Background/Purpose: Musculoskeletal ultrasound (MSUS) can detect synovitis by Power doppler (PDUS) and can predict erosive progression on xrays in rheumatoid arthritis (RA) patients. We previously reported an association of active RA with impairment in HDL function, changes in HDL-associated protein levels, and suppression of paraoxonase-1 (PON1) activity, a novel risk factor for cardiovascular disease (CVD), which has been associated with carotid plaque in RA patients. In the current work, we evaluated an association of tocilizumab treatment with PDUS changes and the “protective profile” of HDL including HDL’s ability to inhibit low density lipoprotein (LDL) oxidation, PON1 activity, HDL-associated apoA-I (HDL-apoA-I) and haptoglobin (HDL-Hp) in patients with RA.

Methods: Assessment of PDUS was performed on 46 RA patients in a 6 month (mos) open-label study of IV tocilizumab initiated at 4mg/kg and dose escalated to 8mg/kg if DAS28>3.2 at 12wks. 34 joints were scanned by MSUS (bilateral wrists, MCP1-5, PIP1-5, knees, and MTP2-5). PDUS was scored semiquantitatively according to published consensus definitions (J Rheum. 2005;32:2485-7). HDL’s anti-oxidant function was measured by a cell free assay as described previously (A&R 2009; 60(10): 2870-9). PON1 activity was measured by previously published assays and HDL-associated apoA-I and Hp were measured by sandwich ELISA.

Results: Treatment with tocilizumab for 6 mos was associated with increases in traditional cholesterol levels including significant increases in HDL-C (baseline: 59± 23mg/dL; 6 mos: 71 ± 26 mg/dL, p<0.05), and improvements in HDL’s overall antioxidant function (baseline: 2347± 1710 FU; 6 mos: 1570 ± 1050 FU, p<0.05), increases in PON1 activity (baseline: 10.2± 3.8; 6 mos: 11.9 ± 4.4 , p<0.05), and trends for increases in HDL-apoA-I levels and decreases in HDL-Hp (p values >0.05). Greater decreases in PDUS scores over 6 mos were significantly associated with greater improvements in the HDL particle profile including increases in HDL-C (r= -0.32, p<0.05), PON1 activity (r= -0.30, p<0.05), HDL-apoA-I (r= -0.31, p<0.05), HDL’s anti-oxidant capacity (r= 0.38, p= 0.009) and trends for decreases in HDL-Hp (r= 0.24, p= 0.11). Associations between other disease assessments (DAS28 and CDAI) and HDL function/structure were noted, but were generally of lesser magnitude and consistency across the HDL profile. Increases in total and HDL-C levels with tocilizumab treatment were strongly correlated with improvement in HDL function (r= -0.41, p= 0.005, r= -0.60, p < 0.0001) and PON1 activity (r= 0.73, p< 0.0001, r= 0.43, p = 0.003).

Conclusion: Improvements in PDUS scores with tocilizumab treatment were significantly associated with improvements in the protective profile of HDL including increased HDL’s anti-oxidant capacity, PON1 activity, and HDL-apoA-I levels. This data supports previous work suggesting a direct association of joint inflammation with abnormal HDL function, and suggests that further evaluation of PDUS as a non-invasive CV risk assessment tool in RA may be warranted.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/reduction-in-power-doppler-ultrasound-score-with-tocilizumab-treatment-associates-with-improvement-in-the-protective-profile-of-hdl-in-patients-with-rheumatoid-arthritis/