Health-related quality of life with sacituzumab govitecan in HR+/HER2- metastatic breast cancer in the phase III TROPiCS-02 trial.

BACKGROUND: The TROPiCS-02 study (NCT03901339) demonstrated that sacituzumab govitecan (SG) has superior clinical outcomes over treatment of physician's choice (TPC) chemotherapy in patients with hormone receptor-positive, human epidermal growth factor 2 receptor-negative (HR+/HER2-) metastatic breast cancer (mBC). Here, we present health-related quality of life (HRQoL) patient-reported outcome (PRO) findings from this study. PATIENTS AND METHODS: Eligible adults with HR+/HER2- mBC who previously received a taxane, endocrine-based therapy, a CDK4/6 inhibitor, and 2-4 lines of chemotherapy were randomized 1:1 to receive SG or TPC until progression or unacceptable toxicity. PROs were assessed at baseline and on day 1 of each cycle, using the European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 (EORTC QLQ-C30), EQ-5D-5L, and PRO Common Terminology Criteria for Adverse Events (PRO-CTCAE). RESULTS: Compared to TPC, overall least square mean change from baseline was significantly better for SG for physical functioning and dyspnea, but worse for diarrhea. Time to first clinically meaningful worsening or death was significantly longer for SG in global health status/quality of life, physical functioning, fatigue, emotional functioning, dyspnea, insomnia, and financial difficulties of the EORTC QLQ-C30 and the EQ-VAS, but longer for TPC in diarrhea. Few patients in both arms reported experiencing any worsening to level 3 or 4 treatment-related symptomatic events during treatment, as assessed by 16 PRO-CTCAE items, except for diarrhea frequency and amount of hair loss, which favored TPC. CONCLUSIONS: SG was associated with an HRQoL benefit in most symptoms and functioning, compared with TPC. This supports the favorable profile of SG as a treatment option for patients with pretreated HR+/HER2- mBC.

Health-related quality of life in the phase III ASCENT trial of sacituzumab govitecan versus standard chemotherapy in metastatic triple-negative breast cancer.

BACKGROUND: The antibody-drug conjugate sacituzumab govitecan (SG) prolongs progression-free survival and overall survival in patients with refractory/relapsed metastatic triple-negative breast cancer (mTNBC). Here, we investigated its effect on health-related quality of life (HRQoL). METHODS: This analysis was based on the open-label phase III ASCENT trial (NCT02574455). Adults with refractory/relapsed mTNBC who had received ≥2 prior systemic therapies (≥1 in the metastatic setting) were randomised 1:1 to SG or treatment of physician's choice (TPC; capecitabine, eribulin, vinorelbine, or gemcitabine). HRQoL was assessed on day 1 of each treatment cycle using the EORTC QLQ-C30. Score changes from baseline were analysed using linear mixed-effect models for repeated measures. Stratified Cox regressions evaluated time to first clinically meaningful change of HRQoL. RESULTS: The analysis population comprised 236 patients randomised to SG and 183 to TPC. For global health status (GHS)/QoL, physical functioning, fatigue, and pain, changes from baseline were superior for SG versus TPC. Compared with TPC, SG was inferior regarding changes from baseline for nausea/vomiting and diarrhoea but non-inferior for other QLQ-C30 domains. Median time to first clinically meaningful worsening was longer for SG than for TPC for physical functioning (22.1 versus 12.1 weeks, P < 0.001), role functioning (11.4 versus 7.1 weeks, P < 0.001), fatigue (7.7 versus 6.0 weeks, P < 0.05), and pain (21.6 versus 9.9 weeks, P < 0.001). CONCLUSIONS: SG was generally associated with greater improvements and delayed worsening of HRQoL scores compared with TPC. This supports the favourable profile of SG as an mTNBC treatment.

Treatment patterns in rheumatoid arthritis patients newly initiated on biologic and conventional synthetic disease-modifying antirheumatic drug therapy and enrolled in a North American clinical registry.

