Volume 1 Supplement 1
Assessment of Innovative Therapies: A Mode-of-Action Approach
- Paul Emery1
© Current Science Ltd 2000
Published: 15 November 1999
A better understanding of the pathogenesis of rheumatoid arthritis (RA) has led to a number of new therapeutic possibilities. The clinical introduction of such novel pharmaceutical molecules is usually delayed because of difficulty in assessing their in vivo potential. Furthermore there is considerable wastage in early development as phase I and II studies do not formally assess true disease modification, concentrating instead on symptomatic efficacy and toxicity. The availability of targeted therapies, such as blockade of TNF, highlight the inadequacy of such an approach.
The rapid advances in imaging techniques have revolutionised the possibilities for drug development. The modalities include small needle arthroscopy with synovial biopsy, dynamic enhanced high-field magnetic resonance imaging (MRI), fan-beam dual energy X-ray absorptionometry (DXA) and high resolution ultrasound (HRUS). Instead of large numbers of patients being studied using insensitive end points, proof of concept/mode of action studies undertake intensive investigation of highly selected patients, using predetermined end points usually involving the primary target organ.
Multidimentional imaging studies have been undertaken to directly examine novel therapies, which include intra-articular anti-CD4, combination monoclonal antibodies, stem-cell transplantation, and comparisons of novel pharmaceutical agents, eg, the direct effect of corticosteroids on the synovium. These studies, which are scored in a blinded fashion, have shown significant changes in small numbers of patients. Depending on the type of disease, the imaging can focus on either the synovium (knee) or the synovial/bone interface (hand). The value of individual techniques will be discussed and a developmental plan for therapies in arthritic disease proposed.
- Veale DJ, Reece RJ, Parsons W, et al: Intra-articular primatised anti-CD4: efficacy in resistant rheumatoid knees. A study of combined arthroscopy, magnetic resonance imaging, and histology. Ann Rheum Dis. 1999, 58: 342-349.PubMedPubMed CentralView ArticleGoogle Scholar
- IA Corticosteroids prevent progression of erosions in MTX treated early RA-An MRI/HRUS study. Arthritis Rheum. 1998, 41(suppl): S238-Google Scholar