Background Control of disease activity in patients with rheumatoid arthritis (RA) has become achievable using synthetic and biologic disease modifying anti-rheumatic drugs, both as monotherapy or in combination. However, residual inflammatory disease can be revealed by sensitive imaging techniques such as ultrasonography in patients with remission of disease activity.
Objectives To evaluate ultrasonographic vascularity changes in the joints of RA patients with previous methotrexate (MTX) inadequate-response upon initiation of adalimumab (ADA) combination therapy with two different doses of MTX.
Methods MUSICA was a double-blind, randomized, controlled trial evaluating the efficacy of 2 different dosages of MTX (7.5 or 20 mg/wk) in combination with ADA (40 mg every other wk) for 24 wks in RA patients with previous inadequate response to MTX. Dorsal and volar Power Doppler (PD) images of bilateral metacarpophalangeal (MCP) joints 2, 3, 5, and dorsal images alone of metatarsophalangeal joint 5 (MTP5) and wrists were scored by 2 of 4 independent ultrasound-experienced rheumatologists using a semi-quantitative 4-grade scale. Patients with baseline and wk-24 ultrasonographic images were subgrouped based on 28-joint count disease activity score using C-reactive protein (DAS28[CRP] <2.6, 2.6<3.2, 3.2<5.1, ≥5.1) to compare wk-24 mean vascularity scores and change from baseline.
Results After 24-wk treatment of ADA with 7.5 or 20 mg/wk MTX, rapid decreases in mean synovial vascularity were observed regardless of achievement of disease control, with most improvement occurring within the first 4 wks. The wrist had the most baseline PD activity, 1.6 out of 6. Improvements in vascularity were greatest in MCP2 (-0.5), MCP3 (-0.4), and wrist (-0.4) after 24 wks of ADA + MTX treatment. Dorsal and volar PD vascularity incidence and activity were similar in MCP2, but differed in MCP3 and MCP5 where dorsal imaging encompassed most activity. After 24 wks of ADA + MTX, mean vascularity of the bilateral 5-joint composite score was lowest in patients that achieved DAS28 (CRP) <2.6 (Table), although confidence intervals overlapped with each subgroup. Similarly, a bilateral 3-joint composite score using MCP2, MCP3, and wrist showed lower vascularity scores associated with achievement of lower disease activity. Vascularity for the 5-joint and 3-joint composite scores was not necessarily correlated with improvements in other disease characteristics. Differences comparing MTX treatment groups were minimal whether examining individual joints, 3-, or 5-joint composite scores.
Conclusions Upon initiating ADA in MTX inadequate-responders, rapid reduction in joint vascularity was observed in many patients, regardless of MTX dose. Low overall baseline ultrasonographic vascularity values may have partially reflected suppression of inflammation due to prior MTX treatment. Improvements in vascularity in patients were observed irrespective of achieving low disease activity or remission with a numeric trend for lower mean vascularity in patients achieving lower disease activity.
Acknowledgements AbbVie sponsored the study (NCT01185288), contributed to its design, participated in the collection, analysis, and interpretation of the data, and in the writing, reviewing, and approval of the final version. Statistical support was provided by Shufang Liu, Ph.D., of AbbVie. Medical writing support was provided by Douglas E. Dylla, Ph.D., of AbbVie.
Disclosure of Interest G. Kaeley Consultant for: AbbVie, M. Nishio Speakers bureau: AbbVie, J. Goyal Consultant for: AbbVie, D. MacCarter Consultant for: AbbVie, Speakers bureau: AbbVie, A. Wells Consultant for: AbbVie, A. Cardoso Shareholder of: AbbVie, Employee of: AbbVie, S. Chen Shareholder of: AbbVie, Employee of: AbbVie, J. Kalabic Shareholder of: AbbVie, Employee of: AbbVie, H. Kupper Shareholder of: AbbVie, Employee of: AbbVie