The Effect of Lenalidomide on Health-Related Quality of Life in Patients With Lower-Risk non-del(5q) Myelodysplastic Syndromes: Results From the MDS-005 Study

Abstract Background The phase III MDS-005 study compared lenalidomide versus placebo in red blood cell transfusion-dependent (RBC-TD) patients with lower-risk non-del(5q) myelodysplastic syndromes (MDS), ineligible/refractory to erythropoiesis-stimulating agents. Lenalidomide-treated patients were more likely to achieve transfusion independence (TI) ≥ 8 weeks (26.9% vs. 2.5%; P Patients and Methods Patients were randomized 2:1 to oral lenalidomide 10 mg once daily or placebo once daily (both on 28-day cycles). Patients with creatinine clearance 40 to 60 mL/min were given lenalidomide 5 mg once daily. Health-related quality of life (HRQoL), a predefined secondary end point, was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 questionnaire at baseline, week 12, week 24, every 12 weeks thereafter, and at discontinuation. Results At week 24, lenalidomide was associated with benefit versus placebo across all 5 preselected questionnaire scales (fatigue, dyspnea, global quality of life, physical functioning, and emotional functioning). After adjustment for baseline scores, only emotional functioning achieved significance ( P = .047). Further improvement versus baseline was observed for patients who continued lenalidomide after week 24. In post hoc analyses, achievement of TI ≥ 8 weeks was associated with significant improvements across all scales ( P P Conclusion Lenalidomide did not adversely affect HRQoL in RBC-TD patients with lower-risk non-del(5q) MDS and response to lenalidomide was associated with significant improvements in HRQoL

Treatment sequences for advanced renal cell carcinoma: A health economic assessment.

ObjectiveAdvanced renal cell carcinoma (RCC) is commonly treated with vascular endothelial growth factor or mammalian target of rapamycin inhibitors. As new therapies emerge, interest grows in gaining a deeper understanding of treatment sequences. Recently, we developed a patient-level, discretely integrated condition event (DICE) simulation to estimate survival and lifetime costs for various cancer therapies, using a US payer perspective. Using this model, we explored the impact of treatments such as nivolumab and cabozantinib, and compared the clinical outcomes and cost consequences of commonly used treatment algorithms for patients with advanced RCC.MethodsIncluded treatment sequences were pazopanib or sunitinib as first-line treatment, followed by nivolumab, cabozantinib, axitinib, pazopanib or everolimus. Efficacy inputs were derived from the CheckMate 025 trial and a network meta-analysis based on available literature. Safety and cost data were obtained from publicly available sources or literature.ResultsBased on our analysis, the average cost per life-year (LY) was lowest for sequences including nivolumab (sunitinib → nivolumab, $75,268/LY; pazopanib → nivolumab,$84,459/LY) versus axitinib, pazopanib, everolimus and cabozantinib as second-line treatments. Incremental costs per LY gained were $49,592,$73,927 and $30,534 for nivolumab versus axitinib, pazopanib and everolimus-containing sequences, respectively. The model suggests that nivolumab offers marginally higher life expectancy at a lower cost versus cabozantinib-including sequences.ConclusionTreatment sequences using nivolumab in the second-line setting are less costly compared with sequential use of targeted agents. In addition to efficacy and safety data, cost considerations may be taken into account when considering treatment algorithms for patients with advanced RCC

Florbetaben PET in the Early Diagnosis of Alzheimer's Disease: A Discrete Event Simulation to Explore Its Potential Value and Key Data Gaps

The growing understanding of the use of biomarkers in Alzheimer's disease (AD) may enable physicians to make more accurate and timely diagnoses. Florbetaben, a beta-amyloid tracer used with positron emission tomography (PET), is one of these diagnostic biomarkers. This analysis was undertaken to explore the potential value of florbetaben PET in the diagnosis of AD among patients with suspected dementia and to identify key data that are needed to further substantiate its value. A discrete event simulation was developed to conduct exploratory analyses from both US payer and societal perspectives. The model simulates the lifetime course of disease progression for individuals, evaluating the impact of their patient management from initial diagnostic work-up to final diagnosis. Model inputs were obtained from specific analyses of a large longitudinal dataset from the New England Veterans Healthcare System and supplemented with data from public data sources and assumptions. The analyses indicate that florbetaben PET has the potential to improve patient outcomes and reduce costs under certain scenarios. Key data on the use of florbetaben PET, such as its influence on time to confirmation of final diagnosis, treatment uptake, and treatment persistency, are unavailable and would be required to confirm its value

Application of dynamic modeling for survival estimation in advanced renal cell carcinoma.

