Development of a feasible and responsive ultrasound inflammation score for rheumatoid arthritis through a data-driven approach

Abstract

Objective: To develop and validate a responsive and feasible ultrasound inflammation score for rheumatoid arthritis (RA).

Methods: We used data from cohorts of early RA (development) and established RA starting/switching biologic therapy (validation). 4 tendons and 36 joints were examined by a grey scale (GSUS) and power Doppler semiquantitative ultrasound (PDUS) scoring system (full score). Ultrasound score components were selected based on factor analyses of 3-month change in the development cohort. Responsiveness was assessed by standardised response means (SRMs). We assessed the proportion of information retained from the full score by linear regression.

Results: 118 patients with early and 212 patients with established RA were included. The final ultrasound score included 8 joints (metacarpophalangeal 1-2-3, proximal interphalangeal 2-3, radiocarpal, metatarsophalangeal 2-3) and 1 tendon (extensor carpi ulnaris) examined bilaterally. The 6-month SRMs for the final score were -1.24 (95% CI -1.47 to -1.02) for GSUS, and -1.09 (-1.25 to -0.92) for PDUS in early RA, with 87% of total information retained for GSUS and 90% for PDUS. The new score performed somewhat better than formerly proposed scores in the validation cohort.

Conclusions: The Ultrasound in Rheumatoid Arthritis 9 joint/tendon score (USRA9) inflammation score showed good responsiveness, retained most of the information from the original full score and overall performed better than previous scores in a validation cohort.

Trial registration numbers: NCT01205854, ACTRN12610000284066; Post-results.

Keywords: Inflammation; Rheumatoid Arthritis; Ultrasonography.

Conflict of interest statement

All authors have completed the Unified Competing Interest form at http://www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: EAH has received research funding from Pfizer, UCB, Roche, MSD and AbbVie for the submitted work, honoraria as a speaker from Pfizer, UCB, Roche, and AbbVie, honoraria for development of educational material from Pfizer, and has been on advisory board for Pfizer that might have an interest on the submitted work in the previous 3 years. A-BA has been on advisory boards for UCB, AbbVie and Pfizer, and received honoraria for development of educational material for UCB. HBH has received honoraria as a speaker from AbbVie, Bristol-Myers Squibb, Roche, UCB Pharma and Pfizer. HH has been on advisory boards for UCB and AbbVie. GB has received honoraria as a speaker from AbbVie and has been on advisory board for Pfizer. DvdH has received consultancy honoraria from AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Celgene, Daiichi, Eli Lilly, Galapagos, Merck, Novartis, Pfizer, Roche, Sanofi Aventis, Janssen and UCB, and is owner of Imaging Rheumatology. TKK has received consultancy honoraria from AbbVie, Bristol-Myers Squibb, Celltrion, Epirus, Hospira, Merck-Serono, MSD, Orion Pharma, Pfizer and UCB that might have an interest on the submitted work in the previous 3 years.

Figures

Figure 1

The final ultrasound inflammation score (USRA9) for rheumatoid arthritis. (Included joints/tendon: MCP1, MCP2, MCP3, PIP2, PIP3, radiocarpal joint, ECU tendon, MTP2 and MTP3. All joints included in the USRA9 score are examined with a longitudinal scan on the dorsal side. The extensor carpi ulnaris tendon is examined in a longitudinal and transverse scan. All joints and the tendon are scored 0–3 for GSUS (range 0–54) and PDUS (range 0–54). Not included in the USRA9 (elbow and knee were not included and are not shown). ECU, extensor carpi ulnaris; GSUS, grey-scale ultrasound; MCP, metacarpophalangeal; MTP, metatarsophalangeal; PDUS, power Doppler ultrasound; PIP, proximal interphalangeal; USRA9, Ultrasound in Rheumatoid Arthritis 9 joint/tendon score.

Figure 2

SRMs at 3 and 6 months for the final ultrasound inflammation score (USRA9) bilaterally and previously proposed scores (A) GSUS in the early RA cohort, (B) PDUS in the early RA cohort, (C) GSUS in the established RA cohort and (D) PDUS in the established RA cohort. *SRMs (standardised response means); mean change divided by the SD of the change with 95% CIs. †Six-joint score Perricone et al: wrist, MCP2, knee bilaterally. ‡Seven-joint score Backhaus et al: wrist, MCP2, MCP3, PIP2, PIP3, MTP2, MTP5 and extensor carpi ulnaris tendon dominant side. $Twelve-joint score Naredo et al: elbow, wrist, MCP2, MCP3, knee, ankle and tibialis posterior tendon bilaterally. Final ultrasound inflammation score (USRA9): radiocarpal joint, extensor carpi ulnaris tendon, MCP1, MCP2, MCP3, PIP2, PIP3, MTP2, MTP3. Dotted line indicating SRM value of most responsive score. GSUS, grey-scale ultrasound; MCP, metacarpophalangeal; MTP, metatarsophalangeal; PDUS, power Doppler ultrasound; PIP, proximal interphalangeal; RA, rheumatoid arthritis; USRA9, Ultrasound in Rheumatoid Arthritis 9 joint/tendon score.