Dose escalation of biologic treatment in patients with moderate-to-severe psoriasis in Japan.

Patients receiving interleukin (IL)-inhibiting biologics for moderate-to-severe psoriasis (PsO) may be treated with escalated doses to optimize outcomes. This study evaluated escalation prevalence in a Japanese claims analysis of patients with PsO diagnosis preceding IL-inhibiting biologic treatment and ≥1 post-induction maintenance claim (index date) with sufficient data availability from January 2014 to May 2022. Patients with non-persistence were excluded. Expected daily dose (EDD) was calculated as the recommended maintenance dose divided by the treatment interval. Dose escalation was defined as ≥2 claims showing a ≥20% increase in the observed average daily dose (ADD) over the EDD (with sensitivities requiring ≥1 claim and ≥30%). Significant differences were tested using multivariable regressions. The study included 982 unique patients treated with brodalumab (BRO; n = 104), guselkumab (GUS; n = 207), ixekizumab (IXE; n = 159), risankizumab (RIS; n = 135), secukinumab (SEC; n = 215) and ustekinumab (UST; n = 196). Within 12 months, dose escalation was observed for all IL-inhibiting biologics other than GUS and RIS: 44.4% for UST, 37.2% for IXE, 3.4% for SEC and 1.4% for BRO. In multivariable-adjusted analyses, odds of dose escalation were significantly lower for all products relative to UST. In sensitivities, escalation was observed for all products except RIS.

Tight control for Crohn's disease with adalimumab-based treatment is cost-effective: an economic assessment of the CALM trial.

OBJECTIVE: To evaluate the cost-effectiveness of an inflammatory biomarker and clinical symptom directed tight control strategy (TC) compared with symptom-based clinical management (CM) in patients with Crohn's disease (CD) naïve to immunosuppressants and biologics using a UK public payer perspective. DESIGN: A regression model estimated weekly CD Activity Index (CDAI)-based transition matrices (remission: CDAI <150, moderate: CDAI ≥150 to <300, severe: CDAI ≥300 to <450, very severe: CDAI ≥450) based on the Effect of Tight Control Management on Crohn's Disease (CALM) trial. A regression predicted hospitalisations. Health utilities and costs were applied to health states. Work productivity was monetised and included in sensitivity analyses. Remission rate, CD-related hospitalisations, adalimumab injections, other direct medical costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. RESULTS: Over 48 weeks, TC was associated with a higher clinical remission (CDAI <150) rate (58.2% vs 46.8%), fewer CD-related hospitalisations (0.124 vs 0.297 events per patient) and more injections of adalimumab (40 mg sc) (mean 31.0 vs 24.7) than CM. TC was associated with 0.032 higher QALYs and £593 higher total medical costs. The ICER was £18 656 per QALY. The ICER was cost-effective in 57.9% of simulations. TC became dominant, meaning less costly but more effective, when work productivity was included. CONCLUSION: A TC strategy as used in the CALM trial is cost-effective compared with CM. Incorporating costs related to work productivity increases the economic value of TC. Cross-national inferences from this analysis should be made with caution given differences in healthcare systems. TRIAL REGISTRATION NUMBER: NCT01235689; Results.

Cost-Effectiveness of Chimeric Antigen Receptor T Cell Therapy in Patients with Relapsed or Refractory Large B Cell Lymphoma: No Impact of Site of Care.

