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Objectives: To investigate psychometric performance of the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) total and individual item scores in patients with psoriatic arthritis (PsA) and to estimate score change thresholds and scores corresponding to different levels of symptom/impact severity., Methods: Data up to week 16 from 1252 patients with active PsA enrolled in two randomised controlled trials of bimekizumab (BE OPTIMAL (NCT03895203) and BE COMPLETE (NCT03896581)) were used to assess construct validity (correlations with other patient-reported outcomes), known-groups validity (based on Minimal Disease Activity index, Disease Activity Index for Psoriatic Arthritis and Psoriatic Arthritis Disease Activity Score), reliability (Cronbach's alpha and intraclass correlation coefficients (ICCs)) and responsiveness (sensitivity to change). Clinically meaningful within-patient improvement thresholds were estimated by anchor-based and distribution-based analyses, and symptom/impact severity thresholds were estimated by receiver operating characteristic curve analyses., Results: The mean (SD) PsAID-12 total score at baseline was 4.19 (1.94). PsAID-12 scores demonstrated good convergent validity and good known-groups validity. Internal consistency reliability (Cronbach's alpha 0.95) and test-retest reliability (ICC ≥ 0.70) were also good. Responsiveness was acceptable (correlations ≥0.30 for most scores). Improvement thresholds were estimated at 1.5-2 points for the PsAID-12 total score and 2 or 3 points for item scores. Thresholds for different levels of symptom/impact severity could be derived for most PsAID-12 items., Conclusions: The PsAID-12 demonstrated robust psychometric properties in a large sample of patients with active PsA, supporting its use as a fit-for-purpose patient-reported outcome in this population. Furthermore, thresholds for score interpretation were derived., Competing Interests: Competing interests: LG: Grants from AbbVie, Biogen, Eli Lilly, Novartis, Sandoz and UCB Pharma; consulting fees from AbbVie, Amgen, BMS, Celltrion, Galapagos, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Sandoz and UCB Pharma. A-MO: Research grants to Johns Hopkins University from AbbVie, Amgen and Janssen; consulting fees from BMS, Janssen, Sanofi and UCB Pharma. LCC: Grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB Pharma; consultant for AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Galapagos, Gilead, Janssen, Moonlake Pharma, Novartis, Pfizer, and UCB Pharma; speaking fees from AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, medac, Novartis, Pfizer, and UCB Pharma. DG: Consultant and/or received grant support from Abbvie, Amgen, BMS, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, and UCB Pharma. AO: Grant/research support from AbbVie, Amgen, Janssen, Novartis and Pfizer, consultant of AbbVie, Amgen, BMS, Celgene, CorEvitas, Eli Lilly, GSK, Gilead, Janssen, Novartis, Pfizer, Takeda and UCB Pharma. CGP: Employed by Evidera, a part of Thermo Fisher Scientific, which received funding for this research from UCB Pharma. VC, VT and JL: Employees and stockholders of UCB Pharma. BI: Employee of UCB Pharma; shareholder of AbbVie, GlaxoSmithKline and UCB Pharma. MdW: Over the last five years Stichting Tools has received fees for lectures or consultancy provided by MdW from Celgene, Eli Lilly, Janssen-Cilag, Pfizer and UCB Pharma., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Cystic fibrosis (CF) is a rare genetic disease characterized by life-shortening lung function decline. Ivacaftor, a CF transmembrane conductance regulator modulator (CFTRm), was approved in 2012 for people with CF with specific gene mutations. We used real-world evidence of 5-year mortality impacts of ivacaftor in a US registry population to validate a CF disease-progression model that estimates the impact of ivacaftor on survival., Methods: The model projects the impact of ivacaftor vs. standard care in people with CF aged ≥6 years with CFTR gating mutations by combining parametric equations fitted to historical registry survival data, with mortality hazards adjusted for fixed and time-varying person-level characteristics. Disease progression with standard care was derived from published registry studies and the expected impact of ivacaftor on clinical characteristics was derived from clinical trials. Individual-level baseline characteristics of the registry ivacaftor-treated population were entered into the model; 5-year model-projected mortality with credible intervals (CrIs) was compared with registry mortality to evaluate the model's validity., Results: Post-calibration 5-year mortality projections closely approximated registry mortality in populations treated with standard care (6.4% modeled [95% CrI: 5.3% to 7.6%] vs. 6.0% observed) and ivacaftor (3.4% modeled [95% CrI: 2.7% to 4.4%] vs. 3.1% observed). The model