BACKGROUND: Understanding the evolving treatment patterns in patients with rheumatoid arthritis (RA) is important for rheumatologists to make the best practice decisions and optimize treatment. Here, we describe treatment patterns among patients newly initiated on biologic and/or nonbiologic RA therapy over time after enrollment in the US Corrona RA registry. METHODS: This was a retrospective, cohort study of adult patients with RA enrolled in the Corrona RA registry. Patients were included in this study if they initiated therapy with conventional synthetic disease-modifying antirheumatic drug (csDMARD) monotherapy, TNF inhibitor (TNFi) monotherapy, other (non-TNFi) biologic monotherapy, or combination therapy (index therapy); initiated therapy between January 1, 2004, and December 31, 2015 (index date), after enrollment in the Corrona RA registry; had at least 6 months of follow-up time after the index date; and had at least one follow-up visit. Time periods of interest were based on the year of index therapy initiation: 2004-2007, 2008-2011, and 2012-2015. RESULTS: This study included 8027 patients. csDMARD monotherapy and TNFi + csDMARD combination therapy were the most common index therapies in the registry (39.9% and 44.9%, respectively, in the 2004-2007 period; 38.6% and 38.2%, respectively, in the 2008-2011 period; and 35.2% for both in the 2012-2015 period). At therapy initiation, a higher proportion of patients who initiated other biologics, whether as monotherapies (54.0%) or in combination with csDMARD (49.9%), had high disease activity than those who initiated csDMARD monotherapy (28.4%). For 2012-2015 vs 2004-2007 and 2008-2011 periods, persistence on a given therapy appeared to decrease for the TNFi monotherapy cohort (48.2% vs 64.3% and 52.4%) and other biologic monotherapy cohort (52.3% vs 71.4% and 54.5%) over 12 months; switching from one therapy to another was common in the Corrona RA registry. CONCLUSIONS: Increased switching from one therapy to another and decreased time on a given therapy was observed in the Corrona RA registry in the 2012-2015 period. This observation is most likely due to the increased availability of additional treatment options and/or the change in clinical focus, particularly the emphasis on achievement of treat-to-target goals of remission or low disease activity along with more aggressive treatment.

Ex Ante Economic Evaluation of Arg389 Genetically Targeted Treatment with Bucindolol versus Empirical Treatment with Carvedilol in NYHA III/IV Heart Failure.

OBJECTIVE: The Beta-Blocker Evaluation Survival Trial showed no survival benefit for bucindolol in New York Heart Association (NYHA) class III/IV heart failure (HF) with reduced ejection fraction, but subanalyses suggested survival benefits for non-Black subjects and Arg389 homozygotes. We conducted an ex ante economic evaluation of Arg389 targeted treatment with bucindolol versus carvidolol, complementing a previous ex ante economic evaluation of bucindolol preceded by genetic testing for the Arg389 polymorphism, in which genetic testing prevailed economically over no testing. METHODS: A decision tree analysis with an 18-month time horizon was performed to estimate the cost effectiveness/cost utility of trajectories of 100%, 50%, and 0% of patients genetically tested for Arg389 and comparing bucindolol with empirical carvedilol treatment as per prior BEST subanalyses. Incremental cost-effectiveness/cost-utility ratios (ICERs/ICURs) were estimated. RESULTS: Race-based analyses for non-White subjects at 100% testing showed a loss of (0.04) life-years and (0.03) quality-adjusted life-years (QALYs) at an incremental cost of $2185, yielding a negative ICER of ($54,625)/life-year and ICUR of ($72,833)/QALY lost; at 50%, the analyses showed a loss of (0.27) life-years and (0.16) QALYs at an incremental cost of $1843, yielding a negative ICER of ($6826)/life-year and ICUR of ($11,519)/QALY lost; at 0%, the analyses showed a loss of (0.33) life-years and (0.30) QALYs at an incremental cost of $1459, yielding a negative ICER of ($4421)/life-year and ICUR of ($4863)/QALY lost. Arg389 homozygote analyses at 100% testing showed incremental gains of 0.02 life-years and 0.02 QALYs at an incremental cost of $378, yielding an ICER of 18,900/life-year and ICUR of $18,900/QALY gained; at 50%, the analyses showed a loss of (0.24) life-years and (0.09) QALYs at an incremental cost of $1039, yielding a negative ICER of ($4329)/life-year and ICUR of ($9336)/QALY lost; at 0%, the analyses showed a loss of (0.33) life-years and (0.30) QALYs at an incremental cost of $1459, yielding a negative ICER of ($4421)/life-year and ICUR of ($4863)/QALY lost. CONCLUSION: This independent ex ante economic evaluation suggests that genetically targeted treatment with bucindolol is unlikely to yield clinicoeconomic benefits over empirical treatment with carvedilol in NYHA III/IV HF.

The Effect of Dose Escalation on the Cost-Effectiveness of Etanercept and Adalimumab with Methotrexate Among Patients with Moderate to Severe Rheumatoid Arthritis.

