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To test the sensitivity to change of ultrasonographic endpoints in early phase clinical trials in subjects with active rheumatoid arthritis (RA).A double-blind, placebo and comparator controlled, randomised, two-centre study investigated the effect on synovial thickness and vascularity of 28 days repeat daily oral dosing of 60 mg of the inducible nitric oxide synthase inhibitor GW274150 or 7.5 mg prednisolone in RA. Fifty patients with DAS28 scores ≥4.0 were assigned to 3 treatment arms of 17, 19 and 14 (on placebo, GW274150 and prednisolone respectively). Synovial thickness and vascularity of all 10 metacarpophalangeal joints were assessed by ultrasonography using a semi-quantitative scale at baseline (Day 1), Day 15 and Day 28. Vascularity was also measured quantitatively by power Doppler area.At Day 28, the GW274150 group showed a trend towards reduction in synovial thickness compared with placebo, with an adjusted mean decrease of 33% (p=0.072); the prednisolone group decreased significantly by 44% (p=0.011). Similarly, there was a trend to reduced synovial vascularity with GW274150 by 42% compared with placebo (p=0.075); prednisolone resulted in a statistically significant decrease of 55% (p=0.012). There was a 55% decrease in power Doppler area for GW274150, compared with placebo although the result was not statistically significant (p=0.375). Prednisolone 7.5 mg resulted in a highly statistically significant decrease of 95% (p=0.003).This study advocates the use of ultrasonographic measures of metacarpophalangeal joint synovitis as an endpoint for clinical studies assessing therapeutic potential of new compounds in small patient cohorts over 28 days.

Type

Journal article

Journal

Clinical and experimental rheumatology

Publication Date

03/2012

Volume

30

Pages

254 - 261

Addresses

Kennedy Institute of Rheumatology, London, UK. m.seymour@imperial.ac.uk

Keywords

Metacarpophalangeal Joint, Humans, Arthritis, Rheumatoid, Synovitis, Sulfides, Prednisolone, Antirheumatic Agents, Placebos, Enzyme Inhibitors, Ultrasonography, Doppler, Disability Evaluation, Treatment Outcome, Double-Blind Method, Predictive Value of Tests, Time Factors, Adult, Aged, Middle Aged, England, Female, Male, Nitric Oxide Synthase Type II, Serbia