Financial Implications of Avapritinib for Treatment of Unresectable Gastrointestinal Stromal Tumors in Patients With a PDGFRA Exon 18 Variant or After 3 Previous Therapies in a Hypothetical US Health Plan.

Importance: With the approval of avapritinib for adults with unresectable or metastatic gastrointestinal stromal tumors (GISTs) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 variant, including PDGFRA D842V variants, and National Comprehensive Cancer Network guideline recommendations as an option for patients with GIST after third-line treatment, it is important to estimate the potential financial implications of avapritinib on a payer's budget. Objective: To estimate the budget impact associated with the introduction of avapritinib to a formulary for metastatic or unresectable GISTs in patients with a PDGFRA exon 18 variant or after 3 or more previous treatments from the perspective of a US health plan. Design, Setting, and Participants: For this economic evaluation, a 3-year budget impact model was developed in March 2020, incorporating costs for drug acquisition, testing, monitoring, adverse events, and postprogression treatment. The model assumed that avapritinib introduction would be associated with increased PDGFRA testing rates from the current 49% to 69%. The health plan population was assumed to be mixed 69% commercial, 22% Medicare, and 9% Medicaid. Base case assumptions included a GIST incidence rate of 9.6 diagnoses per million people, a metastatic PDGFRA exon 18 mutation rate of 1.9%, and progression rate from first-line to fourth-line treatment of 17%. Exposures: The model compared scenarios with and without avapritinib in a formulary. Main Outcomes and Measures: Annual, total, and per member per month (PMPM) budget impact. Results: In a hypothetical 1-million member plan, fewer than 0.1 new patients with a PDGFRA exon 18 variant per year and 1.2 patients receiving fourth-line therapy per year were eligible for treatment. With avapritinib available, the total increase in costs in year 3 for all eligible adult patients with a PDGFRA exon 18 variant was $46 875, or $0.004 PMPM. For patients undergoing fourth-line treatment, the total increase in costs in year 3 was $69 182, or $0.006 PMPM. The combined total budget impact in year 3 was $115 604, or $0.010 PMPM, including an offset of $3607 in postprogression costs avoided or delayed. The higher rates of molecular testing resulted in a minimal incremental testing cost of $453 in year 3. Conclusions and Relevance: These results suggest that adoption of avapritinib as a treatment option would have a minimal budget impact to a hypothetical US health plan. This would be primarily attributable to the small eligible patient population and cost offsets from reduced or delayed postprogression costs.

Cost-utility analysis of a 'vonoprazan-first' strategy versus 'esomeprazole- or rabeprazole-first' strategy in GERD.

BACKGROUND: Gastroesophageal reflux disease (GERD) can be treated using a vonoprazan-first strategy (first-line treatment with vonoprazan), or esomeprazole-first/rabeprazole-first strategies (first-line treatment with proton-pump inhibitors [PPIs], esomeprazole/rabeprazole, followed by a switch to vonoprazan). This cost-utility analysis used long-term simulation modeling to evaluate the cost-effectiveness of a vonoprazan-first strategy compared with the esomeprazole-first and rabeprazole-first strategies. METHODS: A Markov simulation model was developed to evaluate the cost-effectiveness of vonoprazan-first, esomeprazole-first, and rabeprazole-first strategies, comprising healing and maintenance therapies, over 5 years (4-week cycles). Healing therapy began with the administration of a normal dose of drug per real-world practice. If patients were not healed endoscopically, either a longer duration of healing therapy was provided (vonoprazan), the dose was increased (rabeprazole), or patients were switched to vonoprazan (immediately for esomeprazole, and after dose-escalation for rabeprazole, respectively). Healed patients received maintenance (lower/same dose as healing therapy). Recurrence resulted in re-challenge with healing therapy. Transition probabilities were derived from the results of indirect comparisons (network meta-analysis) and costs calculated from the Japanese payer perspective. Outcomes were defined as quality-adjusted life years (QALYs), with utilities based on published values. RESULTS: Expected costs of the vonoprazan-, esomeprazole-, and rabeprazole-first strategies were ¥36,194, ¥76,719, and ¥41,105, respectively, over 5 years. QALY gains for vonoprazan-first strategy versus the esomeprazole- and rabeprazole-first strategies were 0.014 and 0.003, respectively. Both estimated incremental cost-effectiveness ratios were dominant and robust to two sensitivity analyses. CONCLUSIONS: Vonoprazan-first strategy increased QALYs and appeared to be cost-effective for GERD patients compared with the esomeprazole- or rabeprazole-first strategies.

Budget impact of introducing tofacitinib to the public hospital formulary in Hong Kong, 2017-2021.

