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

OBJECTIVE: 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 8 mg/kg). METHODS: Fifty-four RA patients starting IV-TCZ were evaluated at baseline, 4, 6, 12, 16, and 24 weeks 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. RESULTS: Ninety-four percent of patients required dose escalation to 8 mg/kg. US34-PDUS, CDAI, and DAS28-ESR improved significantly over 24 weeks (p < 0.001). Baseline PDUS and 12-week PDUS change correlated with CDAI at 24 weeks (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. CONCLUSION: RA patients treated with IV-TCZ for 24 weeks 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 4 mg/kg may not be sufficient to attain low RA disease activity at 12 weeks, in RA patients with moderate to severe disease (DAS28 ≥ 4.4 and US34-PDUS ≥ 10). TRIAL REGISTRATION: 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 8 mg/kg at 12 weeks. • Reduction in power Doppler ultrasonography (US34-PDUS) scores correlate with DAS28-ESR and CDAI over 24 weeks 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.

Prophylactic catheter ablation of ventricular tachycardia in ischemic cardiomyopathy: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Catheter ablation is proven to be an effective strategy for drug refractory ventricular tachycardia (VT) in ischemic cardiomyopathy. However, the appropriate timing of VT ablation and identifying the group of patients that may receive the greatest benefit remains uncertain. There is limited data on the effect on prophylactic catheter ablation (PCA) in the prevention of implantable cardioverter defibrillator (ICD) therapy, electrical storm, and mortality. METHODS: We performed a comprehensive literature search through November 1, 2017, for all eligible studies comparing PCA + ICD versus ICD only in eligible patients with ischemic cardiomyopathy. Clinical outcomes included all ICD therapies including ICD shocks and electrical storm. Additional outcomes included all-cause mortality, cardiovascular mortality, and complications. RESULTS: Three randomized controlled trials (RCTs) (N = 346) met inclusion criteria. PCA was associated with a significantly lower ICD therapies (OR 0.49; CI 0.28 to 0.87; p = 0.01) including ICD shocks [OR 0.38; CI 0.22 to 0.64; p = 0.0003) and electrical storm (OR 0.55; CI 0.30 to 1.01; p = 0.05) when compared with ICD only. There was no significant difference in all-cause mortality (OR 0.77; CI 0.41 to 1.46; p = 0.42), cardiovascular mortality (OR 0.49; CI 0.16 to 1.50; p = 0.21), and major adverse events (OR 1.45; CI 0.52 to 4.01; p = 0.47) between two groups. CONCLUSION: These results suggest prophylactic catheter ablation decreases ICD therapies, including shocks and electrical storm with no improvement in overall mortality. There is a need for future carefully designed randomized clinical trials.