accurately predicted 5-year relative risk of mortality (0.53 modeled [0.47 to 0.60] vs. 0.51 observed) in people treated with ivacaftor vs. standard care., Conclusions: Modeled 5-year survival projections for people with CF initiating ivacaftor vs. standard care align closely with real-world registry data. Findings support the validity of modeling CF to predict long-term survival and estimate clinical and economic outcomes of CFTRm., Competing Interests: All authors received nonfinancial support from ArticulateScience LLC (editorial assistance) and Complete HealthVizion, IPG Health Medical Communications (project management and editing support), which both received funding from Vertex Pharmaceuticals Incorporated. Additional disclosures are as follows: Lisa J. McGarry, Zahra Bhaiwala, Andrea Lopez, and Jaime L. Rubin are employees of Vertex Pharmaceuticals Incorporated and may own stock or stock options in that company; in addition, Zahra Bhaiwala reports consulting fees from Evidera. Conor Chandler and Christopher G. Pelligra are employed by Evidera, an independent research company that provides consulting and other research services to pharmaceutical, medical device, and related organizations; in their salaried positions, they work with a variety of companies and are precluded from receiving payment or honoraria directly from these organizations for services rendered. Evidera received payment from Vertex Pharmaceuticals Incorporated for the conduct of this study. Theodore G. Liou, MD, is an employee of the University of Utah and is supported by the NIH/NHLBI (R01 HL125520), the Cystic Fibrosis Foundation, Bethesda, MD (grants CC-132-16AD, LIOU13A0, LIOU14Y0, and LIOU14Y4), the Ben B. and Iris M. Margolis Family Foundation of Utah, and the Claudia Ruth Goodrich Stevens Endowment Fund. The target data used for model validation included patients treated with ivacaftor, which is manufactured by Vertex Pharmaceuticals Incorporated. This does not alter our adherence to PLOS ONE policies on sharing data and materials" and added to the Financial Disclosure statement., (Copyright: © 2023 McGarry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: For patients with lower-risk (LR) myelodysplastic syndromes (MDS), overall survival (OS) is rarely a primary clinical trial endpoint. Treatments such as lenalidomide can reduce red blood cell (RBC) transfusion burden (TB) and serum ferritin, but the long-term impact on OS remains undetermined., Patients and Methods: Data from 3 trials evaluating lenalidomide in patients with LR-MDS (the phase 2 MDS-003 and phase 3 MDS-004 trials in del[5q]; the phase 3 trial MDS-005 in non-del[5q] patients) were pooled. Predictors of OS were assessed by multivariate analysis using time-dependent models for TB and RBC transfusion independence (RBC-TI), and a landmark analysis of RBC-TI at 17 weeks. Separate analyses using MDS-004 and MDS-005 data determined the relationship between OS and serum ferritin., Results: Median follow-up for MDS-003, MDS-004, and MDS-005 was 3.2, 3.0, and 1.7 years, respectively. In multivariate analyses, transfusion of ≥6 RBC units over 8 weeks was a significant predictor of shorter OS vs. 0 units in the time-dependent TB model (hazard ratio [HR] 4.65; 95% confidence interval [CI] 3.32-6.52; P < .0001). RBC-TI achievement was associated with prolonged OS in the time-dependent (HR 0.48; 95% CI 0.37-0.62; P < .0001) and landmark model (HR 0.57; 95% CI 0.44-0.75; P < .0001). Increased serum ferritin was associated with shorter OS (P < .0001)., Conclusion: This analysis of prospective trial data in patients with LR-MDS confirms lenalidomide may improve OS by reducing TB and serum ferritin. OS should be considered as an endpoint in future lower risk MDS clinical trials., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Pomalidomide plus low-dose dexamethasone (POM-d), daratumumab monotherapy (DARA), and carfilzomib monotherapy (CAR) have been approved for use in the treatment of patients with heavily pretreated relapsed-refractory multiple myeloma (RRMM) in the US, based on findings from the MM-002, SIRIUS, and PX-171-003-A1 studies, respectively. The objective of this study was to assess the cost-effectiveness of POM-d, DARA, and CAR in this patient population from a US payer's perspective., Methods: A cost-effectiveness model was developed to estimate the cost and health outcomes over a 3-year time horizon in 3 health states: progression-free, post-progression, and death. The main efficacy data source was a matching-adjusted indirect comparison using data from the aforementioned studies. Direct medical costs were considered, including: treatment acquisition and administration (initial line and subsequent line), pre- and post-medication, prophylaxis treatment, adverse event management, and health care resource utilization. Sensitivity analyses were conducted. A scenario analysis that assumed equal efficacy across all 3 treatments