INTRODUCTION: As the first approved oral kinase inhibitor, tofacitinib is effective and well-tolerated, but more expensive than conventional treatments for uncontrolled rheumatoid arthritis. Public formulary listing typically exerts a positive impact on the uptake of new drugs. We aimed to assess the budgetary impact of introducing tofacitinib into the Hospital Authority Drug Formulary as a fully subsidised drug in Hong Kong. METHODS: We applied a population-based budget impact model to trace the number of eligible patients receiving biologics or tofacitinib treatment, then estimated the 5-year healthcare expenditure on rheumatoid arthritis treatments, with or without tofacitinib (2017-2021). We used linear regression to estimate the number of target patients and compound annual growth rate to estimate market share. Competing treatments included abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, and tofacitinib. Retail price was used for drug costs, valued in Hong Kong dollars (HK$) in 2017 and discounted at 4% per year. RESULTS: The annual treatment cost of tofacitinib was HK$74 214 per patient, and the costs of biologics ranged from HK$64 350 to HK$115 700. Without tofacitinib, the annual government health expenditures for rheumatoid arthritis treatment were estimated to increase from HK$147.9 million (2017) to HK$190.6 million (2021). The introduction of tofacitinib to the formulary would reduce healthcare expenditures by 17.3% to 20.3% per year, with cumulative savings of HK$192.8 million; this change was estimated to provide consistent savings (HK$66.4 million to HK$196.8 million) in all tested scenarios. CONCLUSION: Introduction of tofacitinib to the formulary will provide 5-year savings, given the current drug price and patient volume.

Vonoprazan versus Lansoprazole for the Initial Treatment of Reflux Esophagitis: A Cost-effectiveness Analysis in Japan.

Objective Gastroesophageal reflux disease (GERD) is a highly prevalent disorder that negatively affects patients' quality of life and reduces their work productivity. The medical expenses associated with the treatment of GERD are the highest among all digestive diseases. Current guidelines recommend the administration of a standard dose of proton pump inhibitor (PPI) for eight weeks as an initial GERD treatment. However, there is growing concern regarding the safety of PPI treatment. Recently, a novel potassium-competitive acid blocker (P-CAB), vonoprazan (VPZ), was approved for the treatment of reflux esophagitis in Japan and may provide clinical benefits in GERD treatment. This study was conducted to evaluate the cost-effectiveness of a P-CAB, VPZ vs. a PPI, lansoprazole (LPZ), for the acute medical treatment of reflux esophagitis. Methods A clinical decision analysis was performed using a Markov chain approach to compare VPZ to LPZ in the acute treatment of reflux esophagitis in Japan. Results The P-CAB strategy was superior to the PPI strategy in terms of cost-effectiveness (direct cost per patient to achieve clinical success) and the number of days for which medication was required. Sensitivity analyses revealed that this superiority was robust within the plausible range of probabilities. This remained true even when the healing rates in cases of mild esophagitis were applied. Conclusion The P-CAB strategy was consistently superior to the conventional PPI strategy using the original LPZ in terms of cost-effectiveness and the number of days for which medication was required. Thus, VPZ appears to be the drug of choice for the acute medical treatment of reflux esophagitis.

Tofacitinib in the treatment of moderate-to-severe rheumatoid arthritis: a cost-effectiveness analysis compared with adalimumab in Taiwan.

Aims: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This analysis investigated the cost-effectiveness of the second-line treatment with tofacitinib, compared with adalimumab, both plus methotrexate (MTX), in patients with moderate-to-severe RA and an inadequate response to the first-line MTX, from a Taiwan National Health Insurance Administration perspective. Materials and methods: A patient-level simulation model was used to project lifetime costs and quality-adjusted life-years (QALYs). Base-case analysis compared second-line treatment with tofacitinib 5 mg twice daily plus MTX vs adalimumab 40 mg every 2 weeks plus MTX. Patients switched or discontinued treatment due to a lack or loss of effectiveness or a serious adverse event. Efficacy was measured by change in Health Assessment Questionnaire-Disability Index (HAQ-DI) score. HAQ-DI scores were used to predict mortality and resource utilization, and were mapped onto utility values to estimate QALYs. Efficacy and safety data were derived from clinical trials and other secondary sources. Uncertainty in model parameters was explored using one-way deterministic and probabilistic sensitivity analyses. Results: Patients gained 0.09 more QALYs with second-line tofacitinib plus MTX compared with adalimumab plus MTX (5.13 vs 5.04, respectively) at an additional cost of New Taiwan Dollars (NT$) 12,881. The incremental cost-effectiveness ratio was NT$143,122/QALY. One-way sensitivity analysis confirmed the base-case result was robust. Limitations: The lack of available clinical data, particularly for HAQ-DI scores, may introduce some bias in the analysis. No patients were in an early stage of RA, which may limit the generalizability of these results. Base-case results from our study are not necessarily generalizable to countries with healthcare systems that differ considerably from Taiwan. Conclusions: From a payer perspective, second-line treatment with tofacitinib plus MTX is a cost-effective treatment strategy, compared with adalimumab plus MTX, in patients with moderate-to-severe RA in Taiwan.

An economic evaluation of tofacitinib for the treatment of moderately-to-severely active ulcerative colitis: modeling the cost of treatment strategies in the United States.