BACKGROUND: Patients with moderate to severe rheumatoid arthritis (RA) occasionally increase their doses of tumor necrosis factor (TNF) inhibitors, especially the monoclonal antibody origin drugs such as adalimumab and infliximab, after inadequate response to the initial dose. Previous studies have evaluated the cost-effectiveness of various sequences of treatment for RA in the United States but have not considered the effect of dose escalation. OBJECTIVE: To assess the cost-effectiveness of etanercept and adalimumab by incorporating the effect of dose escalation in moderate to severe RA patients. METHODS: We adapted the open-source Innovation and Value Initiative - Rheumatoid Arthritis model, version 1.0 to separately simulate the magnitude and time to dose escalation among RA patients taking adalimumab plus methotrexate or etanercept plus methotrexate from a societal perspective and lifetime horizon. An important assumption in the model was that dose escalation would increase treatment costs through its effect on the number of doses but would have no effect on effectiveness. We estimated the dose escalation parameters using the IBM MarketScan Commercial and Medicare Supplemental Databases. We fit competing parametric survival models to model time to dose escalation and used model diagnostics to compare the fit of the competing models. We measured the magnitude of dose escalation as the percentage increase in the number of doses conditional on dose escalation. Finally, we used the parameterized model to simulate treatment sequences beginning with a TNF inhibitor (adalimumab, etanercept) followed by nonbiologic treatment. RESULTS: In baseline models without dose escalation, the incremental cost per quality-adjusted life-year of the etanercept treatment sequence relative to the adalimumab treatment sequence was $85,593. Incorporating dose escalation increased treatment costs for each sequence, but costs increased more with adalimumab, lowering the incremental cost-effectiveness ratio to $9,001. At willingness-to-pay levels of $100,000, the etanercept sequence was more cost-effective compared with the adalimumab sequence, with probability 0.55 and 0.85 in models with and without dose escalation, respectively. CONCLUSIONS: Dose escalation has important effects on cost-effectiveness and should be considered when comparing biologic medications for the treatment of RA. DISCLOSURES: Funding for this study was contributed by Amgen. When this work was conducted, Incerti and Jansen were employees of Precision Health Economics, which received financial support from Amgen. Maksabedian Hernandez, Collier, Gharaibeh, and Stolshek were employees and stockholders of Amgen, and Tkacz and Moore-Schiltz were employees of IBM Watson Health, which received financial support from Amgen. Some of the results of this work were previously presented as a poster at the 2019 AMCP Managed Care & Specialty Pharmacy Annual Meeting, March 25-28, 2019, in San Diego, CA.

Effectiveness and Costs Among Rheumatoid Arthritis Patients Treated with Targeted Immunomodulators Using Real-World U.S. Data.

BACKGROUND: Targeted immunomodulators (TIMs) are used for the treatment of moderate to severe rheumatoid arthritis (RA) and include biologic and nonbiologic medications with different mechanisms of action. Data describing disease activity levels in RA are not directly available in claims databases but can be determined using a claims-based effectiveness algorithm. Rheumatology has benefited from the recent introduction of new drugs, many with new mechanisms of action. We provide an analysis of this broader range of medications. OBJECTIVES: To (a) describe and summarize the effectiveness of available TIMs for the treatment of moderate to severe RA and (b) determine the RA-related health care costs per effectively treated patient, using recent data. METHODS: This was a retrospective analysis using data from the IBM MarketScan Commercial Claims and Encounters Database from July 1, 2012, through December 31, 2016. Index date was the new prescription claim for a TIM (abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, tocilizumab, or tofacitinib). A 6-month pre-index baseline period was used to determine demographic and clinical characteristics. Patients without a TIM claim during the baseline period were considered naive; patients with a TIM claim in the baseline period that was different than the index TIM were assessed as receiving second-line therapy. A claims-based algorithm was used to assess 12-month treatment effectiveness and total RA-related costs. Costs included RA-related pharmacy costs and medical costs. RESULTS: Data from 14,775 patients were analyzed, including patients prescribed abatacept (n = 1,250), adalimumab (n = 4,986), certolizumab pegol (n = 387), etanercept (n = 5,266), golimumab (n = 577), infliximab (n = 969), tocilizumab (n = 451), and tofacitinib (n = 889). Of these, 705 were receiving second-line therapy. TIM effectiveness by first-line and second-line therapy, respectively, were abatacept 27.1%, 18.1%; adalimumab 30.9%, 22.1%; certolizumab pegol 20.9%, 14.3%; etanercept 31.4%, 31.5%; golimumab 32.7%, 22.2%; infliximab 21.9%, 21.3%; tocilizumab 30.9%, 30.6%; and tofacitinib 26.0%, 21.6%. The main reason for failing effectiveness was not achieving an 80% medication possession ratio or being nonadherent. The 1-year total RA-related cost per effectively treated patient for first-line and second-line therapies, respectively, were abatacept $121,835, $174,090; adalimumab $112,708, $154,540; certolizumab pegol $149,946, $236,743; etanercept $102,058, $94,821; golimumab $108,802, $140,651; infliximab $155,123, $185,369; tocilizumab $93,333, $109,351; and tofacitinib $100,306, $130,501. CONCLUSIONS: The effectiveness of TIMs from this real-world experience showed that the range of patients who were effectively treated with first-line therapy was higher for certain tumor necrosis factor inhibitors and tocilizumab. The percentages of effectively treated patients were generally lower in second-line treatment compared with first-line except for etanercept, which had the same percentage between lines of therapy. Etanercept had the lowest RA-related cost per effectively treated patient among tumor necrosis factor inhibitors in first-line use and the lowest RA-related cost per effectively treated patient compared with all second-line treatments. DISCLOSURES: This study was sponsored by Amgen. Amgen employees contributed to study design, analysis of the data, and the decision to publish the results. Maksabedian Hernandez and Stolshek are employees and shareholders of Amgen; Gharaibeh was employed by Amgen at the time of this study. Bonafede was employed by IBM Watson Health, at the time of this study, and McMorrow is employed by IBM Watson Health, which received funding from Amgen to conduct this study. Data from this study were presented at AMCP Nexus, October 22-25, 2018, in Orlando, FL.

