Ultrasound of metacarpophalangeal joints is a sensitive and reliable endpoint for drug therapies in rheumatoid arthritis: results of a randomized, two-center placebo-controlled studyReport as inadecuate




Ultrasound of metacarpophalangeal joints is a sensitive and reliable endpoint for drug therapies in rheumatoid arthritis: results of a randomized, two-center placebo-controlled study - Download this document for free, or read online. Document in PDF available to download.

Arthritis Research and Therapy

, 14:R198

First Online: 12 September 2012Received: 23 March 2012Revised: 12 June 2012Accepted: 12 September 2012

Abstract

IntroductionWe aimed to investigate the sensitivity and reliability of two-dimensional ultrasonographic endpoints at the metacarpophalageal joints MCPJs and their potential to provide an early and objective indication of a therapeutic response to treatment intervention in rheumatoid arthritis RA.

MethodsA randomized, double-blind, parallel-group, two-center, placebo-controlled trial investigated the effect on ultrasonographic measures of synovitis of repeat dose oral prednisone, 15mg or 7.5mg, each compared to placebo, in consecutive two-week studies; there were 18 subjects in a 1:1 ratio and 27 subjects in a 2:1 ratio, respectively. All subjects met the 1987 American College of Rheumatology criteria for the diagnosis of RA, were ≥18 years-old with RA disease duration ≥6 months, and had a Disease Activity Score 28 based on C-reactive protein DAS28CRP ≥3.2. Subjects underwent high-frequency gray-scale and power Doppler ultrasonography at Days 1 baseline, 2, 8 and 15 in the dorsal transverse and longitudinal planes of all 10 MCPJs to obtain summated scores of quantitative and semi-quantitative measures of synovial thickness as well as vascularity. The primary endpoint was the summated score of power Doppler area measured quantitatively in all 10 MCPJs in the transverse plane at Day 15. Clinical efficacy was assessed at the same time points by DAS28CRP.

ResultsAll randomized subjects completed the trial. The comparison between daily 15 mg prednisone and placebo at Day 15 yielded a statistically significant treatment effect effect size = 1.17, P = 0.013 in change from baseline in the primary endpoint, but borderline for prednisone 7.5 mg daily versus placebo effect size = 0.61, P = 0.071. A significant treatment effect for DAS28CRP was only observed at Day 15 in the prednisone 15 mg group effect size = 0.95, P = 0.032. However, significant treatment effects at all time points for a variety of ultrasound US endpoints were detected with both prednisone doses; the largest observed effect size = 2.33. Combining US endpoints with DAS28CRP improved the registration of significant treatment effects. The parallel scan inter-reader reliability of summated 10 MCPJ scores were good to excellent ICC values >0.61 for the majority of US measures.

ConclusionsUltrasonography of MCPJs is an early, reliable indicator of therapeutic response in RA with potential to reduce patient numbers and length of trials designed to give preliminary indications of efficacy.

Trial RegistrationClinicaltrials.gov identifier: NCT00746512

AbbreviationsACRAmerican College of Rheumatology

AEadverse event

B and LSt Bartholomew-s and the London National Health System Trust

CASSComputerized Allocation Schedule System

CRPC-reactive protein

DAS28Disease Activity Score in 28 Joints

DMARDsdisease modifying anti-rheumatic drugs

HFUShigh-frequency ultrasonography

ICCintra-class correlation coefficients

KIRKennedy Institute of Rheumatology

MCPJmetacarpophalangeal joint

MRImagnetic resonance imaging

PDPower Doppler

PDAPower Doppler Area

PDUSPower Doppler ultrasonography

ROIregion of interest

STAsynovial thickness area

STisynovial thickness index

VASCivascularity index.

Electronic supplementary materialThe online version of this article doi:10.1186-ar4034 contains supplementary material, which is available to authorized users.

Matthew W Seymour, Stephen Kelly contributed equally to this work.

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