Aims: To evaluate the cost differences between a treatment strategy including tofacitinib (TOFA) vs treatment strategies including adalimumab (ADA), golimumab (GOL), infliximab (IFX), and vedolizumab (VEDO) among all patients with moderate-to-severe ulcerative colitis (UC) (further stratified by patients naïve/exposed to tumor necrosis factor inhibitors [TNFis]). Materials and methods: An Excel-based decision-analytic model was developed to evaluate costs from the perspective of a third-party US payer over 2 years. Efficacy and safety parameters were taken from prescribing information and published trials. All patients started induction therapy on the first treatment in the strategy and continued if efficacy criteria were met and no major adverse event occurred (in which cases they proceeded to the next treatment in the strategy). Results: The cost per member per month (PMPM) of the TOFA->IFX->VEDO->GOL strategy ($1.11) was lower than that of the ADA->IFX->VEDO->GOL strategy ($1.34; Δ = $-0.23) among the TNFi-naïve population (n = 204 patients out of a plan of one million members). Similarly, the use of TOFA before ADA (i.e. TOFA->ADA->IFX-> VEDO) was also associated with lower PMPM costs than the use of ADA before TOFA (i.e. ADA->TOFA->IFX->VEDO): $1.15 vs $1.25 (Δ = $-0.10). Similar, and often larger, differences were observed in both the overall moderate-to-severe population and the TNFi-exposed population. Sensitivity analyses resulted in the same conclusions. Limitations: Our model relied on efficacy data from prescribing information and published trials, which were not head-to-head and slightly differed with respect to methods. Additionally, our model used representative minor and major ADRs (and the associated costs) to represent toxicity management, which was a simplifying assumption. Conclusions: This analysis, the first of its kind to evaluate TOFA vis-à-vis other advanced therapies in the US, suggests the early use of TOFA among both TNFi-naïve and TNFi-failure patients results in lower PMPM costs compared with other treatment alternatives.

Cost-effectiveness analysis and effectiveness of pharmacist-managed outpatient clinics in Helicobacter pylori eradication therapy.

BACKGROUND: Helicobacter pylori is involved in many upper gastrointestinal diseases such as peptic ulcers and gastric cancers. In this study, we compared the cost-effectiveness of lansoprazole and vonoprazan in H. pylori eradication therapy and examined the effectiveness of pharmacist-managed outpatient clinics. METHODS: We investigated the efficacy and cost-effectiveness of pharmacist-managed outpatient clinics in H. pylori eradication therapy at our hospital from January 2015 to December 2017. The subjects were classified into three groups: lansoprazole group; vonoprazan group; and the medication instruction group, which received instructions at the pharmacist-managed outpatient clinics (intervention group). We examined the eradication rate and cost-effectiveness ratio of each group. RESULTS: The eradication rate of primary eradication therapy was 75.2% in the lansoprazole group, 87.8% in the vonoprazan group and 91.4% in the intervention group. When mental component summary was used as quality of life score, cost-effectiveness ratio was 224.7 yen in lansoprazole group, 223.9 yen in vonoprazan group and 222.2 yen in intervention group. Setting up pharmacist-managed outpatient clinics increases the pharmacist labour cost necessary for eradication therapy. However, if the medication instructions provided by the pharmacist can lead to improved disinfection efficiency, improvement in cost efficiency can be expected. CONCLUSION: Although medication instructions provided at the pharmacist-managed outpatient clinics incur additional labour costs, they improve patient quality of life as well as disinfection rate in H. pylori eradication therapy. Therefore, pharmacist-managed outpatient clinics are useful from the viewpoint of pharmacoeconomics.

[A Cost-effectiveness Analysis of Sunitinib vs. Interferon-alpha in Patient with Advanced Renal Cell Carcinoma in Japan].

Sunitinib has been shown to offer clinical benefits during the treatment of advanced renal cell carcinoma. However, molecular targeting drugs are expensive and can have a significant impact on medical expenses. The purpose of this study was to assess the cost-effectiveness of sunitinib as a first-line therapy compared with interferon-alpha (IFN-α) in metastatic renal cell carcinoma patients. A Markov model was used to show the clinical courses of patients with metastatic renal cell carcinoma who received sunitinib or IFN-α. The transition probabilities and utilities employed in this Markov model were derived from two sources. This study focused on the perspective of public healthcare payer, as only direct medical costs were estimated from the treatment schedule for metastatic renal cell cancer. In the cost-effectiveness analysis, outcomes were valued in terms of life years (LYs) and quality-adjusted life years (QALYs). We calculated the incremental cost-effectiveness ratio (ICER) during the cost-effectiveness analysis. The results were tested using Monte Carlo simulations. Sunitinib and IFN-α treatment resulted in LYs of 2.40 years and 2.03 years, QALYs of 1.58 and 1.25, and expected costs of 13,572,629 yen and 6,083,002 yen, respectively. As a result, the ICER associated with replacing IFN-α with sunitinib was 22,695,839 yen/QALYs. Our results suggest that compared with IFN-α, sunitinib prolongs LYs and QALYs, but the increases in quality achieved by sunitinib are more expensive than those produced by IFN-α.