Treatment Patterns and Costs in Biologic DMARD-Naive Patients with Rheumatoid Arthritis Initiating Etanercept or Adalimumab with or Without Methotrexate.

BACKGROUND: Etanercept (ETN) and adalimumab (ADA) are tumor necrosis factor inhibitors indicated for treatment of moderate to severe rheumatoid arthritis (RA) and are used as monotherapy or in combination with conventional disease-modifying antirheumatic drugs (DMARDs) such as methotrexate (MTX). Data on treatment patterns and costs of ETN and ADA as monotherapies or in combination therapy with MTX are lacking in biologic DMARD (bDMARD)-naive patients with RA. OBJECTIVE: To evaluate treatment patterns and costs of ETN and ADA monotherapy and combination therapy in bDMARD-naive patients with RA. METHODS: Data from adult bDMARD-naive patients with RA were evaluated according to index therapy (ADA or ETN as monotherapy or combination therapy with MTX) in a retrospective cohort study using the IBM MarketScan Commercial Claims and Encounters and Medicare Supplemental Databases from January 1, 2010, to June 30, 2017. Participants were bDMARD-naive for ≥ 12 months before initial ETN or ADA pharmacy claim (index date) and had continuous enrollment for ≥ 12 months pre-index and 24 months post-index. Combination therapy cohorts had an MTX claim within 30 days of the index date. Outcomes included persistence (no treatment changes or gap [≥ 60 days]); modifications to index therapy (discontinuation or switching without prior gap, restarting as switch or restart after gap, or MTX initiation/discontinuation); and mean total bDMARD costs for 2 years post-index. RESULTS: Patients on ETN monotherapy (n = 2,064) had higher persistence (26.8% vs. 21.1%, respectively; P < 0.001) on index treatment and received treatment for a longer duration (mean 375.9 days vs. 339.7 days, respectively; P < 0.001) than those on ADA monotherapy (n = 1,528). Regimen changes were more common in patients on ADA monotherapy than patients on ETN monotherapy (38.0% vs. 33.4%, respectively; P = 0.004). More patients on ADA monotherapy added MTX than those on ETN (17.5% vs. 12.6%, respectively; P < 0.001). Overall, 790 patients receiving index monotherapy had a regimen change following a gap (≥ 60 days), with a similar proportion between cohorts. Among these patients, 13.8% restarted index therapy, and 7.9% switched from index therapy. Significantly more patients receiving ETN monotherapy restarted their index regimen after a gap than those receiving ADA monotherapy (14.9% vs. 12.2%, respectively; P = 0.023). The proportion of patients persistent on combination therapy was similar between the ETN and ADA combination therapy cohorts (21.9% vs. 22.2%, respectively; P = 0.818). Treatment pattern rates were similar regardless of index combination therapy. Overall, costs for ADA were consistently higher within the index regimen throughout the follow-up period irrespective of MTX. CONCLUSIONS: ETN monotherapy as first-line treatment was associated with higher persistence, lower rate of MTX supplementation, and lower bDMARD costs than ADA monotherapy. ETN monotherapy may represent a less costly option for achieving treatment targets in bDMARD-naive patients with RA. DISCLOSURES: This study was sponsored by Amgen. Tkacz, Henderson DeYoung, and Wilson are employees of IBM Watson Health, which received funding from Amgen for this study. Collier and Oko-osi are employees and shareholders of Amgen. Gharaibeh was an employee of Amgen at the time of study execution and manuscript drafting. Data pertaining to this study were presented in a poster at AMCP Nexus 2018; October 25-28, 2018; Orlando, FL.

