Changes in Ultrasonographic Vascularity Upon Initiation of Adalimumab Combination Therapy in Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate

Abstract

Objective: To assess joint disease activity by ultrasound (US) in patients with rheumatoid arthritis (RA) initiating treatment with adalimumab (ADA) plus methotrexate (MTX).

Methods: Data for this post hoc analysis originated from the MUSICA trial (ClinicalTrials.gov identifier: NCT01185288), which evaluated the efficacy of initiating ADA (40 mg every other week) plus 7.5 or 20 mg/week MTX in 309 patients with RA with an inadequate response to MTX. Synovial vascularization over 24 weeks was assessed bilaterally at metacarpophalangeal joint 2 (MCP2), MCP3, MCP5, metatarsophalangeal joint 5, and the wrists by power Doppler US (PDUS). A semiquantitative 4-grade scale was used. Disease activity was assessed using the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) and Simplified Disease Activity Index (SDAI). The correlation between continuous variables was assessed using Pearson's correlation coefficient.

Results: After 24 weeks of treatment with ADA plus MTX, rapid improvements in the mean synovial vascularity score were observed; the greatest improvements were in MCP2 (-0.5), MCP3 (-0.4), and the wrist (-0.4). At week 24, patients with the lowest DAS28-CRP (<2.6) had the lowest mean 5-joint and 3-joint composite synovial vascularity scores. The 5-joint and 3-joint scores were strongly correlated (ρ > 0.9). Synovial vascularity scores correlated poorly with DAS28, swollen joint count in 66 joints (SJC66), SJC28, tender joint count in 68 joints (TJC68), TJC28, Clinical Disease Activity Index (CDAI), SDAI, physician's global assessment, patient's global assessment of pain, and disease duration (ρ < 0.2). Thirty-two (70%) of 46 patients with a DAS28-CRP of <2.6, and 11 (58%) of 19 patients with an SDAI indicating remission had at least 1 joint with a synovial vascularity score of ≥1.

Conclusion: PDUS detects changes in synovial vascularity in RA patients treated with ADA plus MTX, and residual synovial vascularity in patients in whom clinical disease control has been achieved.

© 2016 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

Figures

Figure 1

A, Mean synovial vascularity score for metacarpophalangeal joint 2 (MCP2), MCP3, MCP5, metatarsophalangeal joint 5 (MTP5), and the wrist in patients with rheumatoid arthritis at baseline and at weeks 4, 8, 12, 16, 20, and 24 of treatment with adalimumab plus methotrexate. B, Percentage of total change at each joint from baseline to week 24 accounted for by change in dorsal and volar views. C, Percentage of joints with a synovial vascularity score of ≥2 at baseline and week 24. Bilateral dorsal (dorsal left [Dor‐L] and dorsal right) and volar (volar left [Vol‐L] and volar right) scoring was performed for MCP2, MCP3, and MCP5; only dorsal scoring was performed for MTP5 and the wrist. Scores are from the primary reader. Analysis was based on as‐observed cases. ∗ = P < 0.05; ∗∗ = P < 0.01; ∗∗∗ = P < 0.001 versus week 24, by chi‐square test. D, Percentage of patients with a synovial vascularity score of ≤1 at baseline and week 24. ∗ = P < 0.05 by chi‐square test.

Figure 2

Changes in mean synovial vascularity scores in patients with rheumatoid arthritis over 24 weeks of treatment. A, Changes in mean 5‐joint composite synovial vascularity scores over 24 weeks of treatment. Patients were divided into subgroups based on Disease Activity Score in 28 joints using the C‐reactive protein level (DAS28‐CRP). Values at the top are the number of patients in each DAS28‐CRP group at each time point. Bilateral 5‐joint scores for as‐observed cases are shown. Scores are from primary reader results. Scores at baseline and week 24 are the average of those from 2 readers. B, Changes in synovial vascularity scores from baseline to week 24. Patients were divided into subgroups based on week 24 DAS28‐CRP. Symbols show the mean; horizontal lines indicate the 95% confidence interval. MCP3 = metacarpophalangeal joint 3.