Value of ultrasonography as a marker of early response to abatacept in patients with rheumatoid arthritis and an inadequate response to methotrexate: results from the APPRAISE study

Abstract

Objectives: To study the responsiveness of a combined power Doppler and greyscale ultrasound (PDUS) score for assessing synovitis in biologic-naïve patients with rheumatoid arthritis (RA) starting abatacept plus methotrexate (MTX).

Methods: In this open-label, multicentre, single-arm study, patients with RA (MTX inadequate responders) received intravenous abatacept (∼10 mg/kg) plus MTX for 24 weeks. A composite PDUS synovitis score, developed by the Outcome Measures in Rheumatology-European League Against Rheumatism (OMERACT-EULAR)-Ultrasound Task Force, was used to evaluate individual joints. The maximal score of each joint was added into a Global OMERACT-EULAR Synovitis Score (GLOESS) for bilateral metacarpophalangeal joints (MCPs) 2-5 (primary objective). The value of GLOESS containing other joint sets was explored, along with clinical efficacy.

Results: Eighty-nine patients completed the 24-week treatment period. The earliest PDUS sign of improvement in synovitis was at week 1 (mean change in GLOESS (MCPs 2-5): -0.7 (95% CIs -1.2 to -0.1)), with continuous improvement to week 24. Early improvement was observed in the component scores (power Doppler signal at week 1, synovial hyperplasia at week 2, joint effusion at week 4). Comparable changes were observed for 22 paired joints and minimal joint subsets. Mean Disease Activity Score 28 (C reactive protein) was significantly reduced from weeks 1 to 24, reaching clinical meaningful improvement (change ≥1.2) at week 8.

Conclusions: In this first international prospective study, the composite PDUS score is responsive to abatacept. GLOESS demonstrated the rapid onset of action of abatacept, regardless of the number of joints examined. Ultrasound is an objective tool to monitor patients with RA under treatment.

Trial registration number: NCT00767325.

Keywords: DMARDs (biologic); Disease Activity; Rheumatoid Arthritis; Ultrasonography.

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Figures

Figure 1

Patient disposition for all patients who received at least one dose of study drug (N=104). Owing to compliance issues (major deviation due to the lack of participation in training), patients from one site (n=8) were excluded before power Doppler and greyscale ultrasound analyses were performed.

Figure 2

Mean change in (A) GLOESS and the component scores for metacarpophalangeal joints 2–5, (B) GLOESS for the 22-paired joint set, (C) GLOESS for the reduced (nine-paired) joint set and (D) DAS28 (CRP) >24 weeks of treatment with abatacept plus methotrexate. Error bars represent 95% CIs. Data are for patients with baseline and at least one postbaseline assessment, with last observation carried forward. PDUS analyses were completed for 96 of the 104 patients, as patients from one site (n=8) were excluded due to compliance issues. (A) CI did not cross zero from week 1 for GLOESS: −0.7 (−1.2 to −0.1) or power Doppler: −0.9 (−1.5 to −0.3); CI did not cross zero from week 2 for synovial hyperplasia: −1.0 (−1.6 to −0.4); CI did not cross zero from week 4 for joint effusion: −0.8 (−1.4 to −0.3). (B) CI did not cross zero from week 1 −1.7 (−3.4 to −0.1). (C) CI did not cross zero from week 2 −1.5 (−2.4 to −0.6). (D) CI did not cross zero from week 1 −0.5 (−0.7 to −0.4). CMI, clinically meaningful improvement (ie, improvement from baseline in DAS28 score of ≥1.2); CRP, C reactive protein; DAS, disease activity score; GLOESS, Global OMERACT–EULAR (Outcome Measures in Rheumatology–European League Against Rheumatism) Synovitis Score; PDUS, power Doppler and greyscale ultrasound.