- Oral presentation
- Open Access
The use of imaging and biomarkers in the assessment and follow-up of arthritis
Arthritis Res Thervolume 6, Article number: 28 (2004)
The use of imaging allows an accurate definition of the pathogenesis of patients with inflammatory arthritis. It can identify certain predictive prognostic factors, such as erosions or the level of synovitis. By using three-dimensional imaging up to 10-fold greater sensitivity for the assessment of erosions is achieved. Using such methods it is possible to produce a more homogeneous population for entry into studies. The results of this are an improvement in outcome data with a consistency of response.
By directly imaging the site of pathology it is possible to increase both the sensitivity and validity of a study; for example, the level of synovitis can be used as a direct measure of outcome. Measuring erosions using ultrasound or magnetic resonance imaging can increase the sensitivity of studies that have as their endpoint structural damage. By increasing the power of studies it is possible to use smaller numbers of patients. These can be used at the phase I/II level of drug development to establish the probable efficacy/usefulness.
In rheumatic conditions where effective therapies have been demonstrated there is no a major problem with placebo use. This is a particular problem with studies of conventional drugs that require large patient numbers because of the insensitivity of the X-ray end points. Furthermore, it is only possible to show tests between active therapy and placebo rather than between two active therapies. The increased sensitivity and accuracy of the new imaging methods allow comparison between active comparators with the power to show differences with relatively small numbers. This has benefits for patients who are not exposed to placebo, for investigators who can compare current best therapies and new therapies, and for organisers of clinical studies with results produced much more rapidly.
There are number of biological markers that can be used for the assessment and follow-up of arthritis patients. The acute phase C-reactive protein is a very sensitive measure of inflammation and an excellent predictor of radiological damage. In biologic studies there is evidence of its predictive value very early in the follow-up process. There are a number of markers in serum and urine that can be used as surrogates of bone and cartilage damage. Their main use is when the normal predictors of damage are absent when early phase studies preclude the use of long-term follow-up.
Conaghan P, O'Connor P, McGonagle D, Astin P, Wakefield RJ, Gibbon W, Quinn M, Karim Z, Green MJ, Produman S, et al: Arthritis Rheum. 2003, 48: 64-71. 10.1002/art.10747. [Pathogenesis]
Tan AL, Tanner SF, Conaghan PG, Radjenovic A, O'Connor P, Brown AK, Emery P, McGonagle D: Arthritis Rheum. 2003, 48: 1214-1222. 10.1002/art.10963. [Pathogenesis]
Kraan MC, Reece RJ, Smeets TJM, Veale DJ, Emery P, Tak PP: Arthritis Rheum. 2002, 46: 2034-2038. 10.1002/art.10556. [Pathogenesis]
McGonagle D, Conaghan P, O'Connor P, Gibbon W, Green M, Wakefield R, Ridgway J, Emery P: Arthritis Rheum. 1999, 42: 1706-1711. 10.1002/1529-0131(199908)42:8<1706::AID-ANR20>3.0.CO;2-Z. [Pathogenesis]
McGonagle D, Gibbon W, O'Conner P, Green M, Pease C, Ridgeway J, Emery P: Lancet. 1999, 353: 123-124. 10.1016/S0140-6736(05)76160-2. [Pathogenesis]
Reece RJ, Canete JD, Parsons WJ, Emery P, Veale DJ: Arthritis Rheum. 1999, 42: 1481-1484. 10.1002/1529-0131(199907)42:7<1481::AID-ANR23>3.0.CO;2-E.
McGonagle D, Gibbon W, Emery P: The Lancet. 1998, 352: 1137-1140. 10.1016/S0140-6736(97)12004-9. [Pathogenesis]
Wakefield RJ, Brown AK, O'Connor P, Emery P: Arthritis Rheum. 2002, 46: 3168-3177. 10.1002/art.10311. [Validation]
Karim Z, Wakefield RJ, Conaghan P, Lawson C, Goh E, Quinn M, Astin P, O'Connor P, Gibbon W, Emery P: Arthritis Rheum. 2001, 44: 2932-2933. 10.1002/1529-0131(200112)44:12<2932::AID-ART481>3.0.CO;2-3. [Validation]
Wakefield RJ, Gibbon W, Conaghan P, McGonagle D, Pease C, Green MJ, Veale DJ, Isaacs JD, Emery P: Arthritis Rheum. 2000, 43: 2762-2770. 10.1002/1529-0131(200012)43:12<2762::AID-ANR16>3.0.CO;2-#. [Validation]
Reece R, Kraan M, Radjenovic A, Veale D, O'Connor P, Ridgway J, Gordon W, Breeveld F, Tak P, Emery P: Arthritis Rheum. 2002, 46: 366-372. 10.1002/art.10084. [Proof of concept study]
Marzo-Ortega H, McGonagle D, O'Connor P, Emery P: Arthritis Rheum. 2001, 44: 2112-2117. 10.1002/1529-0131(200109)44:9<2112::AID-ART363>3.0.CO;2-H. [Proof of concept study]
Veale DJ, Reece RJ, Parsons W, Radjenovic A, O'Connor P, Orgles CS, Berry E, Ridgway JP, Mason U, Boylston AW, et al: Ann Rheum Dis. 1999, 58: 342-349. [Proof of concept study]