5 research outputs found
Clinical signs and symptoms of Wilson disease in a real-world cohort of patients in the United States: a medical chart review study
IntroductionThere are limited data from the United States regarding the real-world signs and symptoms of Wilson disease (WD). This retrospective, observational medical chart review was conducted to identify real-world characteristics of patients with WD in the United States, as well as WD signs and symptoms at diagnosis and over time.MethodsDe-identified clinical data were abstracted from medical charts of US patients diagnosed with WD between January 1, 2012, and June 30, 2017. Hepatic, neurologic, and psychiatric biochemical findings, signs, and symptoms were characterized at diagnosis and follow-up/during treatment.ResultsIn total, 225 WD patients were included in the study. The mean (SD) age at diagnosis was 24.7 (9.8) years, and 65.3% were male. Median (Q1âQ3) follow-up after diagnosis was 39.5 (33.8â60.4) months. The most common disease presentation at WD diagnosis was combined neurologic/psychiatric and hepatic (52.9%), followed by neurologic/psychiatric (20.0%), hepatic (16.9%), and asymptomatic (10.2%). Common clinical characteristics at diagnosis were Kayser-Fleischer rings (77.2%), low ceruloplasmin levels (95.2%), high hepatic copper (97.8%), elevated 24-hour urinary copper excretion (90.2%), and abnormal liver function tests (38.7%â85.1%). At diagnosis, the most common biochemical findings or hepatic sign/symptoms were abnormal liver enzymes (50.7%), abdominal pain (16.6%), and fatigue (15.7%). The most common neurologic signs/symptoms were headache (18.3%), dysarthria (17.4%), and ataxia (17.0%). Common psychiatric signs/symptoms included anxiety/depression/other mood changes (36.2%), emotional lability (12.8%), and increased irritability/anger outbursts (9.2%). Prevalence of biochemical abnormalities or signs/symptoms among patients at diagnosis and after ~1-year follow-up were neurologic (60.1% and 44.0%), hepatic (69.6% and 37.8%), and psychiatric (53.7% and 37.6%), respectively. Common new onset symptoms at ~1-year post-WD diagnosis were abnormal liver enzymes (5.6%), headache (6.2%), and anxiety/depression/other mood changes (7.2%).ConclusionsThese real-world, descriptive data highlight the clinical complexity and heterogeneity of WD and the need for better education about diagnostic testing and multidisciplinary support. Although rare, the neurologic, psychiatric, and hepatic signs/symptoms of WD have a substantial clinical impact
Quality-adjusted time without symptoms of disease or toxicity and quality-adjusted progression-free survival with niraparib maintenance in first-line ovarian cancer in the PRIMA trial
Background: The PRIMA phase 3 trial showed niraparib significantly prolongs median progression-free survival (PFS) versus placebo in patients with advanced ovarian cancer (OC) responsive to first-line platinum-based chemotherapy, including those who had tumors with homologous recombination deficiency (HRd). This analysis of PRIMA examined the quality-adjusted PFS (QA-PFS) and quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) of patients on maintenance niraparib versus placebo. Methods: Patients were randomized 2:1 to receive once-daily maintenance niraparib (n = 487) or placebo (n = 246). QA-PFS was defined as the PFS of patients adjusted for their health-related quality of life (HRQoL) prior to disease progression, measured using European Quality of Life Five-Dimension (EQ-5D) questionnaire index scores from the PRIMA trial. Q-TWiST was calculated by combining data on PFS, duration of symptomatic grade â©Ÿ2 adverse events (fatigue or asthenia, nausea, vomiting, abdominal pain, and abdominal bloating) prior to disease progression, and EQ-5D index scores. Analyses used data collected up to the last date of PFS assessment (May 17, 2019). Results: The restricted mean QA-PFS was significantly longer with niraparib versus placebo in the HRd (n = 373) and overall intention-to-treat (ITT; n = 733) populations (mean gains of 6.5 [95% confidence interval; CI, 3.9â8.9] and 4.1 [95% CI, 2.2â5.8] months, respectively). There were also significant improvements in restricted mean Q-TWiST for niraparib versus placebo (mean gains of 5.9 [95% CI, 3.5â8.6] and 3.5 [95% CI, 1.7â5.6] months, respectively) in the HRd and ITT populations. Conclusions: In patients with advanced OC, first-line niraparib maintenance was associated with significant gains in QA-PFS and Q-TWiST versus placebo. These findings demonstrate that niraparib maintenance treatment is associated with a PFS improvement and that treatment benefit is maintained even when HRQoL and/or toxicity data are combined with PFS in a single measure. Trial registration: ClinicalTrials.gov: NCT02655016; trial