Initiation of Somatostatin analogues for neuroendocrine tumor patients: a cost-effectiveness analysis.

BACKGROUND & AIMS: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous neoplasms. Although some have a relatively benign and indolent natural history, others can be aggressive and ultimately fatal. Somatostatin analogues (SSAs) improve both quality of life and survival for these patients once they develop metastatic disease. However, these drugs are costly and their cost-effectiveness is not known. METHODS: A decision-analytic model was developed and analyzed to compare two treatment strategies for patients with Stage IV GEP-NETs. The first strategy had all patients start SSA immediately while the second strategy waited, reserving SSA initiation until the patient showed signs of progression. Sensitivity analysis was performed to explore model parameter uncertainty. RESULTS: Our model of patients age 60 with metastatic GEP-NETs suggests empiric initiation of SSA led to an increase 0.62 unadjusted life-years and incremental increase in quality-adjusted life years (QALYs) of 0.44. The incremental costs were $388,966 per QALY and not cost-effective at a willingness-to-pay threshold of $100,000. Death was attributed to GEP-NETs for 94.1% of patients in the SSA arm vs. 94.9% of patients in the DELAY SSA arm. Sensitivity analysis found that the model was most sensitive to costs of SSAs. Using probabilistic sensitivity analysis, the SSA strategy was only cost-effective 1.4% of the time at a WTP threshold of $100,000 per QALY. CONCLUSIONS: Our modeling study finds it is not cost-effective to initiate SSAs at time of presentation for patients with metastatic GEP-NETs. Further clinical studies are needed to identify the optimal timing to initiate these drugs.

Pharmacological Acromegaly Treatment: Cost-Utility and Value of Information Analysis.

OBJECTIVES: To conduct a cost-utility analysis comparing drug strategies involving octreotide, lanreotide, pasireotide, and pegvisomant for the treatment of patients with acromegaly who have failed surgery, from a Brazilian public payer perspective. METHODS: A probabilistic cohort Markov model was developed. One-year cycles were employed. The patients started at 45 years of age and were followed lifelong. Costs, efficacy, and quality of life parameters were retrieved from the literature. A discount rate (5%) was applied to both costs and efficacy. The results were reported as costs per quality-adjusted life year (QALY), and incremental cost-effectiveness ratios (ICERs) were calculated when applicable. Scenario analyses considered alternative dosages, discount rate, tax exemption, and continued use of treatment despite lack of response. Value of information (VOI) analysis was conducted to explore uncertainty and to estimate the costs to be spent in future research. RESULTS: Only lanreotide showed an ICER reasonable for having its use considered in clinical practice (R$ 112,138/US$ 28,389 per QALY compared to no treatment). Scenario analyses corroborated the base-case result. VOI analysis showed that much uncertainty surrounds the parameters, and future clinical research should cost less than R$ 43,230,000/US$ 10,944,304 per year. VOI also showed that almost all uncertainty that precludes an optimal strategy choice involves quality of life. CONCLUSIONS: With current information, the only strategy that can be considered cost-effective in Brazil is lanreotide treatment. No second-line treatment is recommended. Significant uncertainty of parameters impairs optimal decision-making, and this conclusion can be generalized to other countries. Future research should focus on acquiring utility data.

Cost-Effectiveness of Initial Versus Delayed Lanreotide for Treatment of Metastatic Enteropancreatic Neuroendocrine Tumors.

BACKGROUND: The Controlled Study of Lanreotide Antiproliferative Response in Neuroendocrine Tumors (CLARINET) trial showed prolonged progression-free survival in patients initially treated with lanreotide versus placebo. We evaluated the cost-effectiveness of upfront lanreotide versus active surveillance with lanreotide administered after progression in patients with metastatic enteropancreatic neuroendocrine tumors (NETs), both of which are treatment options recommended in NCCN Clinical Practice Guidelines in Oncology for Neuroendocrine and Adrenal Tumors. METHODS: We developed a Markov model calibrated to the CLARINET trial and its extension. We based the active surveillance strategy on the CLARINET placebo arm. We calculated incremental cost-effectiveness ratios (ICERs) in dollars per quality-adjusted life-year (QALY). We modeled lanreotide's cost at $7,638 per 120 mg (average sales price plus 6%), used published utilities (stable disease, 0.77; progressed disease, 0.61), adopted a healthcare sector perspective and lifetime time horizon, and discounted costs and benefits at 3% annually. We examined sensitivity to survival extrapolation and modeled octreotide long-acting release (LAR) ($6,183 per 30 mg). We conducted one-way, multiway, and probabilistic sensitivity analyses. RESULTS: Upfront lanreotide led to 5.21 QALYs and a cost of $804,600. Active surveillance followed by lanreotide after progression led to 4.84 QALYs and a cost of $590,200, giving an ICER of $578,500/QALY gained. Reducing lanreotide's price by 95% (to $370) or 85% (to $1,128) per 120 mg would allow upfront lanreotide to reach ICERs of $100,000/QALY or $150,000/QALY. Across a range of survival curve extrapolation scenarios, pricing lanreotide at $370 to $4,000 or $1,130 to $5,600 per 120 mg would reach ICERs of $100,000/QALY or $150,000/QALY, respectively. Our findings were robust to extensive sensitivity analyses. The ICER modeling octreotide LAR is $482,700/QALY gained. CONCLUSIONS: At its current price, lanreotide is not cost-effective as initial therapy for patients with metastatic enteropancreatic NETs and should be reserved for postprogression treatment. To be cost-effective as initial therapy, the price of lanreotide would need to be lowered by 48% to 95% or 27% to 86% to reach ICERs of $100,000/QALY or $150,00/QALY, respectively.

The effects of pre-operative somatostatin analogue therapy on treatment cost and remission in acromegaly.

PURPOSE: To investigate the effects of preoperative somatostatin analogue (SSA) treatment on the annual cost of all acromegaly treatment modalities and on remission rates. METHODS: The medical records of 135 patients with acromegaly who were followed at endocrinology clinic of Cerrahpasa Medical Faculty for at least 2 years after surgery between 2009 and 2016 were reviewed. RESULTS: The mean follow-up time was 50.9 ± 25.7 months. Early remission was defined according to 3rd month values in patients who didn't achieve remission, and 6th month values in patients who achieved remission at the 3rd month after surgery. The early and late remission rates of the entire study population were 40% and 80.7%, respectively. The early remission of the preoperative SSA-treated group (61.5%) was significantly higher than SSA-untreated group (31.2%) (p = 0.002). The early remission of the preoperative SSA-treated patients with macroadenomas (52.2%) was also significantly higher than the SSA-untreated group (23.5%) (p = 0.02). In the subgroup analysis; this difference was much more pronounced in invasive macroadenomas (p = 0.002). There were no differences between the groups in terms of late remission.The median annual cost of all acromegaly treatment modalities in study population was €3788.4; the cost for macroadenomas was significantly higher than for microadenomas (€4125.0 vs. €3226.5, respectively; p = 0.03). Preoperative SSA use in both microadenomas and macroadenomas didn't alter the cost of treatment. The increase in the duration of preoperative medical treatment had no effect on early or late remissions (p = 0.09; p = 0.8). CONCLUSIONS: Preoperative medical treatment had no effect on the costs of acromegaly treatment. There was a benefical effect of pre-operative SSA use on early remission in patients with macroadenomas; however, this effect didn't persist long term.

Pasireotide for the Prevention of Pancreatic Fistula Following Pancreaticoduodenectomy: A Cost-effectiveness Analysis.

OBJECTIVE: To determine the cost-effectiveness of perioperative administration of pasireotide for reduction of pancreatic fistula (PF). SUMMARY: PF is a major complication following pancreaticoduodenectomy (PD), associated with significant morbidity and healthcare-related costs. Pasireotide is a novel multireceptor ligand somatostatin analogue, which has been demonstrated to reduce the incidence of PF following pancreas resection; however, the drug cost is significant. This study sought to estimate the cost-effectiveness of routine administration of pasireotide to patients undergoing PD, compared with no intervention from the perspective of the hospital system. METHODS: A decision-analytic model was developed to compare costs for perioperative administration of pasireotide versus no pasireotide. The model was populated using an institutional database containing all PDs performed 2002 to 2012 at a single institution, including data regarding clinically significant PF (International Study Group on Pancreatic Fistula Grade B or C) and hospital-related inpatient costs for 90 days following PD, converted to 2014 $USD. Relative risk of PF associated with pasireotide was estimated from the published literature. Deterministic and probabilistic sensitivity analyses were performed to test robustness of the model. RESULTS: Mean institutional cost of index admissions was $67,417 and $31,950 for patients with and without PF, respectively. Pasireotide was the dominant strategy, associated with savings of $1685, and a mean reduction of 1.5 days length of stay. Univariate sensitivity analyses demonstrated cost-savings down to a PF rate of 5.6%, up to a relative risk of PF of 0.775, and up to a drug cost of $2817. Probabilistic sensitivity analysis showed 79% of simulations were cost saving. CONCLUSIONS: Pasireotide appears to be a cost-saving treatment following PD across a wide variation of clinical and cost scenarios.

The Cost of Postoperative Pancreatic Fistula Versus the Cost of Pasireotide: Results from a Prospective Randomized Trial.

OBJECTIVE: The objective of this study was to determine the costs of clinically significant postoperative pancreatic fistula (POPF) and to evaluate the cost-effectiveness of routine pasireotide use. SUMMARY OF BACKGROUND DATA: We recently completed a prospective randomized trial that demonstrated an 11.7% absolute risk reduction of clinically significant POPF with use of perioperative pasireotide in patients undergoing pancreaticoduodenectomy or distal pancreatectomy [POPF: pasireotide (n = 152), 9% vs placebo (n = 148), 21%; P = 0.006]. METHODS: An institutional modeling system was utilized to obtain total direct cost estimates from the 300 patients included in the trial. This system identified direct costs of hospitalization, physician fees, laboratory tests, invasive procedures, outpatient encounters, and readmissions. Total direct costs were calculated from the index admission to 90 days after resection. Costs were converted to Medicare proportional dollars (MP$). RESULTS: Clinically significant POPF occurred in 45 of the 300 randomized patients (15%). The mean total cost for all patients was MP$23,400 (MP$8,000 - MP$202,500). The mean cost for those who developed clinically significant POPF was MP$39,700 (MP$13,800 - MP$202,500) versus MP$20,500 (MP$8,000 - MP$62,900) for those who did not (P = 0.001). The mean cost of pasireotide within the treatment group (n = 152) was MP$3,300 (MP$300 - MP$3,800). The mean cost was lower in the pasireotide (n = 152) group than the placebo (n = 148) group; however, this did not reach statistical significance (pasireotide, MP$22,800 vs placebo, MP$23,900: P = 0.571). CONCLUSIONS: The development of POPF nearly doubled the total cost of pancreatic resection. In this randomized trial, the routine use of pasireotide significantly reduced the occurrence of POPF without increasing the overall cost of care.

Prophylactic pasireotide administration following pancreatic resection reduces cost while improving outcomes.

BACKGROUND AND OBJECTIVES: Pasireotide decreases leak rates after pancreatic resection, though significant drug cost may be prohibitive. We conducted a cost-effectiveness analysis to determine whether prophylactic pasireotide possesses a reasonable cost profile. METHODS: A cost-effectiveness model compared pasireotide administration after pancreatic resection versus usual care, populated by probabilities of clinical outcomes from a randomized trial and hospital costs (2013 US$) from a university pancreatic disease center. Sensitivity analyses were performed to identify influential clinical components of the model. RESULTS: With the cost of pasireotide included, per patient costs of pancreatectomy, including those for readmission, were lower in the intervention arm (41,769 versus 42,159$; net savings of 390$, or 1%). This was associated with a 56% reduction in pancreatic fistula/pancreatic leak/abscess (PF/PL/A; 21.9-9.2%). Pasireotide cost would need to increase by over 15.4% to make the intervention strategy more costly than usual care. Sensitivity analyses exploring variability of key model inputs demonstrated that the three strongest drivers of cost were (i) cost of pasireotide; (ii) probability of readmission; and (iii) probability of PF/PL/A. CONCLUSIONS: Prophylactic pasireotide administration following pancreatectomy is cost savings, reducing expensive post-operative sequealae (major complications and readmissions). Pasireotide should be utilized as a cost-saving measure in pancreatic resection. J. Surg. Oncol. 2016;113:784-788. © 2016 Wiley Periodicals, Inc.

Cost-effectiveness comparison of prophylactic octreotide and pasireotide for prevention of fistula after pancreatic surgery.

PURPOSE: Postoperative pancreatic fistula (POPF) is a major determinant of pancreatic surgery outcome, and prevention of POPF is a relevant clinical challenge. The aim of the present study is to compare the cost-effectiveness of octreotide and pasireotide for POPF prophylaxis. METHODS: A systematic literature review and meta-analysis and a retrospective patient cohort provided the data. Cost-effectiveness was calculated by the incremental cost-effectiveness ratio (ICER) and by decision tree modelling of hospital stay duration. RESULTS: Six randomised trials on octreotide (1255 patients) and one trial on pasireotide (300 patients) were included. The median POPF incidence without prophylaxis was 19.6 %. The relative risks for POPF after octreotide or pasireotide prophylaxis were 0.54 or 0.45. Octreotide prophylaxis (21 × 0.1 mg) costs were 249.69 Euro, compared with 728.84 Euro for pasireotide (14 × 0.9 mg) resulting in an ICER of 266.19 Euro for an additional 1.8 % risk reduction with pasireotide. Decision tree modelling revealed no significant reduction of median hospital stay duration if pasireotide was used instead of octreotide. CONCLUSION: Prophylactic octreotide is almost as effective as pasireotide but incurs significantly fewer drug costs per case. However, the data quality is limited, because the effect of octreotide on clinically relevant POPF is unclear. Together with the lack of multicentric data on pasireotide and its effectiveness, a current off-label use of pasireotide does not appear to be justified.

Multi-modal management of acromegaly: a value perspective.

PURPOSE: The Acromegaly Consensus Group recently released updated guidelines for medical management of acromegaly patients. We subjected these guidelines to a cost analysis. METHODS: We conducted a cost analysis of the recommendations based on published efficacy rates as well as publicly available cost data. The results were compared to findings from a previously reported comparative effectiveness analysis of acromegaly treatments. Using decision tree software, two models were created based on the Acromegaly Consensus Group's recommendations and the comparative effectiveness analysis. The decision tree for the Consensus Group's recommendations was subjected to multi-way tornado analysis to identify variables that most impacted the value analysis of the decision tree. RESULTS: The value analysis confirmed the Consensus Group's recommendations of somatostatin analogs as first line therapy for medical management. Our model also demonstrated significant value in using dopamine agonist agents as upfront therapy as well. Sensitivity analysis identified the cost of somatostatin analogs and growth hormone receptor antagonists as having the most significant impact on the cost effectiveness of medical therapies. CONCLUSION: Our analysis confirmed the value of surgery as first-line therapy for patients with surgically accessible lesions. Surgery provides the greatest value for management of patients with acromegaly. However, in accordance with the Acromegaly Consensus Group's recent recommendations, somatostatin analogs provide the greatest value and should be used as first-line therapy for patients who cannot be managed surgically. At present, the substantial cost is the most significant negative factor in the value of medical therapies for acromegaly.

A cost analysis of somatostatin use in the prevention of pancreatic fistula after pancreatectomy.

BACKGROUND: Studies have shown that somatostatin reduces the occurrence of postoperative pancreatic fistula. However, no study to date has analyzed the cost effectiveness of this treatment. The purpose of this study was to analyze the cost effectiveness of prophylactic somatostatin use with respect to pancreatectomy. METHODS: Review of prospectively collected 2002 patient hepato-pancreatico-biliary database from January 2007 to May 2012. Patients received somatostatin prophylactically at the discretion of their surgeon. Data were analyzed using univariate analysis to determine if somatostatin had an effect on imaging costs, lab costs, "other" costs, PT/OT costs, surgery costs, room and board costs, and total hospital costs. RESULTS: A total of 179 patients underwent pancreatectomy at a single teaching institution. Median total hospital costs were 90,673.50 (59,979-743,667) for patients who developed a postoperative pancreatic fistula versus 86,563 (39,190-463,601) for those who did not (p = 0.004). Median total hospital costs were 89,369 (39,190-743,667) for patients who were administered somatostatin versus 85,291 (40,092-463,601) for patients who did not (p = 0.821). CONCLUSIONS: Pancreatic fistulas significantly increase hospital costs, and somatostatin has been shown to decrease the rate of pancreatic fistula formation. Somatostatin has no significant effect on hospital costs.

Aggressive tumors and difficult choices in acromegaly.

PURPOSE: The current article looks at some of the factors associated with pituitary adenomas displaying unusually aggressive biological and clinical behaviour in patients with acromegaly. METHODS: This was a retrospective, narrative review of previously published evidence chosen at the authors' discretion and presented from the perspective of a Latin American case study. FINDINGS AND CONCLUSIONS: Although most pituitary tumors in acromegalic patients are benign and non-aggressive many can behave more aggressively, compromising local surrounding structures. These lesions tend to respond poorly to somatostatin analogs, have a higher risk of recurrence after surgery and, thus, a worse prognosis. Patients with more aggressive tumors constitute a particular challenge, as they often require several therapeutic approaches and may be difficult to manage, especially when options are restricted due to limited resources.

Randomized, placebo-controlled study of the efficacy of preoperative somatostatin administration in the prevention of postoperative complications following pancreaticoduodenectomy.

BACKGROUND/AIMS: This randomized, placebo-controlled trial was analyzed in order to compare different methods of somatostatin administration in postoperative pancreatic fistula (POPF) and other postoperative complications following pancreaticoduodenectomy (PD). METHODOLOGY: Patients were randomized to a control group (n=32) and an experimental group (n=35). The primary endpoint was the incidences of POPF and other postoperative complications. The definition of POPF was classified as described by the International Study Group of Pancreatic Surgery. In the experimental group, the initial somatostatin was infused 1 day before operation and continued for 7 days after surgery. RESULTS: The incidences of POPF did not show a significant difference between the 2 groups (11/30, 36.7% vs. 14/30, 46.7%; p>0.385). However, blood transfusion volume was 1.7±1.53U in the experimental group and 2.7±2.2U in the control group (p=0.034). Furthermore, the abdominal amylase concentration was significantly lower in the experimental group (p=0.038 and p=0.043, respectively) in both Postoperative Day (POD) 3 and POD 7. CONCLUSIONS: Preoperative prophylactic use of somatostatin cannot decrease the incidence of POPF and other complications after PD compared to postoperative use. However, the amylase concentration of the abdominal drainage and the blood transfusion volume seems to be decreased. Further experimental investigations are needed to estimate the value of preoperative use of somatostatin and clear the concrete mechanism.

Costs of treatment change following first-line somatostatin analog monotherapy among patients with neuroendocrine tumors.

BACKGROUND: This study describes treatment characteristics and healthcare costs prior to and following treatment change from somatostatin analog (SSA) monotherapy among a privately-insured NET patient population in the US. METHODS: Patients with newly diagnosed NET and treated with SSA monotherapy were retrospectively identified in IBM MarketScan claims between 1/1/2014 and 3/31/2019. NET treatment change was captured ≥30 days after the SSA start date (earliest new treatment = index date). Healthcare costs (reimbursed amount in 2019 dollars) were reported for 1, 3, and 6 months pre- and post-index intervals. RESULTS: A total of 305 patients were identified (mean age: 58 years; female: 52%; metastatic disease: 49%). Most patients started on octreotide (81%) vs. lanreotide (19%). Common treatment changes included alternate SSA (38%), targeted therapy (30%), or chemotherapy (23%). Total costs increased on average by $13,272 between the month preceding and following treatment change (p < .001), with the highest increase among patients changing to targeted therapy ($19,677, p < .001) vs. an alternate SSA ($10,240, p < .001) or chemotherapy ($4,057, p = .155). The trajectory in mean cost difference using a 1, 3, and 6-month time period followed an increasing trend for patients who changed to targeted therapy (Δ$19,677, Δ$34,856, Δ$58,387) but was flat for patients who changed to the alternate SSA (Δ$10,240, Δ$10,026, Δ$11,727). CONCLUSIONS: Higher total healthcare costs were observed following treatment change from first-line SSA. Switching to the alternate SSA was associated with a fixed, one-time cost; whereas, switching to targeted therapy was associated with both an initial switching cost and a persistent monthly increase.

Cost-Utility of Acromegaly Pharmacological Treatments in a French Context.

Objective: Efficacy of pharmacological treatments for acromegaly has been assessed in many clinical or real-world studies but no study was interested in economics evaluation of these treatments in France. Therefore, the objective of this study was to estimate the cost-utility of second-line pharmacological treatments in acromegaly patients. Methods: A Markov model was developed to follow a cohort of 1,000 patients for a lifetime horizon. First-generation somatostatin analogues (FGSA), pegvisomant, pasireotide and pegvisomant combined with FGSA (off label) were compared. Efficacy was defined as the normalization of insulin-like growth factor-1 (IGF-1) concentration and was obtained from pivotal trials and adjusted by a network meta-analysis. Costs data were obtained from French databases and literature. Utilities from the literature were used to estimate quality-adjusted life year (QALY). Results: The incremental cost-utility ratios (ICUR) of treatments compared to FGSA were estimated to be 562,463 € per QALY gained for pasireotide, 171,332 € per QALY gained for pegvisomant, and 186,242 € per QALY gained for pegvisomant + FGSA. Pasireotide seems to be the least cost-efficient treatment. Sensitivity analyses showed the robustness of the results. Conclusion: FGSA, pegvisomant and pegvisomant + FGSA were on the cost-effective frontier, therefore, depending on the willingness-to-pay for an additional QALY, they are the most cost-effective treatments. This medico-economic analysis highlighted the consistency of the efficiency results with the efficacy results assessed in the pivotal trials. However, most recent treatment guidelines recommend an individualized treatment strategy based on the patient and disease profile.

Patient Characteristics, Diagnostic Delays, Treatment Patterns, Treatment Outcomes, Comorbidities, and Treatment Costs of Acromegaly in China: A Nationwide Study.

Purpose: Acromegaly is a rare, intractable endocrine disease. We aimed to describe the patient characteristics, diagnostic delays, treatment patterns, treatment outcomes, comorbidities and treatment costs of acromegaly in China. Methods: This is a nationwide cross-sectional study. Patients diagnosed with and treated for acromegaly between 1996 and 2019 across China were surveyed via the Chinese Association of Patients with Acromegaly platform. Results: In total, 473 patients (58.8% females, mean age at diagnosis: 39.4±9.5 years) were included. The median disease duration was 3 years. The most common symptoms were extremity enlargement (91.8%) and facial changes (90.1%). Overall, 63.0% of patients experienced diagnostic delays within healthcare systems; 63.8% of the delays were <1 year. The most common first-line therapy was surgery with a transsphenoidal (76.1%) or transcranial approach (3.2%). Somatostatin analogues or dopamine agonists were administered in 20.5% of the patients as first-line therapies and in 41.7% as adjuvant therapies. Radiotherapy was performed in 32.1% of patients, 99.3% of whom received radiotherapy as an adjuvant therapy. After a median 5-year follow-up, 46.2% achieved biochemical control. Comorbidities were reported in 88.2% of the patients at follow-up; memory deterioration and thyroid nodules were the most common. Controlled patients had greater improvements in symptoms and comorbidities during follow-up than uncontrolled patients. The annual per-capita cost-of-treatment was $11013 in 2018, with medical treatments being the largest contributor (67%). Medical insurance covered 47.2% of all treatment costs. Conclusion: This study provides the first comprehensive description of real-world acromegaly data in China, serving as a basis for future population-based studies.

Cost-effectiveness analysis of second-line pharmacological treatment of acromegaly in Spain.

Objective: To estimate the cost-effectiveness of second-line pharmacological treatments in patients with acromegaly resistant to first-generation somatostatin analogues (FG SSA) from the Spanish National Health System (NHS) perspective.Methods: A Markov model was developed to analyze the cost-effectiveness of pegvisomant and pasireotide in FG SSA-resistant acromegaly, simulating a cohort of patients from the treatment beginning to death. Treatment with pegvisomant or pasireotide was compared to FG SSA retreatment. Efficacy data were obtained from clinical trials and utilities from the literature. Direct health costs were obtained from Spanish sources (€2018).Results: The Incremental Cost Effectiveness Ratio (ICER) of pegvisomant vs. FG SSA was €85,869/Quality-adjusted life years (QALY). The ICER of pasireotide vs. FG SSA was €551,405/QALY. The ICER was mainly driven by the incremental efficacy (4.41 QALY for pegvisomant vs. FG SSA and 0.71 QALY for pasireotide vs. FG SSA), with a slightly lower increase in costs with pegvisomant (€378,597 vs. FG SSA) than with pasireotide (€393,151 vs. FG SSA).Conclusion: The ICER of pasireotide compared to FG SSA was six times higher than the ICER of pegvisomant vs. FG SSA. Pegvisomant is a more cost-effective alternative for the treatment of acromegaly in FG SSA-resistant patients in the Spanish NHS.

A Budget Impact Model of the Addition of Telotristat Ethyl Treatment to the Standard of Care in Patients with Uncontrolled Carcinoid Syndrome.

BACKGROUND: Carcinoid syndrome, a rare condition in patients with neuroendocrine tumours, characterised by flushing and diarrhoea, severely affects patients' quality of life. The current carcinoid syndrome standard of care includes somatostatin analogues, but some patients experience uncontrolled symptoms despite somatostatin analogue therapy. Telotristat ethyl is a novel treatment approved by the European Medicines Agency (EMA) and US FDA that significantly reduces bowel movement frequency in patients with uncontrolled carcinoid syndrome. OBJECTIVE: We developed a model to evaluate the 5-year budget impact of introducing telotristat ethyl to standard care in Swedish patients with uncontrolled carcinoid syndrome. METHODS: Treatment response in the 12-week phase III TELESTAR trial (NCT01677910) informed telotristat ethyl efficacy; subsequently, health states were captured by a Markov model using 4-week cycles. TELESTAR open-label extension data informed telotristat ethyl discontinuation. The number of treatment-eligible patients was estimated from literature reviews reporting the prevalence, incidence and mortality of carcinoid syndrome. A Swedish database study informed real-world costs related to carcinoid syndrome and carcinoid heart disease costs. Telotristat ethyl market share was assumed to increase annually from 24% (year 1) to 70% (year 5). RESULTS: Over the 5-year model horizon, 44 patients were expected to initiate telotristat ethyl treatment. The cumulative net budget impact of adding telotristat ethyl to current standard of care was €172,346; per-year costs decreased from €66,495 (year 1) to €29,818 (year 5). Increased drug costs from adding telotristat ethyl were offset by reduced costs elsewhere. CONCLUSIONS: The expected budget impact of adding telotristat ethyl to the standard of care in Sweden was relatively low, largely because of the rarity of carcinoid syndrome.

Cost-Effectiveness and Efficacy of a Novel Combination Regimen in Acromegaly: A Prospective, Randomized Trial.

CONTEXT: Combination therapy with somatostatin receptor ligand (SRL) plus pegvisomant for patients with acromegaly is recommended after a maximizing dose on monotherapy. Lower-dose combination regimens are not well studied. OBJECTIVE: To compare cost-effectiveness and efficacy of 3 lower-dose combination regimens in controlled and uncontrolled acromegaly. DESIGN AND SETTING: Prospective, randomized, open-label, parallel arm study at a tertiary referral pituitary center. PATIENTS: Adults with acromegaly regardless of response to prior SRL and biochemical control status at baseline, stratified by an SRL dose required for insulin-like growth factor (IGF)-I normalization during any 3-month period within 12 months preceding enrollment. INTERVENTION: Combination therapy for 24 to 32 weeks on arm A, high-dose SRL (lanreotide 120 mg/octreotide long-acting release [LAR] 30 mg) plus weekly pegvisomant (40-160 mg/week); arm B, low-dose SRL (lanreotide 60 mg/octreotide LAR 10 mg) plus weekly pegvisomant; or arm C, low-dose SRL plus daily pegvisomant (15-60 mg/day). MAIN OUTCOME MEASURE: Monthly treatment cost in each arm in participants completing ≥ 24 weeks of therapy. RESULTS: Sixty patients were enrolled and 52 were evaluable. Fifty of 52 (96%) demonstrated IGF-I control regardless of prior SRL responsiveness (arm A, 14/15 [93.3%]; arm B, 22/23 [95.7%]; arm C, 14/14 [100%]). Arm B was least costly (mean, $9837 ±â€…1375 per month), arm C was most expensive (mean, $22543 ±â€…11158 per month), and arm A had an intermediate cost (mean, $14261 ±â€…1645 per month). Approximately 30% of patients required pegvisomant dose uptitration. Rates of adverse events were all < 10%. CONCLUSIONS: Low-dose SRL plus weekly pegvisomant represents a novel dosing option for achieving cost-effective, optimal biochemical control in patients with uncontrolled acromegaly requiring combination therapy.

Burden of Carcinoid Heart Disease in Patients With Carcinoid Syndrome Initiating Somatostatin Analogues.

PURPOSE: As a result of overproduction of serotonin, patients with uncontrolled carcinoid syndrome (CS) may develop carcinoid heart disease (CaHD). However, the prevalence and health care resources to manage CaHD are not well understood. This study investigated the prevalence and economic burden of CaHD among adults with CS in the United States. METHODS: This retrospective study analyzed insurance claims of patients with CS initiating somatostatin analogue (SSA) therapy. Eligible patients had ≥1 medical claim for CS with continuous insurance coverage for 1 year before and at least 30 days after initiating SSA therapy. Markers for CaHD were identified using a predetermined list of medical and/or procedural claims based on the clinical experience of a practicing cardiologist. Case subjects had a documented medical/procedural claim for a marker of CaHD during the study period; control subjects had no markers for CaHD. Baseline characteristics were assessed during the pre-SSA treatment initiation period. Economic outcomes (health care resources and expenditures) were assessed in the follow-up period after SSA treatment initiation and compared between incident case subjects and control subjects. Descriptive statistics were used to assess demographic and clinical characteristics. Univariate and multivariate models were used to assess differences in health care resource use and costs between case subjects and control subjects. FINDINGS: A total of 654 patients met the eligibility criteria; 248 (38%) had a prevalent marker of CaHD and were excluded from the economic analysis. The analytic sample included 406 patients with CS, 185 (46%) of whom had an incident CaHD marker (case subjects) and 221 were controls. Baseline characteristics between the case subjects and control subjects were similar with the exception that case subjects tended to be older. Average health care resource use and costs were higher among case subjects (total costs, $51,825 vs $29,068; P < 0.01), driven by average hospital admissions (1.4 vs 0.7) with increased length of stay (4.3 vs 2.0 days), office visits (22.8 vs 19.8), and outpatient services (22.3 vs 15.4; all, P < 0.05). IMPLICATIONS: CaHD may be common among patients with CS before initiating SSA therapy and within 2 years of starting SSA therapy, suggesting suboptimal control of serotonin production. Patients with CaHD incur substantial economic costs in addition to the clinical morbidity compared with patients with CS and no CaHD.