Background/Purpose: Cardiovascular disease (CVD) is the leading cause of death in patients (pts) with rheumatoid arthritis (RA). Adiponectin has been shown to have anti-inflammatory and atheroprotective effects on the vasculature, with higher levels associated with improved insulin sensitivity, lower triglyceride levels, and less atherosclerosis. The effect of tocilizumab (TCZ) on adiponectin level has not been studied. The purpose of this study was to explore the change in adiponectin level associated with treatment with TCZ and response to treatment.

Methods: Pts from the MEASURE study (moderate to severe RA with inadequate response to methotrexate [MTX]) who received randomized treatment with either TCZ 8 mg/kg or placebo (PBO) plus MTX were examined if they had fasting adiponectin samples at baseline and week 24. Demographics, RA disease parameters, CVD risk factors, and laboratory assessments of fasting lipids and leptin were assessed at baseline and after 24 weeks of treatment. Within-group change was examined using paired t-tests. All association analyses were conducted using linear regression, adjusted for age and sex.

Results: Baseline and week 24 adiponectin samples were available for 108/132 pts, with equal allocation to TCZ + MTX and PBO + MTX. Median (IQR) age was 56 (49-63) years, and median (IQR) body mass index (BMI) was 29 (26-33) kg/m². Median (IQR) baseline fasting adiponectin level was 11.2 (7.5-17.7) mg/mL. Baseline characteristics did not significantly differ according to treatment allocation. At baseline, older and female pts were more likely to have higher adiponectin levels, whereas those with higher BMI and/or diabetes were more likely to have lower adiponectin levels. Baseline inflammatory disease activity (DAS28 and C-reactive protein) was not significantly associated with baseline adiponectin. Pts treated with TCZ + MTX had a significant increase in adiponectin by an average of +10% (Table). There was no change in adiponectin among the PBO + MTX group (mean change [95% CI]: 0.25 [–0.54, 1.28]). There was no significant change in leptin or BMI in the TCZ + MTX group. No baseline variables showed significant association with change in adiponectin; however, among pts treated with TCZ + MTX, higher increase in adiponectin level was associated with greater increase in total cholesterol level (β=1.00; p<0.05) and larger improvement in disease activity (β for association for DAS28ESR=–0.67; p<0.05). Increasing adiponectin levels paralleled increases in both LDL and HDL levels and increases in proatherogenic (ApoB) and anti-atherogenic (ApoA-1) apolipoproteins (Table).

Conclusion : Adiponectin is increased with TCZ treatment in RA pts, with higher increases observed in pts with greater degrees of RA disease activity suppression. Future studies should confirm whether TCZ increases adiponectin level and, if so, whether adiponectin change predicts CVD risk change with TCZ.