INTRODUCTION: Cost-effectiveness data on chimeric antigen receptor (CAR) T cell therapies for relapsed/refractory large B cell lymphoma (R/R LBCL), accounting for inpatient/outpatient site of care (site), are sparse. METHODS: This payer model compares lifetime costs/benefits for CAR T cell-treated (axicabtagene ciloleucel [axi-cel], lisocabtagene maraleucel [liso-cel], tisagenlecleucel [tisa-cel]) patients with R/R LBCL in the USA. Three-month post-infusion costs were derived from unit costs and real-world all-payer (RW) site-specific utilization data for 1175 patients with diffuse R/R LBCL (CAR T cell therapy October 2017-September 2020). Therapy- and site-specific grade 3+ cytokine release syndrome (CRS) and neurologic event (NE) incidences were imputed from published trials. Lifetime quality-adjusted life-years (QALYs) and long-term costs were calculated from therapy-specific overall and progression-free survival data, adjusted for differences in trial populations. The base case used 17% outpatient site (RW) for all therapies. ZUMA-1 trial cohorts 1/2 informed other axi-cel base case inputs; ZUMA-1 cohorts 4/6 data (updated safety management) supported scenario analyses. RESULTS: Base case total costs for axi-cel exceeded liso-cel ($637 K versus $621 K) and tisa-cel ($631 K versus $577 K) costs. Three-month post-infusion costs were $57 K to $59 K across all therapies. Total QALYs for axi-cel also exceeded those for liso-cel (7.7 versus 5.9) and tisa-cel (7.2 versus 5.0) with incremental costs per QALY gained of $9 K versus liso-cel and $25 K versus tisa-cel. Base case incremental net monetary benefit was $255 K (95% confidence interval (CI) $181-326 K) for axi-cel versus liso-cel, and $280 K (95% CI $200-353 K) versus tisa-cel. Longer survival with axi-cel conferred higher lifetime costs. In all scenarios (e.g., varied outpatient proportions, CRS/NE incidence), axi-cel was cost-effective versus both comparators at a maximum willingness-to-pay of under $26 K/QALY as a result of axi-cel's higher incremental survival gains and quality-of-life. CONCLUSIONS: Axi-cel is a cost-effective CAR T cell therapy for patients with R/R LBCL compared to tisa-cel and liso-cel. Site of care does not impact the cost-effectiveness of CAR T cell therapy.

Estimating Progression Rates Across the Spectrum of Alzheimer's Disease for Amyloid-Positive Individuals Using National Alzheimer's Coordinating Center Data.

INTRODUCTION: Published estimates of Alzheimer's disease (AD) progression do not capture the full disease continuum. This study provides transition probabilities of individuals with amyloid-ß (Aß+) pathology across the disease continuum. METHODS: Patient-level longitudinal data from the National Alzheimer's Coordinating Center were used to estimate progression rates. Progression rates through five clinically defined AD stages-asymptomatic, mild cognitive impairment due to AD (MCI-AD), mild AD dementia, moderate AD dementia, severe AD dementia-and death were measured as transition probabilities. Rates were assessed in "incident" patients who recently entered the stage, controlling for covariates. Transition probabilities were generated from multinomial logit regression models that predicted an individual's health state as a function of health state at the previous visit and adjusted for time between initial and follow-up visits, age, sex, years of education, and concomitant symptomatic AD medications. RESULTS: Annual transition probabilities to more severe dementia stages for surviving incident Aß+ patients were as follows: asymptomatic to MCI-AD, 40.8%; MCI-AD to mild AD dementia or worse, 21.8%; mild AD dementia to moderate AD dementia or worse, 35.9%; moderate AD dementia to severe AD dementia, 28.6%. Transition probabilities to less severe dementia stages were: 5.3% annual reversion from MCI-AD to asymptomatic, 3.0% mild AD dementia to MCI-AD, 1.8% moderate AD dementia to mild AD dementia, and 1.3% for severe AD dementia to moderate AD dementia. CONCLUSIONS: These transition probabilities reflect the full continuum of AD progression in Aß+ individuals and can be used to assess the impact of treatment on expected transitions.

Cost-Utility Analysis of Ravulizumab Compared with Eculizumab in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria, characterized by intravascular hemolysis and venous thrombosis, can be managed with eculizumab, an inhibitor of the complement system; however, patients may periodically experience breakthrough hemolysis. Ravulizumab is a newly approved treatment for paroxysmal nocturnal hemoglobinuria that may reduce breakthrough hemolysis risk, thus improving health-related quality of life and reducing treatment costs. OBJECTIVE: The objective of this study was to compare the costs and benefit of treatment with ravulizumab vs eculizumab in adult patients with paroxysmal nocturnal hemoglobinuria, from a US payer perspective. METHODS: A cost-utility analysis was conducted using a semi-Markov model, informed by clinical experts. Lifetime costs and benefit (quality-adjusted life-years) (both discounted at 3% per annum) and incremental cost-effectiveness ratios were estimated, over a lifetime horizon. Results are reported for an entire treated population and subgroups of eculizumab treatment history. Scenario analyses were characterized by assumptions of non-inferiority between treatments, in terms of breakthrough hemolysis incidence and blood transfusion requirements, and of variations in eculizumab dosing adjustments used in response to breakthrough hemolysis. RESULTS: In the base-case analysis for the overall population, there was a positive impact on health-related quality of life (quality-adjusted life-year gain of 1.67) and costs were lower (- $1,673,465), for ravulizumab vs eculizumab. This led to a negative incremental cost-effectiveness ratio (- $1,000,818, indicating cost savings per quality-adjusted life-year gained). Health-related quality-of-life improvement and cost savings were also observed in all cohorts and scenario analyses. CONCLUSIONS: In adults with paroxysmal nocturnal hemoglobinuria, ravulizumab is associated with improved health-related quality of life and provides a large cost saving from the perspective of a US payer, when compared with eculizumab.

