Doppler ultrasound impacts response to intravenous tocilizumab in rheumatoid arthritis patients.

Abstract

Within rheumatoid arthritis (RA) patients treated with intravenous tocilizumab (IV-TCZ), it is unclear if power Doppler ultrasonography (PDUS) can predict future clinical response. This study sought to determine if baseline PDUS or its early changes can predict 12-week and 24-week disease activity outcomes, and quantify the need for dose escalation (4 to 8mg/kg). Fifty-four RA patients starting IV-TCZ were evaluated at baseline, 4, 6, 12, 16, and 24weeks using 34-joint PDUS (US34-PDUS), clinical disease activity index (CDAI), 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR), ACR 20/50/70, health assessment questionnaire-disability index (HAQ-DI), and PDUS 20/50/70, a novel measure. Logistic regression models evaluated the predictive utility of US34-PDUS of DAS28-ESR response after adjusting for covariates. Ninety-four percent of patients required dose escalation to 8mg/kg. US34-PDUS, CDAI, and DAS28-ESR improved significantly over 24weeks (p < 0.001). Baseline PDUS and 12-week PDUS change correlated with CDAI at 24weeks (p < 0.05). Logistic regression demonstrated baseline US34-PDUS was independently associated with DAS28-ESR ≥ 1.2 response, even after adjusting for baseline DAS28-ESR (p = 0.03). CDAI, DAS28-ESR, and their components increased across PDUS 20/50/70 categories; however, HAQ-DI did not. RA patients treated with IV-TCZ for 24weeks demonstrated significant improvement, and baseline/early changes in PDUS were predictive of later clinical response. The PDUS 20/50/70 measure is a novel metric of response. This study suggests that IV-TCZ 4mg/kg may not be sufficient to attain low RA disease activity at 12weeks, in RA patients with moderate to severe disease (DAS28 ≥ 4.4 and US34-PDUS ≥ 10). ClinicalTrials.gov NCT01717859 Key Points • Over 90% of RA patients with baseline DAS28-ESR ≥ 4.4 and PDUS34 ≥ 10 required intravenous tocilizumab dose escalation from 4 to 8mg/kg at 12weeks. • Reduction in power Doppler ultrasonography (US34-PDUS) scores correlate with DAS28-ESR and CDAI over 24weeks in rheumatoid arthritis patients with moderate to severe disease activity. • Baseline US34-PDUS predicts future improvements in clinical disease activity outcomes, independent of baseline DAS28-ESR. • Clinical response measures, DAS28-ESR and CDAI, improved across US34-PDUS 20/50/70 categories, while patient-reported outcomes did not.