Assessing the Association of Formulary Copayment Changes with Real-World Treatment Patterns in Patients with Rheumatoid Arthritis on Etanercept.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic disease that requires long-term treatment to improve or maintain stable disease activity. Tumor necrosis factor inhibitors (TNFi), a class of biologic disease-modifying antirheumatic drugs (bDMARD), are effective at treating symptoms and inhibiting joint progression. Although treatment changes are not recommended in patients with stable disease, health plans have recently enacted formulary changes with higher copayments that could disrupt patient access to TNFis. OBJECTIVE: To assess the association of formulary copayment changes with real-world treatment patterns, treatment effectiveness, and health care costs among bDMARD-naive patients with RA receiving the TNFi etanercept. METHODS: This retrospective observational cohort analysis used the IBM Watson Health MarketScan Commercial Claims and Encounters Database. Adult patients with RA with 6 months of stable etanercept use (no refill gap ≥ 45 days) from January 1, 2013, through December 31, 2015, were selected and the index date was set to the first fill date after the stable-use period. Average etanercept copayment was calculated at the drug-plan level. Copayment change was defined as a monthly increase of at least $40 to account for copayment changes attributable to etanercept wholesale acquisition costs between 2014 and 2015. This amount also corresponded to the 90th percentile of average plan-level changes in etanercept copayments in the database, representing an average change in copayment by a payer. Patients were followed ≥ 12 months before and after the index date to track etanercept treatment changes and ≥ 12 months after a treatment change to track costs after etanercept copayment changes. Etanercept persistence, bDMARD switching, refill gaps, and treatment effectiveness (using a validated effectiveness algorithm) were described for patients with or without copayment change during the 12 months post-index or postchange. We also assessed the mean total of all-cause and RA-related expenditure during the 12-month post-index (or postchange) period. RESULTS: 1,970 stable patients met study inclusion criteria (mean [standard deviation] age: 50.3 [9.5] years; 77.8% female) and were evaluated. Of these, 133 (6.8%) patients had a copayment change ≥$40 during follow-up. Overall, most patients (60.3%) persisted on etanercept for the 12-month follow-up period, while 13.0% switched from etanercept, and 8.1% discontinued (refill gap of ≥ 45 days). Nearly half (48.0%) of all patients were considered effectively treated according to a validated algorithm. Compared with patients without a copayment change, those with a copayment change were more likely to switch biologics (19.5% vs. 12.6%; P = 0.021). Although statistical significance was not reached, patients with a copayment change were less likely to be persistent (54.1% vs. 60.7%; P = 0.135), and less likely to be effectively treated (42.1% vs. 48.4%; P = 0.161) than patients without a copayment change. All-cause and RA-related expenditures at baseline and post-copayment change were similar between patients with and without a copayment change. CONCLUSIONS: Changing formulary copayment of etanercept was associated with higher switching without difference in costs or health care utilization between copayment and no copayment change groups. DISCLOSURES: This study was sponsored by Amgen. Bonafede, Manjelievskaia, and Lopez-Gonzalez are employees of IBM Watson Health, which received funding from Amgen to conduct this study. Oko-osi, Collier, and Stolshek are employees and shareholders of Amgen. Gharaibeh was an employee of Amgen at the time of study execution and manuscript drafting. The authors have no other relationships that present a potential conflict of interest. Data pertaining to this study were presented in a poster at the 2018 ACR/ARHP Annual Meeting; October 19-24, 2018; Chicago, IL.

Incorporating adjustments for variability in control group response rates in network meta-analysis: a case study of biologics for rheumatoid arthritis.

BACKGROUND: The importance of adjusting for cross-study heterogeneity in control group response rates when conducting network meta-analyses (NMA) was demonstrated using a case study involving a comparison of biologics for the treatment of moderate-to-severe rheumatoid arthritis. METHODS: Bayesian NMAs were conducted for American College of Rheumatology (ACR) 50 treatment response based upon a set of randomized controlled trials (RCTs) identified by a recently completed systematic review of the literature. In addition to the performance of an unadjusted NMA, a model adjusting for cross-study heterogeneity of control group response rates using meta-regression was fit to the data. Model fit was evaluated, and findings from both analyses were compared with regard to clinical interpretations. RESULTS: ACR 50 response data from a total of 51 RCTs and 16,223 patients were analyzed. Inspection of cross-study variability in control group response rates identified considerable differences between studies. NMA incorporating adjustment for this variability was associated with an average change of 38.1% in the magnitude of the ORs between treatment comparisons, and over 64% of the odds ratio changed by 15% or more. Important changes in the clinical interpretations drawn from treatment comparisons were identified with this improved modeling approach. CONCLUSIONS: In comparing biologics for moderate to severe rheumatoid arthritis, failure to adjust for cross-trial differences in the control arm response rates in NMA can lead to biased estimates of comparative efficacy between treatments.

Persistence of tumor necrosis factor inhibitor or conventional synthetic disease-modifying antirheumatic drug monotherapy or combination therapy in psoriatic arthritis in a real-world setting.

This study described treatment patterns in a psoriatic arthritis (PsA) patient registry for new or ongoing tumor necrosis factor inhibitor (TNFi) monotherapy, conventional synthetic disease-modifying antirheumatic drug (csDMARD) monotherapy, or TNFi/csDMARD combination therapy. This retrospective analysis included adults with PsA who enrolled in the Corrona PsA/spondyloarthritis registry between March 21, 2013 (registry initiation), and January 31, 2017, and received an approved TNFi and/or csDMARD as "existing use" starting before registry entry or "initiated use" starting on/after registry entry. Therapy persistence was defined as index therapy use for ≥ 12 months without a treatment gap of ≥ 30 days. Among the evaluable patients with existing TNFi monotherapy (n = 251), csDMARD monotherapy (n = 225), and combination therapy (n = 214), 93, 87, and 87% were persistent for ≥ 12 months, and another 6, 5, and 5%, respectively, had no change with < 12 months of follow-up after first use. Among evaluable patients who initiated use of TNFi monotherapy (n = 26), csDMARD monotherapy (n = 35), and combination therapy (n = 15), 50, 43, and 53% were persistent for ≥ 12 months, and another 27, 20, and 20%, respectively, had no change with < 12 months of follow-up after first use. After initiation of index therapy, most changes (19-27% of patients) were discontinuation; 4-13% switched biologic therapy during follow-up. The results of this analysis of real-world treatment patterns in a PsA patient registry suggest that nonpersistence for TNFi monotherapy, csDMARD monotherapy, or TNFi/csDMARD combination therapy occurs more commonly after initiation of therapy than in patients with existing therapy. Trial registration: NCT02530268.

