RESUMO
Background: Opioid-induced constipation (OIC) may increase the risk of fecal impaction and mortality in patients with advanced illness. Methylnaltrexone (MNTX) is efficacious for OIC. Objective: The purpose of this analysis was to evaluate cumulative rescue-free laxation response with repeat MNTX dosing in patients with advanced illness who were refractory to current laxative regimens and to assess the influence, if any, of poor functional status on response to MNTX treatment. Methods: This analysis included pooled data from patients with advanced illness and established OIC who were on a stable opioid regimen in a pivotal, randomized, placebo (PBO)-controlled clinical trial (study 302 [NCT00402038]) or a randomized, PBO-controlled Food and Drug Administration-required postmarketing study (study 4000 [NCT00672477]). Patients in study 302 received subcutaneous MNTX 0.15 mg/kg or PBO every other day, whereas those in study 4000 received MNTX 8 mg (body weight ≥38 to <62 kg), MNTX 12 mg (body weight ≥62 kg), or PBO every other day. Outcomes included cumulative rescue-free laxation rates at 4- and 24-hours postdose for the first 3 doses of study drug and time to rescue-free laxation. To assess if functional status influenced treatment outcomes, we performed a secondary analysis on the outcomes stratified by baseline World Health Organization/Eastern Cooperative Oncology Group performance status, pain scores, and safety. Results: One hundred eighty-five patients received PBO and 179 patients received MNTX. The median age was 66.0 years, 51.5% were women, 56.5% had a baseline World Health Organization/Eastern Cooperative Oncology Group performance status score >2, and 63.4% had a primary diagnosis of cancer. Cumulative rescue-free laxation rates were significantly higher with MNTX than PBO 4- and 24-hours after doses 1, 2, and 3 (P < 0.0001), and between-treatment comparisons remained significant (P < 0.0001) regardless of performance status. The estimated time to first rescue-free laxation was shorter for patients receiving MNTX versus PBO. No new safety signals were identified. Conclusions: Repeated use of MNTX represents a safe and effective treatment for OIC in patients with advanced illness regardless of baseline performance status. ClinicalTrials.gov identifier: NCT00672477. (Curr Ther Res Clin Exp. 2023; 84:XXX-XXX)© 2023 Elsevier HS Journals, Inc.
RESUMO
Uncontrolled asthma in the elderly is a public health issue recognized in developed countries such as the United States and among the European Union, both from patient safety and economic perspectives. Variations in the cutoff, which defines elderly age, contribute to epidemiological study difficulties. Nonetheless, the relevance of elderly asthma from a socioeconomic perspective is inarguable. The projected growth of the enlarging geriatric population in the United States portends an impending national health burden that may or may not be preventable with pharmacologic and non-pharmacologic treatments. Asthma in the elderly might be a consequence of uncontrolled disease that is carried throughout a lifetime. Or elderly asthmatics could suffer from uncontrolled asthma, which overlaps with other ailments common with advancing ages that merit consideration, eg, COPD, heart disease, OSA, diabetes mellitus, and other comorbidities. Because of the heterogeneity of asthma phenotypes and other conditions that could mimic the symptoms of elderly asthma, further cohort studies are needed to elucidate the elderly asthmatic pathophysiology and management. More studies to characterize elderly asthma can help address these patients' unmet need for evidence-based guidelines. We introduce the 5 "Ps" (phenotypes, partnership, pharmacology, practice in acute exacerbations, and problems or barriers for the elderly asthmatics) that establish a framework approach for clinical practice.
