Infliximab for the Treatment of Early Rheumatoid Arthritis

The current 'gold standard' of measuring osseous damage in patients with RA in the context of clinical trials is the radiographic evaluation of hands and feet. However, conventional radiographs are insensitive to change and extended trial duration is required to reliably document differences of this important surrogate endpoint in the different treatment arms. In this active treatment controlled double blind trial in patients with erosive RA we want to test whether a very sensitive imaging modality, MR images of a typically involved joint, the wrist, can detect differences in the formation of erosions in the two treatment arms with fewer numbers of patients at 6 months. We plan to enroll a total of 60 patients into the study, allocating 20 into methotrexate/placebo arm and 40 into a methotrexate/infliximab arm. The anti-TNF-alpha monoclonal antibody infliximab in combination with methotrexate has been shown to retard the development of bone erosions on conventional radiographs in patients with established rheumatoid arthritis (RA) at one year. We are proposing to use MRI of the most severely involved wrist as a highly sensitive imaging modality to assess differences in the development of new erosions significantly earlier, at 3 and 6 months (primary endpoint) in the two treatment arms. After 6 months, all patients will receive open label treatment of methotrexate in combination with infliximab for an additional 6 months followed by a one year evaluation. We will use MRI again to assess if abnormalities at 6 months are still present at 12 months. Concomitantly we will evaluate the use of bone and cartilage markers as well as endocrine and metabolic markers before and after treatment with infliximab.