registration date: January 13, 2016 Plain language summary: Background: In a large clinical trial called PRIMA, patients with advanced cancer of the ovary (ovarian cancer) were given either niraparib (a type of cancer medicine) or placebo (a pill containing no medicine/active substances) after having chemotherapy (another type of cancer medicine). Taking niraparib after chemotherapy is called maintenance therapy and aims to give patients more time before their cancer returns or gets worse than if they were not given any further treatment. In the PRIMA trial, patients who took niraparib did have more time before their cancer progressed than if they took placebo. However, it is important to consider patientsâ quality of life, which can be made worse by cancer symptoms and/or side effects of treatment. Here, we assessed the overall benefit of niraparib for patients in PRIMA. Methods: Both the length of time before disease progression (or survival time) and quality of life were considered using two different analyses: ââThe first analysis was called quality-adjusted PFS (QA-PFS) and looked at how long patients survived with good quality of life. ââThe second analysis was called quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) and looked at how long patients survived without cancer symptoms or treatment side effects. Results: The PRIMA trial included 733 patients; 487 took niraparib and 246 took placebo. Around half of the patients in both groups had a type of ovarian cancer that responds particularly well to drugs like niraparib â they are known as homologous recombination deficiency (HRd) patients. ââWhen information on quality of life (collected from patient questionnaires) and survival was combined in the QA-PFS analysis, HRd patients who took niraparib had approximately 6.5 months longer with a good quality of life before disease progression than those who took placebo. In the overall group of patients (including HRd patients and non-HRd patients), those who took niraparib had approximately 4 months longer than with placebo. ââUsing the second analysis (Q-TWiST) to combine information on survival with cancer symptoms and treatment side effects, the HRd patients taking niraparib had approximately 6 months longer without cancer symptoms or treatment side effects (such as nausea or vomiting) than patients taking placebo. In the overall group of patients, those taking niraparib had approximately 3.5 months longer without these cancer symptoms/side effects than patients receiving placebo. Conclusions: These results show that the survival benefits of niraparib treatment remain when accounting for patientsâ quality of life. These benefits were seen not only in HRd patients who are known to respond better to niraparib, but in the overall group of patients who took niraparib.publishedVersionPeer reviewe
Real-world treatment patterns and outcomes in hepatorenal syndrome: results from a retrospective chart review study in the United Kingdom
sj-docx-2-tam-10.1177_17588359221126149 â Supplemental material for Quality-adjusted time without symptoms of disease or toxicity and quality-adjusted progression-free survival with niraparib maintenance in first-line ovarian cancer in the PRIMA trial
Supplemental material, sj-docx-2-tam-10.1177_17588359221126149 for Quality-adjusted time without symptoms of disease or toxicity and quality-adjusted progression-free survival with niraparib maintenance in first-line ovarian cancer in the PRIMA trial by Maria-Pilar Barretina-Ginesta, Bradley J. Monk, Sileny Han, Bhavana Pothuri, Annika Auranen, Dana M. Chase, Domenica Lorusso, Charles Anderson, Sophie Abadie-Lacourtoisie, Noelle Cloven, Elena I. Braicu, Amnon Amit, AndrĂ©s Redondo, Ruchit Shah, Nehemiah Kebede, Carol Hawkes, Divya Gupta, Tatia Woodward, David M. OâMalley and Antonio GonzĂĄlez-MartĂn in Therapeutic Advances in Medical Oncology</p
sj-docx-1-tam-10.1177_17588359221126149 â Supplemental material for Quality-adjusted time without symptoms of disease or toxicity and quality-adjusted progression-free survival with niraparib maintenance in first-line ovarian cancer in the PRIMA trial
Supplemental material, sj-docx-1-tam-10.1177_17588359221126149 for Quality-adjusted time without symptoms of disease or toxicity and quality-adjusted progression-free survival with niraparib maintenance in first-line ovarian cancer in the PRIMA trial by Maria-Pilar Barretina-Ginesta, Bradley J. Monk, Sileny Han, Bhavana Pothuri, Annika Auranen, Dana M. Chase, Domenica Lorusso, Charles Anderson, Sophie Abadie-Lacourtoisie, Noelle Cloven, Elena I. Braicu, Amnon Amit, AndrĂ©s Redondo, Ruchit Shah, Nehemiah Kebede, Carol Hawkes, Divya Gupta, Tatia Woodward, David M. OâMalley and Antonio GonzĂĄlez-MartĂn in Therapeutic Advances in Medical Oncology</p