was conducted. Costs, life-years, and quality-adjusted life-years were estimated and discounted at 3% per annum., Findings: Over 3 years, the use of POM-d was associated with similar life-years and quality-adjusted life-years gained compared with DARA and CAR (incremental: life-years, +0.02 and +0.07, respectively; quality-adjusted life-years, +0.01 and +0.05), and with a cost less than that of DARA (-$8,919) and similar to that of CAR (-$195). Sensitivity analyses illustrated that the results were sensitive to progression-free survival, treatment duration, and drug costs. An equal efficacy scenario resulted in cost-savings relative to those of both DARA and CAR (-$11,779 and -$12,595)., Implications: POM-d may be a cost-effective treatment option relative to DARA or CAR in heavily pretreated patients with RRMM in the US., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To conduct a cost-effectiveness assessment of lenalidomide plus dexamethasone (Rd) vs bortezomib plus melphalan and prednisone (VMP) as initial treatment for transplant-ineligible patients with newly-diagnosed multiple myeloma (MM), from a U.S. payer perspective., Methods: A partitioned survival model was developed to estimate expected life-years (LYs), quality-adjusted LYs (QALYs), direct costs and incremental costs per QALY and LY gained associated with use of Rd vs VMP over a patient's lifetime. Information on the efficacy and safety of Rd and VMP was based on data from multinational phase III clinical trials and a network meta-analysis. Pre-progression direct costs included the costs of Rd and VMP, treatment of adverse events (including prophylaxis) and routine care and monitoring associated with MM. Post-progression direct costs included costs of subsequent treatment(s) and routine care and monitoring for progressive disease, all obtained from published literature and estimated from a U.S. payer perspective. Utilities were obtained from the aforementioned trials. Costs and outcomes were discounted at 3% annually., Results: Relative to VMP, use of Rd was expected to result in an additional 2.22 LYs and 1.47 QALYs (discounted). Patients initiated with Rd were expected to incur an additional $78,977 in mean lifetime direct costs (discounted) vs those initiated with VMP. The incremental costs per QALY and per LY gained with Rd vs VMP were $53,826 and $35,552, respectively. In sensitivity analyses, results were found to be most sensitive to differences in survival associated with Rd vs VMP, the cost of lenalidomide and the discount rate applied to effectiveness outcomes., Conclusions: Rd was expected to result in greater LYs and QALYs compared with VMP, with similar overall costs per LY for each regimen. Results of this analysis indicated that Rd may be a cost-effective alternative to VMP as initial treatment for transplant-ineligible patients with MM, with an incremental cost-effectiveness ratio well within the levels for recent advancements in oncology.

Objective: The economic implications from the US Medicare perspective of adopting alternative treatment strategies for acute bacterial skin and skin structure infections (ABSSSIs) are substantial. The objective of this study is to describe a modeling framework that explores the impact of decisions related to both the location of care and switching to different antibiotics at discharge., Methods: A discrete event simulation (DES) was developed to model the treatment pathway of each patient through various locations (emergency department [ED], inpatient, and outpatient) and the treatments prescribed (empiric antibiotic, switching to a different antibiotic at discharge, or a second antibiotic). Costs are reported in 2012 USD., Results: The mean number of days on antibiotic in a cohort assigned to a full course of vancomycin was 11.2 days, with 64% of the treatment course being administered in the outpatient setting. Mean total costs per patient were $8671, with inpatient care accounting for 58% of the costs accrued. The majority of outpatient costs were associated with parenteral administration rather than drug acquisition or monitoring. Scenarios modifying the treatment pathway to increase the proportion of patients receiving the first dose in the ED, and then managing them in the outpatient setting or prescribing an oral antibiotic at discharge to avoid the cost associated with administering parenteral therapy, therefore have a major impact and lower the typical cost per patient by 11-20%. Since vancomycin is commonly used as empiric therapy in clinical practice, based on these analyses, a shift in treatment practice could result in substantial savings from the Medicare perspective., Conclusions: The choice of antibiotic and location of care influence the costs and resource use associated with the management of ABSSSIs. The DES framework presented here can provide insight into the potential economic implications of decisions that modify the treatment pathway.