Cost-effectiveness of Voretigene Neparvovec-rzyl vs Standard Care for RPE65-Mediated Inherited Retinal Disease.

IMPORTANCE: Voretigene neparvovec-rzyl, the first gene therapy approved by the US Food and Drug Administration, was approved for the treatment for RPE65-mediated inherited retinal disease (IRD) in December 2017. This gene therapy is associated with high up-front costs and high efficacy, although of unknown duration, and its cost-effectiveness has not been assessed with RPE65 IRD-specific, longitudinal, patient-observation-level data. OBJECTIVE: To assess the incremental cost-effectiveness ratio (ICER) of voretigene neparvovec-rzyl compared with standard care for RPE65-mediated inherited retinal disease. DESIGN, SETTING, AND PARTICIPANTS: In this economic analysis, a health state transition model based on visual acuity and field with a lifetime horizon was developed to estimate the cost-effectiveness of voretigene neparvovec-rzyl. The model was populated with data from a clinical trial of voretigene neparvovec-rzyl to evaluate treatment outcome and a natural history study of RPE65-mediated IRD to examine disease progression. Direct costs were derived from the literature. Indirect costs, including educational attainment, productivity, caregiver burden, and governmental programs, were estimated using published literature and data analysis of public national surveys. A health utility vignette study specific to RPE65-mediated IRD was used for health utility inputs. The cost-effectiveness study described in this article was conducted from September 15, 2017, to August 23, 2018. EXPOSURES: Bilateral voretigene neparvovec-rzyl therapy or standard care. MAIN OUTCOMES AND MEASURES: Incremental cost-effectiveness ratio. RESULTS: The model population included 70 patients with RPE65-mediated IRD, with a mean age of 15 years; 42 of 70 patients (60%) were female. In the base case, voretigene neparvovec-rzyl compared with standard care was associated with lower total costs ($2.2 million vs $2.8 million) and higher quality-adjusted life-years (18.1 vs 8.6). Voretigene neparvovec-rzyl remains cost-effective if at least 8.8% of the long-term treatment effect continues after year 3 when including indirect costs and 43.3% when excluding indirect costs, assuming a cost threshold of $150 000 per quality-adjusted life-year. CONCLUSIONS AND RELEVANCE: Results of this study suggest that voretigene neparvovec-rzyl is cost-effective compared with standard care when using a lifetime horizon, excluding indirect costs, and using a threshold of $150 000 per quality-adjusted life-year.

Estimation of impact of RPE65-mediated inherited retinal disease on quality of life and the potential benefits of gene therapy.

BACKGROUND/AIMS: In rare diseases, health-related quality of life (HRQL) data can be difficult to capture. Given the ultrarare nature of RPE65-mediated inherited retinal disease (IRD), it was not feasible to recruit a patient sample and collect HRQL data prospectively. The objectives of this study were to develop health state descriptions of RPE65-mediated IRD, and to estimate associated patient utilities. METHODS: Vignette descriptions of IRD states were developed and then assessed to elicit utilities. The vignettes ranged from moderate vision loss through to hand motion to no light perception (NLP). Six retina specialists with additional expertise in IRDs provided a proxy valuation of the vignettes using generic measures of health-the 5-level version of EQ-5D-5L and Health Utility Index 3 (HUI3). The data were then scored using standard methods for each instrument. RESULTS: Weights from both HRQL measures revealed a large decline in scores with vision loss. The EQ-5D-5L weights ranged from 0.709 for moderate vision loss to 0.152 for hand motion to NLP. The HUI3 weights ranged from 0.519 to - 0.039, respectively. A decline was seen on both measures, and the degree of decline from moderate vision loss to NLP was identical on both (-0.56). CONCLUSION: This is the first study to report HRQL weights (or utilities) for health states describing different levels of vision loss in patients with IRD, specifically those with RPE65-mediated disease. The parallel decline in scores from the EQ-5D and HUI3 corroborates the substantial impact of progressive vision loss on HRQL.