OBJECTIVE:In oncology, extrapolation of clinical outcomes beyond trial duration is traditionally achieved by parametric survival analysis using population-level outcomes. This approach may not fully capture the benefit/risk profile of immunotherapies due to their unique mechanisms of action. We evaluated an alternative approach-dynamic modeling-to predict outcomes in patients with advanced renal cell carcinoma. We compared standard parametric fitting and dynamic modeling for survival estimation of nivolumab and everolimus using data from the phase III CheckMate 025 study. METHODS:We developed two statistical approaches to predict longer-term outcomes (progression, treatment discontinuation, and survival) for nivolumab and everolimus, then compared these predictions against follow-up clinical trial data to assess their proximity to observed outcomes. For the parametric survival analyses, we selected a probability distribution based on its fit to observed population-level outcomes at 14-month minimum follow-up and used it to predict longer-term outcomes. For dynamic modeling, we used a multivariate Cox regression based on patient-level data, which included risk scores, and probability and duration of response as predictors of longer-term outcomes. Both sets of predictions were compared against trial data with 26- and 38-month minimum follow-up. RESULTS:Both statistical approaches led to comparable fits to observed trial data for median progression, discontinuation, and survival. However, beyond the trial duration, mean survival predictions differed substantially between methods for nivolumab (30.8 and 51.5 months), but not everolimus (27.2 and 29.8 months). Longer-term follow-up data from CheckMate 025 and phase I/II studies resembled dynamic model predictions for nivolumab. CONCLUSIONS:Dynamic modeling can be a good alternative to parametric survival fitting for immunotherapies because it may help better capture the longer-term benefit/risk profile and support health-economic evaluations of immunotherapies

Impact of Treatment with Naloxegol for Opioid-Induced Constipation on Patients’ Health State Utility

<p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s12325-016-0365-y">https://link.springer.com/article/10.1007/s12325-016-0365-y</a></p><p></p> <p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p

Dementia Coding, Workup, and Treatment in the VA New England Healthcare System

Growing evidence suggests that Alzheimer’s disease and other types of dementia are underdiagnosed and poorly documented. In our study, we describe patterns of dementia coding and treatment in the Veteran’s Administration New England Healthcare System. We conducted a retrospective cohort study with new outpatient ICD-9 codes for several types of dementia between 2002 and 2009. We examined healthcare utilization, medication use, initial dementia diagnoses, and changes in diagnoses over time by provider type. 8,999 veterans received new dementia diagnoses during the study period. Only 18.3% received a code for cognitive impairment other than dementia, most often “memory loss” (65.2%) prior to dementia diagnosis. Two-thirds of patients received their initial code from a PCP. The etiology of dementia was often never specified by ICD-9 code, even by specialists. Patients followed up exclusively by PCPs had lower rates of neuroimaging and were less likely to receive dementia medication. Emergency room visits and hospitalizations were frequent in all patients but highest in those seen by dementia specialists. Dementia medications are commonly used off-label. Our results suggest that, for the majority the patients, no prodrome of the dementia syndrome is documented with diagnostic code, and patients who do not see dementia specialists have less extensive diagnostic assessment and treatment

Dupilumab Reduces Exacerbations And Improves Lung Function In Children (6-11 Years) With Moderate-To-Severe Asthma And High Eosinophils