Economic Evaluation for the UK of Systemic Chemotherapies as First-Line Treatment of Metastatic Pancreatic Cancer.

BACKGROUND: Gemcitabine (GEM), oxaliplatin plus GEM (OX + GEM), cisplatin plus GEM (CIS + GEM), capecitabine plus GEM (CAP + GEM), FOLFIRINOX (FFX), and nab-paclitaxel plus GEM (NAB-P + GEM) are the most commonly used regimens as first-line treatment of metastatic pancreatic cancer (MPC) in the UK. Independent economic evaluation of these regimens simultaneously has not been conducted for the UK. OBJECTIVE: Using data from a network meta-analysis as efficacy measures, we estimated the cost effectiveness and cost utility of these regimens for the UK. METHODS: A three-state Markov model (progression-free, progressed-disease, and death) simulating the total costs and health outcomes (quality-adjusted life-years [QALYs] gained and life-years [LYs]) was developed to estimate the incremental cost-utility (ICUR) and incremental cost-effectiveness ratios (ICER) for patients with MPC, from the payer perspective. The model was specified to calculate total costs in 2017 British pounds (GBP, £). All values were discounted at 3.5% per year over a full lifetime horizon. One-way sensitivity and probabilistic sensitivity analyses were conducted to assess the impact of parameter uncertainty on the results. RESULTS: FFX was the most effective regimen, NAB-P + GEM was the most costly regimen, and GEM was the least costly and least effective regimen. OX + GEM, CIS + GEM, and NAB-P + GEM were dominated by CAP + GEM and FFX. Compared with GEM, the ICUR for CAP + GEM and FFX was £28,066 and £33,020/QALY gained, respectively; compared with GEM, the ICER for CAP + GEM and FFX was £17,437 and £22,291/LY gained, respectively; and compared with CAP + GEM, the ICUR and ICER for FFX were £34,947/QALY gained and 24,414/LY gained, respectively. CONCLUSIONS: At a threshold value of £30,000/QALY, CAP + GEM was found to be the only cost-effective regimen in the management of MPC in the UK.

Economic Evaluation for USA of Systemic Chemotherapies as First-Line Treatment of Metastatic Pancreatic Cancer.

BACKGROUND: Treatments for metastatic pancreatic cancer include monotherapy with gemcitabine (GEM); combinations of GEM with oxaliplatin (OX + GEM), cisplatin (CIS + GEM), capecitabine (CAP + GEM), or nab-paclitaxel (NAB-P + GEM); and the non-GEM combination FOLFIRINOX. Combination therapies have yielded better survival outcomes than GEM alone. A sponsor-independent economic evaluation of these regimens has not been conducted for USA. OBJECTIVE: The objective of this study was to estimate the cost utility and cost effectiveness of these regimens from the payer perspective for USA. METHODS: A three-state Markov model (progression-free, progressed disease, death) simulating the total costs and health outcomes (quality-adjusted life-years; life-years) was developed to estimate the incremental cost-utility and cost-effectiveness ratios. FOLFIRINOX clinical data were obtained from trial and indirect estimates were obtained from network meta-analyses. Lifetime horizon and 3%/year discount rates were used. RESULTS: FOLFIRINOX was the most expensive regimen and GEM the least costly regimen. Compared to GEM, all but one (CIS + GEM) regimen were found to be more effective in quality-adjusted life-years and life-years. Compared to GEM, the incremental cost-utility ratios for CAP + GEM, OX-GEM, NAB-P + GEM, and FOLFIRINOX, were US$180,503, US$197,993, US$204,833, and US$265,718 per additional quality-adjusted life-year, respectively; and the incremental cost-effectiveness ratios were US$88,181, US$87,620, US$135,683, and US$167,040 per additional life-year, respectively. A probabilistic sensitivity analysis confirmed the base-case analysis. CONCLUSIONS: This sponsor-independent economic evaluation for USA found that OX + GEM, CAP + GEM, FOLFIRINOX, and NAB-P + GEM, but not CIS + GEM, were more expensive but also more effective than GEM alone in terms of quality-adjusted life-years and life-years gained. The NAB-P + GEM regimen appears to be the most cost effective in USA at a willingness-to-pay threshold of US$200,000/quality-adjusted life-year.

Hierarchical Modeling of Patient and Physician Determinants of Blood Pressure Outcomes in Hypertensive Patients with and without Diabetes: Pooled Analysis of Six Observational Valsartan Studies with 15,282 Evaluable Patients.