Modelling the cost-effectiveness of tofacitinib for the treatment of rheumatoid arthritis in the United States.

BACKGROUND AND OBJECTIVES: Rheumatoid arthritis (RA) is a chronic, debilitating disease affecting an estimated 1.5 million patients in the US. The condition is associated with a substantial health and economic burden. An economic model was developed to evaluate the cost-effectiveness of tofacitinib (a novel oral Janus kinase inhibitor) versus biologic therapies commonly prescribed in the US for the treatment of RA. METHODS: A cost-utility model was developed whereby sequences of treatments were evaluated. Response to treatment was modeled by HAQ change, and informed by a network meta-analysis. Mortality, resource use and quality of life were captured in the model using published regression analyses based on HAQ score. Treatment discontinuation was linked to response to treatment and to adverse events. Patients were modeled as having had an inadequate response to methotrexate (MTX-IR), or to a first biologic therapy (TNFi-IR). RESULTS: The tofacitinib strategy was associated with cost savings compared with alternative treatment sequences across all modeled scenarios (i.e. in both the MTX-IR and TNFi-IR scenarios), with lifetime cost savings per patient ranging from $65,205 to $93,959 (2015 costs). Cost savings arose due to improved functioning and the resulting savings in healthcare expenditure, and lower drug and administration costs. The tofacitinib strategies all resulted in an increase in quality-adjusted life years (QALYs), with additional QALYs per patient ranging from 0.01 to 0.22. CONCLUSIONS: Tofacitinib as a second-line therapy following methotrexate failure and as a third-line therapy following a biologic failure produces lower costs and improved quality of life compared with the current pathway of care.

An Economic Evaluation of Tofacitinib Treatment in Rheumatoid Arthritis After Methotrexate or After 1 or 2 TNF Inhibitors from a U.S. Payer Perspective.

BACKGROUND: Treatment cycling with biologic disease-modifying anti-rheumatic drugs, such as tumor necrosis factor inhibitors (TNFi), is common among patients with rheumatoid arthritis (RA) and can result in reduced clinical efficacy and increased economic burden. Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. OBJECTIVE: To evaluate and compare the economic effect of tofacitinib 5 mg twice daily (BID) treatment directly after methotrexate (MTX) in the MTX-inadequate responder population, or after MTX and 1 TNFi (adalimumab [ADA] or etanercept [ETN]) or 2 TNFi (ADA and ETN) in TNF-inadequate responder patients with RA, from a U.S. payer perspective. METHODS: A decision-tree economic model was used to evaluate costs over 2 years. Treatment response was modeled as American College of Rheumatology (ACR) 20/50/70 response. ACR response rates at 6-month intervals were derived from U.S. prescribing information for monotherapy and combination therapy. Safety event rates were sourced from a meta-analysis. It was assumed that 75% of patients switched therapy after an adverse event or lack of response. Cost inputs included drugs, monitoring and administration (including physician visits), health care utilization, and treatment for adverse events. The population comprised all organization members (i.e., RA and non-RA members); RA patients receiving TNFi were estimated using epidemiologic data. Results were based on an organization size of 1 million. Economic endpoints were total 2-year costs, costs per member per month (PMPM), and costs per ACR20/50 responder. RESULTS: 1,321 patients were included for analysis. Based on ACR20 switch criteria and either 100% or 50% monotherapy rates for all treatments, total 2-year costs and costs PMPM were lower for patients receiving tofacitinib as second-line therapy after MTX and as third-line therapy after MTX and 1 TNFi; costs were highest for patients who cycled through 2 TNFi. Similar trends were observed for switch criteria based on ACR50 response and addition of 20% rebates for ADA and ETN and 0% for tofacitinib, although differences were mitigated slightly. CONCLUSIONS: A treatment strategy with tofacitinib as either second- or third-line therapy after MTX may be a lower cost treatment option, compared with fourth-line introduction of tofacitinib after cycling through 2 TNFi following MTX. DISCLOSURES: All aspects of this study were funded by Pfizer. Claxton was an employee of York Health Economics Consortium, University of York, at the time of this study. Taylor is an employee of York Health Economics Consortium, The University of York, which received funding from Pfizer to conduct this study. Soonasra, Bourret, and Gerber are employees of Pfizer and hold stock/stock options in Pfizer. A previous iteration of the data reported in this manuscript (before adjustment for recent drug price increases) was presented at the Academy of Managed Care Pharmacy 28th Annual Meeting and Expo; April 19-22, 2016; held in San Francisco, CA.

Cost-Effectiveness of Different Strategies for the Treatment of Moderate-to-Severe Ulcerative Colitis.

