of the disease process. Objective tools may be more sensitive to change and may more easily discriminate between ineffective and effective therapies. The conduct of clinical trials in RA is highly costly, partly due to the large sample sizes necessary to discriminate effective therapies compared to improving standards of care. Methodologies that can quantify the inflammatory disease burden accurately and with greater sensitivity to change have the potential to reduce sample sizes and study duration and to improve our understanding of the biologic effects of new therapies. A number of trial designs have now incorporated MRI and demonstrated that MRI measures 1) correlate with component indices of clinical disease activity, 2) can accurately assess changes in inflammatory disease burden and structural damage progression related to treatment effects, 3) can predict later radiographic outcomes, and 4) could improve discrimination of effective therapies and reduce sample sizes. There is therefore substantial evidence that MRI would be a reliable as a clinical trial endpoint and would substantially improve study power and reduce required sample sizes and thereby cost. Remaining questions are how to combine MRI with other disease assessments and whether this modality adequately reflects the patient experience to be used as a primary clinical trial endpoint.