We pooled data from 6 valsartan-related studies including 3,658 diabetic and 11,624 nondiabetic patients to evaluate blood pressure (BP) outcomes after approximately 90 days of second- or later-line valsartan treatment. Hierarchical linear and logistic regressions were applied to identify determinants of BP outcomes. Similar reductions in BP values and similar BP control rates were achieved in both groups after approximately 90 days of therapy. The modeling analyses identified several common and different patient- and physician-related determinants of BP outcomes for both groups, many of which are modifiable or clinically manageable. Through varying in terms of association and influence between the diabetic and nondiabetic groups, patient-related determinants included age, BP at diagnosis of hypertension, risk factors, valsartan regimen, concomitant antihypertensive treatment, and adherence; and physician-related determinants included gender, years in practice, and hypertension management. In summary, in both diabetic and nondiabetic patients, the use of valsartan-centric treatment regimens in second- or later-line antihypertensive treatment is associated with significant reductions in BP level and improvement in BP control. The determinants identified in modeling provide guidance to clinicians in the common and differential management of hypertension in diabetic and nondiabetic patients.

Cost-effectiveness of sequenced treatment of rheumatoid arthritis with targeted immune modulators.

AIMS: To determine the cost-effectiveness of treatment sequences of biologic disease-modifying anti-rheumatic drugs or Janus kinase/STAT pathway inhibitors (collectively referred to as bDMARDs) vs conventional DMARDs (cDMARDs) from the US societal perspective for treatment of patients with moderately to severely active rheumatoid arthritis (RA) with inadequate responses to cDMARDs. MATERIALS AND METHODS: An individual patient simulation model was developed that assesses the impact of treatments on disease based on clinical trial data and real-world evidence. Treatment strategies included sequences starting with etanercept, adalimumab, certolizumab, or abatacept. Each of these treatment strategies was compared with cDMARDs. Incremental cost, incremental quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for each treatment sequence relative to cDMARDs. The cost-effectiveness of each strategy was determined using a US willingness-to-pay (WTP) threshold of $150,000/QALY. RESULTS: For the base-case scenario, bDMARD treatment sequences were associated with greater treatment benefit (i.e. more QALYs), lower lost productivity costs, and greater treatment-related costs than cDMARDs. The expected ICERs for bDMARD sequences ranged from ∼$126,000 to $140,000 per QALY gained, which is below the US-specific WTP. Alternative scenarios examining the effects of homogeneous patients, dose increases, increased costs of hospitalization for severely physically impaired patients, and a lower baseline Health Assessment Questionnaire (HAQ) Disability Index score resulted in similar ICERs. CONCLUSIONS: bDMARD treatment sequences are cost-effective from a US societal perspective.

Influence of Health and Functional Status and Co-occurring Chronic Conditions on Healthcare Expenditures Among Community-dwelling Adults With Kidney Cancer in the United States: A Propensity-score-matched Analysis.

BACKGROUND: Health and functional status, as well as co-occurring chronic conditions, have a profound influence on healthcare expenditures. However, no study to date has assessed their influence among community-dwelling adults with kidney cancer (KC) in the United States (US). This study assessed the impact of health and functional status, along with co-occurring chronic conditions, on KC healthcare expenditures. METHODS: This study used a retrospective, cross-sectional, propensity-score-matched, case-control study design using 2002 to 2011 Medical Expenditure Panel Survey data. The case group was comprised of adults with KC, whereas the control group consisted of propensity-score matched adults with other forms of cancer. To examine the impact of health and functional status and co-occurring chronic conditions, ordinary least square regressions on log-transformed expenditures were conducted on total and subtypes of healthcare expenditures. The percentage change in expenditure was calculated using the formula (expß - 1). RESULTS: Findings from this study indicate that the annual average total healthcare expenditures ($15,078 vs. $8182; P < .001) for adults with KC were significantly higher compared with propensity-score-matched adults with other forms of cancer. Total healthcare expenditures for adults with KC were 80% (ß = 0.588; P < .001) higher compared with propensity-score-matched controls when only demographic characteristics were adjusted. After adjusting for health and functional status and co-occurring chronic conditions, the percentage decreased from 80% to 43% (ß = 0.359; P < .01). CONCLUSIONS: Findings from this nationally representative sample suggest that health and functional status and co-occurring chronic conditions have a significant impact on healthcare expenditures among community-dwelling adults with KC in the US.

Economic evaluation for the US of nab-paclitaxel plus gemcitabine versus FOLFIRINOX versus gemcitabine in the treatment of metastatic pancreas cancer.

