RESUMO
The original version of this article unfortunately contained a mistake.
RESUMO
Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, debilitating disease often resulting in early-onset, life-impacting autonomic dysfunction. The effect of the RNAi therapeutic, patisiran, on autonomic neuropathy manifestations in patients with hATTR amyloidosis with polyneuropathy in the phase III APOLLO study is reported. Patients received patisiran 0.3 mg/kg intravenously (n = 148) or placebo (n = 77) once every 3 weeks for 18 months. Patisiran halted or reversed polyneuropathy and improved quality of life from baseline in the majority of patients. At baseline, patients in APOLLO had notable autonomic impairment, as demonstrated by the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire and Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire autonomic neuropathy domain. At 18 months, patisiran improved autonomic neuropathy symptoms compared with placebo [COMPASS-31, least squares (LS) mean difference, - 7.5; 95% CI: - 11.9, - 3.2; Norfolk QOL-DN autonomic neuropathy domain, LS mean difference, - 1.1; - 1.8, - 0.5], nutritional status (modified body mass index, LS mean difference, 115.7; - 82.4, 149.0), and vasomotor function (postural blood pressure, LS mean difference, - 0.3; - 0.5, - 0.1). Patisiran treatment also led to improvement from baseline at 18 months for COMPASS-31 (LS mean change from baseline, - 5.3; 95% CI: - 7.9, - 2.7) and individual domains, orthostatic intolerance (- 4.6; - 6.3, - 2.9) and gastrointestinal symptoms (- 0.8; - 1.5, - 0.2). Rapid worsening of all study measures was observed with placebo, while patisiran treatment resulted in stable or improved scores compared with baseline. Patisiran demonstrates benefit across a range of burdensome autonomic neuropathy manifestations that deteriorate rapidly without early and continued treatment.
Assuntos
Neuropatias Amiloides Familiares/tratamento farmacológico , Doenças do Sistema Nervoso Autônomo/tratamento farmacológico , RNA Interferente Pequeno/uso terapêutico , Adulto , Neuropatias Amiloides Familiares/complicações , Doenças do Sistema Nervoso Autônomo/etiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polineuropatias/tratamento farmacológico , Polineuropatias/etiologia , Qualidade de Vida , Terapêutica com RNAi/métodosRESUMO
OBJECTIVES: To assess the impact of a discharge diagnosis of critical illness polyneuromyopathy on health-related outcomes in a large cohort of patients requiring ICU admission. DESIGN: Retrospective cohort with propensity score-matched analysis. SETTING: Analysis of a large multihospital database. PATIENTS: Adult ICU patients without preexisting neuromuscular abnormalities and a discharge diagnosis of critical illness polyneuropathy and/or myopathy along with adult ICU propensity-matched control patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 3,567 ICU patients with a discharge diagnosis of critical illness polyneuropathy and/or myopathy, we matched 3,436 of these patients to 3,436 ICU patients who did not have a discharge diagnosis of critical illness polyneuropathy and/or myopathy. After propensity matching and adjusting for unbalanced covariates, we used conditional logistic regression and a repeated measures model to compare patient outcomes. Compared to patients without a discharge diagnosis of critical illness polyneuropathy and/or myopathy, patients with a discharge diagnosis of critical illness polyneuropathy and/or myopathy had fewer 28-day hospital-free days (6 [0.1] vs 7.4 [0.1] d; p < 0.0001), had fewer 28-day ventilator-free days (15.7 [0.2] vs 17.5 [0.2] d; p < 0.0001), had higher hospitalization charges (313,508 [4,853] vs 256,288 [4,470] dollars; p < 0.0001), and were less likely to be discharged home (15.3% vs 32.8%; p < 0.0001) but had lower in-hospital mortality (13.7% vs 18.3%; p < 0.0001). CONCLUSIONS: In a propensity-matched analysis of a large national database, a discharge diagnosis of critical illness polyneuropathy and/or myopathy is strongly associated with deleterious outcomes including fewer hospital-free days, fewer ventilator-free days, higher hospital charges, and reduced discharge home but also an unexpectedly lower in-hospital mortality. This study demonstrates the clinical importance of a discharge diagnosis of critical illness polyneuropathy and/or myopathy and the need for effective preventive interventions.