Jackson D, Hamelmann E, Roberts G, et al. Dupilumab Reduces Exacerbations And Improves Lung Function In Children (6-11 Years) With Moderate-To-Severe Asthma And High Eosinophils. Journal of Allergy and Clinical Immunology. 2023;151(2):AB194

Impact of dupilumab across seasons in patients with type 2, uncontrolled, moderate-to-severe asthma

Medical writing/editorial assistance was provided by Natalia Crespo, of Excerpta Medica, and was funded by Sanofi and Regeneron Pharmaceuticals Inc., according to the Good Publication Practice guideline s.Background: Seasonal variability could influence asthma exacerbations. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4/IL-13, key and central drivers of type 2 inflammation. In the 52-week QUEST study (NCT02414854), add-on dupilumab every 2 weeks vs placebo significantly reduced exacerbations and improved prebronchodilator forced expiratory volume in 1 second in patients with uncontrolled, moderate-to-severe asthma. TRAVERSE (NCT02134028), the open-label QUEST extension study, enrolled patients with moderate-to-severe asthma to investigate long-term safety and efficacy of dupilumab, including patients who previously received placebo that initiated dupilumab therapy. Objective: To investigate long-term dupilumab efficacy in reducing exacerbations across yearly seasons in patients with type 2 inflammatory asthma with and without clinical evidence of allergic asthma. Methods: Unadjusted annualized exacerbation rate and proportions of patients experiencing severe asthma exacerbations are reported by month and season and for both hemispheres. Results: The proportion of patients with type 2 asthma experiencing 1 or more severe asthma exacerbations during QUEST was 20.8% vs 10.0% in spring, 18.2% vs 7.3% in summer, 22.2% vs 12.6% in autumn, and 26.4% vs 12.0% in winter, for placebo- vs dupilumab-treated patients, respectively; P was less than.001 for placebo vs dupilumab in all seasons. Reductions in the proportion of patients experiencing severe exacerbations across seasons in subgroups with and without evidence of allergic asthma were similar to the overall type 2 population. Reductions in severe exacerbations observed during QUEST were sustained during TRAVERSE, up to 96 weeks across both hemispheres. Conclusion: Dupilumab reduced asthma exacerbations, with no difference in the reduction between seasons, in patients with type 2 inflammation, with and without evidence of allergic asthma

Dupilumab sustains efficacy in patients with moderate-to-severe type 2 asthma regardless of inhaled corticosteroids dose

Background: Dupilumab, a human monoclonal antibody, blocks the shared receptor component for interleukins-4/13, key and central drivers of type 2 inflammation. The TRAVERSE (NCT02134028) open-label extension study demonstrated the long-term safety and efficacy of dupilumab in patients ≥12 years who completed a previous dupilumab asthma study. The safety profile was consistent with that observed in the parent studies. Here, we assess whether dupilumab sustains long-term efficacy in patients regardless of inhaled corticosteroid (ICS) dose at parent study baseline (PSBL). Methods: Patients from phase 2b (NCT01854047) or phase 3 (QUEST; NCT02414854) studies receiving high- or medium-dose ICS at PSBL and enrolled in TRAVERSE were included. We analyzed unadjusted annualized severe exacerbation rates, change from PSBL in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV), 5-item asthma control questionnaire, and type 2 biomarkers in patients with type 2 asthma at baseline (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide [FeNO] ≥25 ppb), and subgroups defined by baseline blood eosinophils or FeNO. Results: Of patients with type 2 asthma (n = 1666), 891 (53.5%) were receiving high-dose ICS at PSBL. In this subgroup, unadjusted exacerbation rates for dupilumab versus placebo were 0.517 versus 1.883 (phase 2b) and 0.571 versus 1.300 (QUEST) over the parent study (52 weeks) and remained low throughout TRAVERSE (0.313-0.494). Improvements in pre-BD FEV were sustained throughout TRAVERSE. Similar clinical efficacy was observed among patients receiving medium-dose ICS at PSBL and biomarker subgroups. Conclusions: Dupilumab showed sustained efficacy for up to 3 years in patients with uncontrolled, moderate-to-severe type 2 asthma on high- or medium-dose ICS