Background The global power Doppler ultrasound (PDUS) scoring system combining synovial hypertrophy, joint effusion and PD signal developed by the OMERACT-EULAR-US Task Force has good intra- and inter-observer reliability in metacarpophalangeal (MCP) and non-MCP joints and demonstrates consistency between PDUS machines.1 We present the first international, Phase IIIb study using the global PDUS synovitis score to assess early impact of IV abatacept (ABA) on synovial inflammation.
Objectives Primary objective: to evaluate early response to ABA, defined by improvement of synovitis assessed by global PDUS of affected MCP joints bilaterally.
Methods This 6-mth, single-arm, open-label study enrolled active MTX-IR RA patients (pts) defined as DAS28 (CRP) >3.2 or ≥6 tender and swollen joints and CRP >ULN. Pts had a total synovitis PDUS score >1 for ≥2 MCPs and ≥1 for ≥1 other MCP (out of MCP 2–5 bilaterally; i.e. 8 joints) at screening and baseline (BL). Global PDUS was scored over 8 MCP joints (range 0–24 units) at BL, Days 7, 15, 29, 43 and 57 then monthly by a PDUS reader blinded from clinical assessments. Early signs of improvement were defined as the earliest timepoint when 95%CI for mean change from BL in global PDUS score did not contain 0 for that and all later timepoints. DAS28 (CRP) and safety were assessed for all pts who received ≥1 dose of ABA.
Results 104 pts were enrolled; 89 completed the trial. Demographic, clinical and PDUS data are shown (Table). Early signs of improvement in global PDUS score were observed at Day 7. Mean change from BL in global PDUS score and its components increased to Day 169. By Day 57, threshold for clinically meaningful improvement of 1.2 was not included in the 95% CI for mean change from BL in DAS28 (CRP). There were no deaths; 6 (5.8%) pts developed a SAE (atrial fibrillation, bursitis, dementia, endometriosis, pleural effusion and pulmonary fistula, and hypertension), 62 (59.6%) an AE, and 20 (19.2%) an infection.
Conclusions The study showed that the OMERACT-EULAR-US global PDUS score detected early signs of improvement in synovitis, demonstrating a significant response to abatacept at Day 7, which increased to Mth 6. Efficacy and safety data were consistent with a previous abatacept trial in MTX-IR pts.2
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Conaghan P et al. Ann Rheum Dis 2011;70(S3):151.
Disclosure of Interest M. D’Agostino: None Declared, R. Wakefield: None Declared, H. Berner Hammer: None Declared, O. Vittecoq: None Declared, M. Galeazzi: None Declared, P. Balint Grant/Research support from: Bristol-Myers Squibb, Speakers Bureau: Abbott, Pfizer, MSD, Roche, SonoSite, GE, ESAOTE, ACR, EULAR, E. Fillipucci Consultant for: Bristol-Myers Squibb, I. Moller: None Declared, A. Iagnocco: None Declared, E. Naredo Grant/Research support from: Merck Sharp & Dohme Corp, M. Ostergaard Grant/Research support from: Abbott, Amgen, Bristol-Myers Squibb, Centocor, Genmab, Glaxo-Smith-Kline, Mundipharma, Novo, Pfizer, Roche, Schering-Plough, UCB and Wyeth, Consultant for: Abbott, Amgen, Bristol-Myers Squibb, Centocor, Genmab, Glaxo-Smith-Kline, Mundipharma, Novo, Pfizer, Roche, Schering-Plough, UCB and Wyeth, Speakers Bureau: Abbott, Amgen, Bristol-Myers Squibb, Centocor, Genmab, Glaxo-Smith-Kline, Mundipharma, Novo, Pfizer, Roche, Schering-Plough, UCB and Wyeth, C. Gaillez Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, W. Kerselaers Employee of: Bristol-Myers Squibb, K. Van Holder Employee of: Bristol-Myers Squibb, M. Le Bars Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb