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.

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.

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.

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.

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.

An Economic Evaluation of Tofacitinib Treatment in Rheumatoid Arthritis: Modeling the Cost of Treatment Strategies in the United States.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib is approved in the United States for use in adults with moderately to severely active RA and an inadequate response or intolerance to methotrexate. OBJECTIVES: To (a) evaluate, using an economic model, the treatment costs of an RA strategy including tofacitinib, compared with adalimumab, etanercept, certolizumab and tocilizumab biologic RA treatment strategies, which are commonly prescribed in the United States, and (b) assess the economic impact of monotherapy and combination therapy in patients who had an inadequate response to methotrexate therapy (MTX-IR analysis) and to combination therapy in patients who had an inadequate response to a tumor necrosis factor inhibitor (TNF-IR analysis). METHODS: A transparent, Excel-based economic model with a decision-tree approach was developed to evaluate costs over a 1- and 2-year time horizon. The model compared tofacitinib 5 mg twice a day (BID) either as monotherapy or in combination with MTX with similarly labeled biologic therapies. Response to treatment was modeled as American College of Rheumatology (ACR) 20/50/70 response. ACR20 represented clinical response and determined whether patients continued therapy. ACR response rates at 6-month intervals were sourced from prescribing information and safety event rates from a published meta-analysis. Following an adverse event or a lack of response to treatment, it was assumed that 75% of patients switched to the next line of treatment (first to abatacept and then to rituximab). The perspective was that of a U.S. payer. Costs were reported in 2015 U.S. dollars and included drug wholesale acquisition costs, monitoring, drug administration, and treatment for minor and serious adverse events. The patient population eligible for treatment was based on the total number of members (i.e., RA and non-RA) in a payer organization; members with RA treated with biologic therapies were estimated using epidemiological data. Sensitivity analyses were conducted to explore the impact of varying key parameters, including treatment-switching probability, product rebate, major rates of adverse drug reaction, and ACR20 rates, on the model outcomes. RESULTS: Tofacitinib combination therapy after MTX failure was associated with the lowest cost per member per month (PMPM) over a 2-year time frame at $5.53, compared with $6.49 for adalimumab, $6.43 for etanercept, $5.95 for certolizumab, and $5.89 for tocilizumab. Similar savings were observed when all biologics were administered as monotherapy. Tofacitinib combination therapy was also associated with the lower PMPM cost compared with adalimumab combination therapy in the TNF-IR analysis. Tofacitinib was also among the lowest cost per ACR20 responder in each analysis. Sensitivity analyses demonstrated that tofacitinib would potentially be cost saving even in the least optimistic scenarios. CONCLUSIONS: This analysis suggests that tofacitinib 5 mg BID following MTX failure is a lower cost per patient treatment option when used either as monotherapy or combination therapy, compared with adalimumab, etanercept, certolizumab and tocilizumab biologic regimens. Tofacitinib + MTX in TNF-IR patients was also predicted to be a lower-cost treatment option compared with adalimumab+MTX and was associated with the lowest cost per ACR 20/50/70 responder. DISCLOSURES: This study was funded by Pfizer, which determined the research topic and paid York Health Economics Consortium to develop the analysis and conduct the research. York Health Economics Consortium has received consultancy fees from Pfizer. Gerber, Wallenstein, Mendelsohn, Bourret, Singh, and Moynagh are employees and shareholders of Pfizer. Editorial support was funded by Pfizer and was provided by Claxton, Jenks, and Taylor, who are employees of York Health Economics Consortium. Study concept and design were contributed primarily by Taylor, Jenks, Gerber, and Singh, along with the other authors. Gerber, Moynagh, and Singh collected the data, assisted by Bouret and Mendelsohn; data interpretation was performed by Claxton, Gerber, Bouret, and Mendelsohn. The manuscript was written primarily by Claxton, with assistance from the other authors, and revised by Claxton, Gerber, Bouret, and Mendelsohn, with assistance from the other authors.

Real-World Treatment Patterns and Costs for Patients with Renal Cell Carcinoma Initiating Treatment with Sunitinib and Pazopanib.

BACKGROUND: Sunitinib and pazopanib are among the most prescribed targeted therapies for the systemic management of advanced renal cell carcinoma (RCC), but published cost comparisons between the 2 agents are few and limited by methodological and population differences. Also, sunitinib is administered on a 4-week on/2-week off cycle, and pazopanib is taken continuously. Thus, appropriate use and cost comparisons between the 2 drugs require methodological approaches to account for these differences. One way to accomplish this is to substitute expected for observed days supply. Recognizing the effects of nonrepresentative days supply values is important for assessing real-world treatment patterns and costs. OBJECTIVES: To (a) characterize demographic and clinical characteristics among patients with RCC newly initiating sunitinib or pazopanib, using a large administrative claims dataset; (b) characterize treatment patterns, persistence, and costs for each treatment group; and (c) assess the effect on treatment patterns and costs for sunitinib by substituting 42 days for prescriptions with 28- or 30-day supplies to account for sunitinib's 4-week on/2-week off dosing schedule. METHODS: This was a retrospective cohort study using health care claims data from the Truven MarketScan Research Databases, which include enrollment information and medical and pharmacy claims. Baseline patient demographic and clinical characteristics and treatment patterns (continuation, discontinuation, switching, or interruption; days supply; and persistence) were compared. Health care costs were calculated as mean daily index medication costs and as total, medical, and medication (all-cause and RCC-related) costs over the 12 months post-index period. Inclusion criteria were continuous health plan enrollment between 6 months pre-index and 12 months post-index; no RCC medications 6 months pre-index; ≥ 2 RCC diagnoses within ±180 days of index; and age ≥ 20 years. For demographic and clinical characteristics, treatment patterns, and costs, means (± standard deviations) for continuous data and relative frequencies for categorical data were reported. Chi-square tests or Student t-tests were used to evaluate differences other than costs. A generalized linear model with gamma distribution and log link was used for evaluating costs, controlling for patient demographic and pre-index clinical characteristics, persistence days, and index medication. All statistical tests were 2-tailed with significance set at P < 0.05 for all comparisons except for interactions with significance set at P < 0.10. The effects of substituting 42 days supply for sunitinib prescription records with 28 or 30 days supply were determined. RESULTS: In total, 609 (15.1% of the sunitinib overall sample) sunitinib patients and 183 (8.3% of the pazopanib overall sample) pazopanib patients were included. Demographic and clinical characteristics were similar for each treatment cohort. The persistence periods and number of prescriptions filled were also similar. Without substitution, significant differences were observed between treatment groups in patterns of index medication use (overall P = 0.0409), with fewer patients taking sunitinib continuing treatment than patients taking pazopanib. However, with substitution, treatment patterns differed significantly (overall P = 0.0026), but with more sunitinib patients than pazopanib patients continuing treatment. Without substitution, unadjusted daily mean index medication costs were significantly different for sunitinib ($216) versus pazopanib ($177, P < 0.0001). Substitution of sunitinib days supply eliminated the significant differences in daily index medication costs between treatment groups. The 1-year RCC-related and all-cause medication, medical, and total unadjusted costs were not significantly different between treatment groups, and substitution had no effect on these costs. After adjustment for possible confounding factors, these cost results were similar to those found with unadjusted analyses. CONCLUSIONS: In this study, patients with RCC who were initiating sunitinib and pazopanib had similar demographic and clinical characteristics and drug persistence patterns. The effect of substituting days supply values was demonstrated as an approach to considering differences in dosing cycles. Substitution significantly reduced sunitinib mean daily index medication costs and eliminated or reversed the direction of significant differences in costs between drugs during the persistence period. No significant differences were observed in unadjusted or adjusted 1-year costs. DISCLOSURES: This study was funded and conducted fully by Pfizer. All authors are employees of Pfizer. This work was presented in part as posters at the 2015 Genitourinary Cancers Symposium, of the American Society of Clinical Oncology; Rosen Shingle Creek, Orlando, FL; February 26-28, 2015, and the 20th Annual International Meeting of the International Society for Pharmacoeconomics and Outcomes Research; Philadelphia, PA; May 16-20, 2015. All authors contributed to study concept and design and to data interpretation. Mardekian was primarily responsible for data collection, along with Harnett. MacLean and Harnett worked on the manuscript, which was revised by MacLean and Mardekian.

Health Care Costs Among Renal Cancer Patients Using Pazopanib and Sunitinib.

Publications that aim to assess the economics of different therapies are important because they complement clinical trial data and may aid in decision making. We therefore read with interest the study by Hansen et al. in the January 2015 issue of JMCP. This study compared  costs between pazopanib (PAZ) and sunitinib (SU) in the first-line treatment of patients with metastatic renal cell carcinoma (mRCC).1 The authors assessed health care costs through assignment of costs from the Truven Health MarketScan Databases to the self-reported health care resource utilization (HCRU) data from the population studied in the phase III noninferiority clinical trial COMPARZ (Pazopanib versus sunitinib in metastatic renal cell carcinoma).2 We are writing to comment on the conclusions drawn from the results presented, the methodology used, and to request additional information and clarification on data presented.

Cost-Effectiveness of Pazopanib Versus Sunitinib for Renal Cancer in the United States.

We write to comment on a recently published study by Delea et al. in the January 2015 issue of JMCP that evaluated the cost-effectiveness (CE) of sunitinib (SU) versus pazopanib (PAZ) as first-line treatment for metastatic renal cell carcinoma (mRCC) from a U.S. third-party payer perspective.1 This analysis was based on COMPARZ and PISCES, clinical trials that compared SU and PAZ2,3 and led the authors to conclude that PAZ is cost-effective (in fact, dominant, according to the base-case results) compared with SU. Such assessment of economic value is clearly important for deciding between therapies to ensure fair access; therefore, we welcome a comparative evaluation of SU and PAZ. However, we believe that some of the key assumptions and inputs used in the model by Delea et al. render their results and conclusions invalid.  Best practice requires that results from a health economic model should reflect the most likely outcomes based on sound methodology and robust evidence for its inputs, as recommended by the International Society of Pharmacoeconomics and Outcomes Research (ISPOR).4 Here, we focus on 2 key areas (utilities and survival modeling) where, in our view, the analysis by Delea et al. falls short of this standard, and a third area (treatment costs) where the basis for the data derived is unclear.

Health care costs among renal cancer patients using pazopanib and sunitinib.

BACKGROUND: Pazopanib was noninferior to sunitinib in progression-free survival in a phase III, open-label, randomized clinical trial comparing the efficacy and safety of the 2 drugs for treatment of patients with advanced renal cell carcinoma (RCC). A secondary analysis of this trial conducted on patient-reported health care resource utilization (HCRU) endpoints revealed significantly fewer monthly telephone consultations and emergency department visits among patients treated with pazopanib over the first 6 months of treatment. OBJECTIVES: To (a) compare total costs of HCRU and adverse events (AEs) in patients with advanced RCC receiving first-line pazopanib or sunitinib from the phase III clinical trial and (b) perform a post hoc economic analysis that applied direct medical care and pharmacy unit costs, obtained from the Truven Health MarketScan Databases, to HCRU and AE rates. METHODS: Total HCRU costs included components for provider contacts, diagnostics, hospitalizations, procedures, and study/nonstudy drugs. Patients were stratified by the presence or absence of an AE in order to estimate costs attributable to AEs. Costs were adjusted to 2013 U.S. dollars. The highest 1% of cost outliers were equally excluded from each group. Univariate (t-test and Kaplan-Meier sample average [KMSA]) and multivariate (using treatment group and region as covariates) analyses were performed. RESULTS: A total of 906 patients (pazopanib, n = 454; sunitinib, n = 452) reported HCRU; higher rates were observed for sunitinib. In unadjusted cost analyses, the mean total costs for pazopanib-treated patients were 8.0% lower than those treated with sunitinib ($80,464 vs. $86,886; P = 0.20). The difference in KMSA-estimated costs was significantly higher for sunitinib versus pazopanib ($156,128 vs. $143,585; P = 0.003). Adjusted cost differences between arms consistently suggested higher costs for sunitinib. Among patients who experienced greater than or equal to 1 AE, costs were $8,118 higher for pazopanib-treated patients and $14,343 for sunitinib-treated patients. CONCLUSIONS: The findings suggest that health care costs were lower among patients with advanced RCC treated first-line with pazopanib versus sunitinib.