Background: Knowledge regarding the economic outcomes of anti-tumour necrosis factor-α (anti-TNFα) and oral Janus kinase inhibitor (JAKi) therapies for the treatment of ulcerative colitis (UC) is limited. We conducted this analysis to assess the economic outcomes of anti-TNFα, antiadhesion molecule inhibitors (anti-AMi), and oral JAKi therapies for the treatment of UC from the perspectives of the United Kingdom (UK) and China, which are the representatives of high-income and middle-income regions, respectively. Methods: A Markov model-based economic analysis was performed by incorporating effectiveness and utility data obtained from the literature and costs based on publicly available reports. The UK and Chinese health care perspectives were adopted to evaluate different intervention treatment sequences, including 14 treatment sequences consisting of conventional therapy, tofacitinib, adalimumab, vedolizumab, golimumab, and infliximab. The participants were the patients with moderate-to-severe UC eligible for anti-TNFα, anti-Ami, and JAKi treatment. Cost, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) were reported. Results: Compared to other alternatives comprising adalimumab, golimumab, and infliximab, the use of a treatment sequence comprising tofacitinib and vedolizumab always had better health outcomes. The most cost-effective options in the UK included the sequences comprising tofacitinib and vedolizumab, and the most cost-effective treatment option in China was tofacitinib. There were uncertainties surrounding the results, the key drivers of which being the utility values, effectiveness of conventional therapy, and relative efficacy of the active treatments. Conclusions: The treatment with tofacitinib and vedolizumab for moderate-to-severe UC is likely to be the most favorable cost-effective option in the high-income UK, and tofacitinib is the most cost-effective option in the middle-income China.

Real-World Economic Outcomes During Time on Treatment Among Patients Who Initiated Sunitinib or Pazopanib as First Targeted Therapy for Advanced Renal Cell Carcinoma: A Retrospective Analysis of Medicare Claims Data.

BACKGROUND: The median age at renal cell carcinoma (RCC) diagnosis is 64 years. However, few studies have assessed the real-world time on treatment (TOT), health resource utilization (HRU), costs, or treatment compliance associated with targeted therapy use among patients in this age group with RCC. OBJECTIVE: To assess the HRU, costs, and compliance during TOT among Medicare patients aged ≥ 65 years with advanced RCC (aRCC) who initiated first targeted therapy with pazopanib or sunitinib. METHODS: Patients with aRCC were identified in the 100% Medicare + Part D databases administered by the Centers for Medicare & Medicaid Services. Eligible patients initiated first targeted therapy with sunitinib or pazopanib (index drug) on or after their first diagnosis of secondary neoplasm between October 19, 2009, and January 1, 2014, and were aged ≥ 65 years as of 1 year before first targeted therapy initiation (index date). Included patients were stratified into pazopanib and sunitinib cohorts based on first targeted therapy and matched 1:1 on baseline characteristics using propensity scores. TOT was defined as the time from the index date to treatment discontinuation (prescription gap > 90 days) or death. Compliance was defined as the ratio of drug supply days to TOT. Monthly all-cause costs and costs associated with RCC diagnosis (medical and pharmacy in 2015 U.S. dollars) and HRU (inpatient [admissions, readmissions, and days], outpatient, and emergency room visits) were assessed in the 1-year post-index period during TOT. Matched cohorts' TOT was compared using Kaplan-Meier analyses and univariable Cox models, and compliance, HRU, and costs were compared using Wilcoxon signed-rank tests. RESULTS: Of 1,711 included patients, 526 initiated pazopanib and 1,185 initiated sunitinib. Before matching, more patients in the pazopanib cohort were white, diagnosed in 2010-2014 versus 2006-2009, and had lung metastases compared with the sunitinib cohort (all P < 0.05). The pazopanib cohort also had higher mean outpatient visits and costs but lower mean total all-cause pharmacy costs, than the sunitinib cohort (all P < 0.05). After matching, the pazopanib and sunitinib cohorts had similar characteristics (mean age 75 years, 58% male, and Charlson Comorbidity Index score of 9.2 in both cohorts) and median TOT (4.8 and 4.1 months, respectively). Among the 522 matched pairs, pazopanib was associated with significantly lower total all-cause health care costs ($8,527 vs. $10,924, respectively [mean difference = $2,397]); total medical costs ($3,991 vs. $5,881, respectively, [$1,890]); and inpatient costs ($2,040 vs. $3,731, respectively, [$1,692]; all P < 0.01) compared with sunitinib. Patients receiving pazopanib had significantly fewer inpatient admissions (0.179 vs. 0.289, respectively) and days (1.063 vs. 1.904, respectively; both P < 0.01) than patients receiving sunitinib. Mean treatment compliance was lower for the pazopanib versus sunitinib cohort (0.91 vs. 0.94, respectively; P < 0.01). CONCLUSIONS: In this retrospective analysis of Medicare patients with aRCC from a TOT perspective, first targeted therapy with pazopanib was associated with significantly lower all-cause health care costs and HRU, but lower compliance, compared with sunitinib. DISCLOSURES: Funding for this research was provided by Novartis Pharmaceuticals. The sponsor was involved in all stages of the study's conduct and reporting. Vogelzang has been a consultant for Novartis, Amgen, Celgene, Medivation, Eisai, Exelixis, and Roche; has spoken at Novartis, Astellas, Johnson and Johnson, Pfizer, Dendreon, Bayer/Algeta, GSK, and Veridex/Janssen; and has received research support from Novartis, Bayer, Exelixis, Progenics, Bavarian Nordic, and Viamet. Pal has been a consultant for Novartis, Pfizer, Aveo, Dendreon, and Myriad and has spoken at Novartis, Pfizer and Medivation. Agarwal has been a consultant or advisor for Novartis, Pfizer, Exelixis, Cerulean Pharma, Medivation, Eisai, and Argos Therapeutics. Swallow, Peeples, Zichlin, and Meiselbach are employees of Analysis Group, which received consultancy fees from Novartis for this project. Li was an employee of Analysis Group during the conduct of this study. Ghate is an employee of Novartis and owns stock/stock options. Perez was an employee of Novartis during the conduct of this study. A synopsis of the economic outcomes was presented at the Academy of Managed Care Pharmacy Nexus 2017 in Denver, Colorado, during March 27-30, 2017. A synopsis of the clinical outcomes was presented at the 22nd ISPOR Annual International Meeting in Boston, Massachusetts, during May 20-24, 2017.

Tofacitinib for Treating Rheumatoid Arthritis After the Failure of Disease-Modifying Anti-rheumatic Drugs: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its Single Technology Appraisal process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (Pfizer) of tofacitinib (TOF; Xeljanz®) to submit evidence of the drug's clinical and cost-effectiveness in the treatment of rheumatoid arthritis (RA) after the failure of conventional disease-modifying antirheumatic drugs (cDMARDs). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a detailed review of the evidence for the clinical and cost-effectiveness of the technology, based upon the company's submission to NICE. The clinical effectiveness evidence in the company's submission for TOF is based predominantly on four randomised controlled trials (RCTs) comparing the efficacy of TOF against placebo. Three RCTs investigated TOF in combination with methotrexate (MTX), and one RCT investigated TOF monotherapy. All four RCTs compared TOF with placebo plus cDMARDs, one RCT also included adalimumab as a comparator. The study population in the four RCTs comprised patients who were MTX inadequate responders or cDMARD inadequate responders (cDMARD-IR). The company performed network meta-analyses (NMA) to assess the relative efficacy of TOF compared with biologic DMARDs (bDMARDs) in patients who were cDMARD-IR or bDMARD-IR with moderate-to-severe RA for European League Against Rheumatism (EULAR) response and change in the Health Assessment Questionnaire Disability Index at 6 months. The company's NMA concluded that TOF had comparable efficacy to bDMARDs currently recommended by NICE. The company submitted a de novo model that assessed the cost-effectiveness of TOF versus its comparators in six different populations: (1) cDMARD-IR with severe RA; (2) cDMARD-IR with severe RA for whom MTX is contraindicated or not tolerated; (3) bDMARD-IR; (4) bDMARD-IR for whom rituximab (RTX) is contraindicated or not tolerated; (5) bDMARD-IR for whom MTX is contraindicated or not tolerated; and, (6) cDMARD-IR with moderate RA. According to the company's economic analyses, in cDMARD-IR with severe RA, TOF plus MTX dominates or extendedly dominates most comparators, whilst TOF monotherapy is slightly less effective and less expensive than its comparators, with the cost saved per quality-adjusted life year (QALY) lost always higher than £50,000. In bDMARD-IR with severe RA, RTX plus MTX dominated TOF plus MTX, but in patients for whom RTX was not an option, TOF plus MTX dominated all comparators included in the analysis (four comparators recommended by NICE were not included). In cDMARD-IR with moderate RA, the cost per QALY for TOF in combination with MTX or as monotherapy compared with a sequence of cDMARDs was estimated to be greater than £50,000/QALY. The ERG identified a number of limitations in the company's analyses, including use of a fixed-effects model in the NMA and the use of treatment sequences in the cost-effectiveness model which did not reflect NICE recommendations. These limitations were addressed partly by the company during the clarification round and partly by the ERG. The exploratory analyses undertaken by the ERG resulted in similar conclusions: (1) TOF plus MTX was dominated by RTX plus MTX; (2) TOF in combination with MTX or as monotherapy dominates or extendedly dominates some of its comparators in cDMARD-IR and bDMARD-IR with severe RA for whom RTX plus MTX was not an option; and (3) in cDMARD-IR with moderate RA, the cost per QALY of TOF in combination with MTX or as a monotherapy versus cDMARDs was in excess of £47,000. The NICE Appraisal Committee consequently recommended TOF plus MTX as an option for patients whose disease has responded inadequately to intensive therapy with a combination of cDMARDs only if (1) disease is severe [a Disease Activity Score (DAS28) of more than 5.1] and (2) the company provides TOF with the discount agreed in the Patient Access Scheme (PAS). TOF plus MTX is also recommended as an option for adults whose disease has responded inadequately to, or who cannot have, other DMARDs, including at least one bDMARD, only if (1) disease is severe, (2) they cannot have RTX, and (3) the company provides TOF with the discount agreed in the PAS. For patients who are intolerant of MTX, or where MTX is contraindicated, TOF monotherapy is recommended where TOF plus MTX would be recommended.

Treatment Persistence and Healthcare Costs Among Patients with Rheumatoid Arthritis Changing Biologics in the USA.

INTRODUCTION: After a patient with rheumatoid arthritis (RA) fails tumor necrosis factor inhibitor (TNFi) treatment, clinical guidelines support either cycling to another TNFi or switching to a different mechanism of action (MOA), but payers often require TNFi cycling before they reimburse switching MOA. This study examined treatment persistence, cost, and cost per persistent patient among MOA switchers versus TNFi cyclers. METHODS: This study of Commercial and Medicare Advantage claims data from the Optum Research Database included patients with RA and at least one claim for a TNFi (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) between January 2012 and September 2015 who changed to another TNFi or a different MOA therapy (abatacept, tocilizumab, or tofacitinib) within 1 year. The index date was the date of the change in therapy. Treatment persistence was defined as no subsequent switch or 60-day gap in therapy for 1 year post-index. RA-related costs included plan-paid and patient-paid amounts for inpatient, outpatient, and pharmacy claims. Medication costs included index and post-index costs of TNFi and different MOA therapies. RESULTS: There were 581 (38.3%) MOA switchers and 935 (61.7%) TNFi cyclers. The treatment persistence rate was significantly higher for MOA switchers versus TNFi cyclers (47.7% versus 40.2%, P = 0.004). Mean 1-year healthcare costs were significantly lower among MOA switchers versus TNFi cyclers for total RA-related costs ($37,804 versus $42,116; P < 0.001) and medication costs ($29,001 versus $34,917; P < 0.001). When costs were divided by treatment persistence, costs per persistent patient were lower among MOA switchers versus TNFi cyclers: $25,436 lower total RA-related cost and $25,999 lower medication costs. CONCLUSION: MOA switching is associated with higher treatment persistence and lower healthcare costs than TNFi cycling. Reimbursement policies that require patients to cycle TNFi before switching MOA may result in suboptimal outcomes for both patients and payers. FUNDING: Sanofi and Regeneron Pharmaceuticals.

Estimated medical expenditure and risk of job loss among rheumatoid arthritis patients undergoing tofacitinib treatment: post hoc analyses of two randomized clinical trials.

Objectives: RA causes high disability levels and reduces health-related quality of life, triggering increased costs and risk of unemployment. Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. These post hoc analyses of phase 3 data aimed to assess monthly medical expenditure (MME) and risk of job loss for tofacitinib treatment vs placebo. Methods: Data analysed were from two randomized phase 3 studies of RA patients (n = 1115) with inadequate response to MTX or TNF inhibitors (TNFi) receiving tofacitinib 5 or 10 mg twice daily, adalimumab (one study only) or placebo, in combination with MTX. Short Form 36 version 2 Health Survey physical and mental component summary scores were translated into predicted MME via an algorithm and concurrent inability to work and job loss risks at 6, 12 and 24 months, using Medical Outcomes Study data. Results: MME reduction by month 3 was $100 greater for tofacitinib- than placebo-treated TNFi inadequate responders (P < 0.001); >20 and 6% reductions from baseline, respectively. By month 3 of tofacitinib treatment, the odds of inability to work decreased ⩾16%, and risk of future job loss decreased ∼20% (P < 0.001 vs placebo). MME reduction by month 3 was $70 greater for tofacitinib- than placebo-treated MTX inadequate responders (P < 0.001); ⩾23 and 13% reductions from baseline, respectively. By month 3 of tofacitinib treatment, the odds of inability to work decreased ⩾31% and risk of future job loss decreased ⩾25% (P < 0.001 vs placebo). Conclusion: Tofacitinib treatment had a positive impact on estimated medical expenditure and risk of job loss for RA patients with inadequate response to MTX or TNFi.

Potential health gains for patients with metastatic renal cell carcinoma in daily clinical practice: A real-world cost-effectiveness analysis of sequential first- and second-line treatments.

INTRODUCTION: Randomised controlled trials have shown that targeted therapies like sunitinib are effective in metastatic renal cell carcinoma (mRCC). Little is known about the current use of these therapies, and their associated costs and effects in daily clinical practice. We estimated the real-world cost-effectiveness of different treatment strategies comprising one or more sequentially administered drugs. METHODS: Analyses were performed using patient-level data from a Dutch population-based registry including patients diagnosed with primary mRCC from January 2008 to December 2010 (i.e., treated between 2008 and 2013). The full disease course of these patients was estimated using a patient-level simulation model based on regression analyses of the registry data. A healthcare sector perspective was adopted; total costs included healthcare costs related to mRCC. Cost-effectiveness was expressed in cost per life-year and cost per quality-adjusted life-year (QALY) gained. Probabilistic sensitivity analysis was conducted to estimate the overall uncertainty surrounding cost-effectiveness. RESULTS: In current daily practice, 54% (336/621) of all patients was treated with targeted therapies. Most patients (84%; 282/336) received sunitinib as first-line therapy. Of the patients receiving first-line therapy, 30% (101/336) also received second-line therapy; the majority was treated with everolimus (40%, 40/101) or sorafenib (28%, 28/101). Current treatment practice (including patients not receiving targeted therapy) led to 0.807 QALYs; mean costs were €58,912. This resulted in an additional €105,011 per QALY gained compared to not using targeted therapy at all. Forty-six percent of all patients received no targeted therapy; of these patients, 24% (69/285) was eligible for sunitinib. If these patients were treated with first-line sunitinib, mean QALYs would improve by 0.062-0.076 (where the range reflects the choice of second-line therapy). This improvement is completely driven by the health gain seen amongst patients eligible to receive sunitinib but did not receive it, who gain 0.558-0.684 QALYs from sunitinib. Since additional costs would be €7,072-9,913, incremental costs per QALY gained are €93,107-111,972 compared to current practice. DISCUSSION: Health can be gained if more treatment-eligible patients receive targeted therapies. Moreover, it will be just as cost-effective to treat these patients with sunitinib as current treatment practice.

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.

Outcomes and Drug Costs of Sunitinib Regimens for Metastatic Renal Cell Carcinoma: A Provincial Population-Based Study.

BACKGROUND: Conventional sunitinib dosing in metastatic renal cell carcinoma (mRCC) administers 50 mg daily on a 4 weeks on/2 weeks off (4/2) schedule. Not all patients tolerate this regimen and many undergo modifications to schedule, dose, or both. MATERIAL AND METHODS: All patients with mRCC treated with sunitinib by the Saskatchewan Cancer Agency between January 1, 2006, and January 1, 2013, were included. Regimens were categorized as standard intermittent dosing (SID), modified intermittent schedule (MIS), modified intermittent dosing (MID), combination of modified schedule and dosing (MSD), or continuous dosing (CD). The primary objective was to compare overall survival (OS) between regimens. Secondary outcomes included progression-free survival (PFS), discontinuation due to adverse effects (AE), and medication cost. RESULTS: Among 161 patients, 18.0%, 51.6%, and 30.4% had favorable, intermediate, and poor Heng risk prognoses, respectively. A total of 140 (87.0%) received sunitinib as first-line therapy. MID was associated with longer OS compared with SID (estimated median 28.4 vs. 11.2 months). PFS was longer for MID, MSD, and CD compared with SID (estimated median 12.0, 9.0, and 8.0 months vs. 3.0 months, respectively). Adjustment for potential confounders did not negate these associations. SID also had higher average monthly drug costs than MIS, MID, and MSD. Overall discontinuation rate due to AE was high (24%). CONCLUSION: An adjusted-dose sunitinib regimen is associated with improved OS and PFS over SID, with lower costs. The development of toxicities requiring dose reductions serves as a predictive biomarker for better outcomes.

Analysis of the cost-effectiveness of using vonoprazan-amoxicillin-clarithromycin triple therapy for first-line Helicobacter pylori eradication.

BACKGROUND: Vonoprazan (VPZ)-based triple therapy has been reported to have greater efficacy than a proton pump inhibitor (PPI)-based triple therapy for Helicobacter pylori (H. pylori) eradication. However, because VPZ is more expensive than PPIs such as rabeprazole (RPZ), economic evaluation is essential. METHODS: We performed a retrospective study on 209 patients who underwent first-line eradication of H. pylori infection in Fuyoukai Murakami Hospital from 1 March 2015 to 31 March 2016. Patients who received VPZ, amoxicillin (AMPC) and clarithromycin (CAM) were assigned to the VPZ/AC group (n = 111) and patients who received RPZ, AMPC and CAM to the RPZ/AC group (n = 98). We compared the patients' backgrounds, including age, gender, use of high-dose CAM, past history of peptic ulcer, smoking and drug-related adverse events between the two groups. We defined cost as direct medical costs per patient and effectiveness as the first-line eradication rate in the intention-to-treat (ITT) analysis and analyzed the cost-effectiveness using the cost-effectiveness ratio (CER) and incremental cost-effectiveness ratio (ICER). RESULTS: There was no significant difference in the patients' backgrounds. The ITT analysis revealed an eradication rate of 94.6% for VPZ/AC and 86.7% for RPZ/AC. VPZ/AC cost 1155.4 Japanese yen (JPY) higher than RPZ/AC (34063.4 vs. 32908.0, JPY). CER of VPZ/AC was less than that of RPZ/AC (360.1 vs. 379.4, JPY per percent) and ICER of VPZ/AC was 147.0 JPY (1.28 Euro (EUR), 1 EUR =115 JPY) per percent. CONCLUSIONS: VPZ/AC was more cost-effective than RPZ/AC as first-line therapy for H. pylori eradication.