The Impact of Contract Operations on Safety in Underground Coal Mines.

OBJECTIVE: The aim of this study was to test for differences in injury rates for contractor-operated underground coal mines relative to owner-operated mines in Kentucky, controlling for other covariates. METHODS: We used disparities between MSHA contractor data and surface reclamation permit data to identify mines operated by contractors. We then used negative binomial regression to estimate injury rates from 1999 to 2013, controlling for mine and controller characteristics available from MSHA and the Energy Information Administration (EIA). RESULTS: Contractor-operated mines with 15 or fewer full-time equivalent workers (FTEs) had a statistically significant 57% higher covariate-adjusted reported traumatic injury rate than similar mines without contract operators. Larger contractor-operated mines did not have a statistically significant elevated rate. CONCLUSIONS: We detected a significant elevation of traumatic injury rates only among the smallest contractor-operated mines. This increase appears substantial enough to warrant attention.

The impact of bariatric surgery on comorbidities and medication use among obese patients.

BACKGROUND: The risks and benefits of bariatric surgery have rarely been evaluated in large multiyear patient samples. This study identifies the short- and long-term impact of bariatric surgery on comorbidities and medication use among obese patients. METHODS: A comprehensive analysis of 5,502 obese patients who underwent bariatric surgery was performed. Submissions of reimbursement claims, including diagnostics and medication use, were compared in the 90 days preceding the surgery and 30 up to 1,110 days following the surgery. Presurgery and postsurgery frequency counts were performed on diagnostics and medication use to identify trends. RESULTS: Among 5,502 patients, significant decreases in the prevalence of reported comorbidities were observed during the short-term postsurgery period and sustained for up to 3 years of follow-up. Compared to the presurgery period, significant decreases (p < 0.05) were observed after 3 years for total cardiovascular disorders (43.6% vs. 14.2%), diabetes mellitus (19.9% vs. 7.7%), chronic obstructive pulmonary disease and other respiratory conditions (57.7% vs. 16.2%), diseases of the musculoskeletal system and connective tissue (32.6% vs. 27.7%), and mental disorders (30.7% vs. 14.8%). Over the same period, the frequency of medication use decreased significantly for a number of conditions including infections, pain, respiratory, cardiovascular, gastroenterologic, lipidemic, and diabetic conditions. Anemia, however, increased from 3.8% to 9.9%, and use of nutritional supplements increased significantly. CONCLUSION: Bariatric surgery was associated with significant reductions in reported claims for short- and long-term health outcomes and reduced medication use for major disease categories.

A study on the economic impact of bariatric surgery.

OBJECTIVE: To evaluate the private third-party payer return on investment for bariatric surgery the United States. STUDY DESIGN: Morbidly obese patients aged 18 years or older were identified in an employer claims database of more than 5 million beneficiaries (1999-2005) using International Classification of Diseases, Ninth Revision, Clinical Modification code 278.01. Each of 3651 patients who underwent bariatric surgery during this period was matched to a control subject who was morbidly obese and never underwent bariatric surgery. Bariatric surgery patients and controls were matched based on patient demographics, selected comorbidities, and costs. METHODS: Total healthcare costs for bariatric surgery patients and their controls were recorded for 6 months before surgery through the end their continuous enrollment. To account for potential differences in patient characteristics, we calculated the cost differential by estimating a Tobit model. A return on investment was estimated from the resulting coefficients. Costs were inflation adjusted to 2005 US dollars using the Consumer Price Index for Medical Care, and the cost savings were discounted by 3.07%, the month Treasury bill rate during the same period. RESULTS: The mean bariatric surgery investment ranged from approximately $17,000 to $26,000. After controlling for observable patient characteristics, we estimated all costs to have been recouped within 2 years for laparoscopic surgery patients and within 4 years for open surgery patients. CONCLUSIONS: Downstream savings associated with bariatric surgery are estimated to offset the initial costs in 2 to 4 years. Randomized or quasiexperimental studies would be useful to confirm this conclusion, as unobserved characteristics may influence the decision to undergo surgery and cannot be controlled for in this analysis.