BACKGROUND: Nab-paclitaxel plus gemcitabine (NAB-P + GEM) and FOLFIRINOX have shown superior efficacy over gemcitabine (GEM) in the treatment of metastatic pancreatic ductal adenocarcinoma (mPDA). Although the incremental clinical benefits are modest, both treatments represent significant advances in the treatment of a high-mortality cancer. In this independent economic evaluation for the US, the aim was to estimate the comparative cost-utility and cost-effectiveness of these three regimens from the payer perspective. METHODS: In the absence of a direct treatment comparison in a single clinical trial, the Bucher indirect comparison method was used to estimate the comparative efficacy of each regimen. A Markov model evaluated life years (LY) and quality-adjusted life years (QALY) gained with NAB-P + GEM and FOLFIRINOX over GEM, expressed as incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR). All costs and outcomes were discounted at 3%/year. The impact of parameter uncertainty on the model was assessed by probabilistic sensitivity analyses. RESULTS: NAB-P + GEM was associated with differentials of +0.180 LY and +0.127 QALY gained over GEM at an incremental total cost of $25,965; yielding an ICER of $144,096/LY and ICUR of $204,369/QALY gained. FOLFIRINOX was associated with differentials of +0.368 LY and +0.249 QALY gained over GEM at an incremental total cost of $93,045; yielding an ICER of $253,162/LY and ICUR of $372,813/QALY gained. In indirect comparison, the overall survival hazard ratio (OS HR) for NAB-P + GEM vs FOLFIRINOX was 0.79 (95%CI = 0.59-1.05), indicating no superiority in OS of either regimen. FOLFIRINOX had an ICER of $358,067/LY and an ICUR of $547,480/QALY gained over NAB-P + GEM. Tornado diagrams identified variation in the OS HR, but no other parameters, to impact the NAB-P + GEM and FOLFIRINOX ICURs. CONCLUSIONS: In the absence of a statistically significant difference in OS between NAB-P + GEM and FOLFIRINOX, this US analysis indicates that the greater economic benefit in terms of cost-savings and incremental cost-effectiveness and cost-utility ratios favors NAB-P + GEM over FOLFIRINOX.

Economic Evaluations of First-Line Chemotherapy Regimens for Pancreatic Cancer: A Critical Review.

Effect sizes of efficacy of first-line treatments for (metastatic) pancreas cancer are constrained, underscoring the need for evaluations of the efficacy-to-cost relationship. We critically review economic evaluations of first-line chemotherapy regimens for pancreatic cancer since the 1997 introduction of gemcitabine. We searched PubMed/MEDLINE and EMBASE (1997-2015), and the websites of health technology assessment agencies. Two authors independently reviewed economic studies for eligibility in this review; evaluated peer-reviewed, journal-published studies in terms of the Drummond Checklist; and critiqued the technical and scientific merit of all studies. Sixteen pharmacoeconomic evaluations were included: ten published in nine peer-reviewed journals and six on three websites. Six were on single-agent therapies and ten on combination therapies. Analyses conducted included cost-effectiveness (three studies), cost-utility (one study), or combined cost-effectiveness and cost-utility (12 studies). Studies diverged in results, mainly because of different assumptions, methods, inputs, and country-specific guidelines. The two most recent regimens, nanoparticle albumin-bound paclitaxel plus gemcitabine (NAB-P + GEM) and the combination of fluorouracil, oxaliplatin, leucovorin, and irinotecan (FOLFIRINOX), were evaluated in an indirect comparison, yielding a statistically similar benefit in overall survival but superior progression-free survival for FOLFIRINOX. NAB-P + GEM showed greater economic benefit over FOLFIRINOX. In conclusion, the divergence in results observed across studies is attributable to economic drivers that are specific to countries and their healthcare (financing) systems. No recommendations regarding the relative economic benefit of treatment regimens, general or country-specific, are made as the purpose of pharmacoeconomic analysis is to inform policy decision-making and clinical practice, not set policy or define clinical practice.

Cost-effectiveness of anticoagulants for suspected heparin-induced thrombocytopenia in the United States.

Despite the availability of multiple nonheparin anticoagulants for the treatment of heparin-induced thrombocytopenia (HIT), few data are available comparing the cost-effectiveness of these agents. This analysis is particularly important when considering differences in the risk of adverse effects, routes of administration, requirements for phlebotomy and laboratory monitoring, and overall drug costs. We conducted a cost-effectiveness analysis of argatroban, bivalirudin, and fondaparinux for the treatment of suspected HIT from the institutional perspective. A 3-arm decision-tree model was developed that employs standard practices for anticoagulation monitoring. We incorporated published data on drug efficacy and probability of HIT-related thromboembolism and major bleeding. We considered both institutional costs and average wholesale price (AWP) and performed probabilistic sensitivity analyses (PSA) to address any uncertainty in model parameters. Using institutional costs, fondaparinux prevailed over both argatroban and bivalirudin in terms of cost ($151 vs $1250 and $1466, respectively) and adverse events averted (0.9989 vs 0.9957 and 0.9947, respectively). Results were consistent when AWP was used, with fondaparinux being less expensive ($555 vs $3081 and $2187, respectively) and more effective in terms of adverse events averted (0.9989 vs 0.9957 and 0.9947, respectively). The PSA confirmed our findings using both institutional costs and AWP. In conclusion, fondaparinux subcutaneous injection afforded significant advantages in terms of cost savings and adverse events averted compared with IV argatroban or bivalirudin infusions. Our data strongly suggest potential cost savings with fondaparinux and underscore the critical need for larger clinical studies of fondaparinux in the treatment of suspected HIT.