A Real-World Observational Study of the Use and Associated Costs of Treating Neuroendocrine Tumors With Somatostatin Analogs in Canada.

OBJECTIVES: Somatostatin analogs (SSAs; lanreotide autogel and octreotide long-acting release) are used to treat neuroendocrine tumors; however, factors that influence SSA use are unclear. METHODS: This real-world, observational study collected data from private/public pharmacy claims for patients using SSAs in Canada. Data relating to dosing regimens, injection burden, treatment persistence, and costs were retrospectively analyzed for treatment-naive patients. RESULTS: Overall, 1545 patients were included in the analysis of dosing regimens, 908 for injection burden, 453 for treatment persistence, and 903 for treatment-associated costs. Compared with lanreotide, treatment with octreotide long-acting release was more likely associated with treatment above the maximum recommended dose (odds ratio, 16.2; 95% confidence interval, 4.3-136.2; P < 0.0001), higher weighted average long-acting SSA injection burden (13.4 vs 12.5, P < 0.0001), and a higher number of rescue medication claims per patient (0.22 vs 0.03, P < 0.0001). Treatment with lanreotide autogel was associated with greater treatment persistence (hazard ratio, 0.58; 95% confidence interval, 0.42-0.80; P = 0.001) and lower mean annual costs of treatment than octreotide long-acting release (Canadian dollars $27,829.35 vs $31,255.49; P < 0.0001). CONCLUSIONS: These findings provide valuable insight into SSA use in clinical settings and may inform treatment selection.

Monitoramento do horizonte tecnológico: Hemoglobinúria paroxística noturna / Technological Horizon Monitoring: Paroxysmal Nocturnal Hemoglobinuria

A DOENÇA: A Hemoglobinúria Paroxística Noturna (HPN) é uma anemia hemolítica crônica caracterizada por um defeito intrínseco da membrana eritrocitária. A doença se apresenta clinicamente com vários sintomas, entre os quais se destacam a anemia hemolítica e a hemoglobinúria, além de fadiga e falta de ar. O nome da doença decorre da liberação de hemoglobina na urina, sendo notada, principalmente, por coloração marrom-escura na primeira urina da manhã, consequência da destruição de eritrócitos. TRATAMENTO: As opções de tratamento para HPN permaneceram limitadas ao transplante de células-tronco hematopoiéticas e manejo dos sintomáticos e das complicações, até o desenvolvimento do anticorpo monoclonal humanizado eculizumabe. O medicamento é direcionado à proteína C5 da cascata do complemento e impede a lise dos eritrócitos. Assim, a ação do eculizumabe resulta em uma inibição sustentada da hemólise mediada pelo complemento em quase todos os pacientes com HPN11. Novos medicamentos e biossimilares do eculizumabe estão em desenvolvimento, com alvo para diferentes vias de inibição da ação do sistema complemento. ESTRATÉGIA DE BUSCA: As tecnologias novas e emergentes para o tratamento da HPN foram identificadas nas bases de dados Cortellis da Clarivate Analytics (em 16 de novembro de 2020 e atualizada em 13 de setembro de 2021), com filtros para tecnologias em desenvolvimento (fase 2 e 3) e novas (lançados, registrados ou com pré-registro). Posteriormente, foi realizada busca no sítio eletrônico ClinicalTrials.gov (em 22 de dezembro de 2020 e atualizada em 13 de setembro de 2021), utilizando o termo "paroxysmal nocturnal hemoglobinuria" e filtro para as fases 2, 3 e 4 de pesquisa clínica. Além disso, foram consultadas as bases eletrônicas: MEDLINE (via PubMed) em 22 de dezembro de 2020 e atualizado em 10 de setembro de 2021 e EMBASE (via Portal Capes) em 07 de janeiro de 2021 e atualizado em 13 de setembro de 2021, com o termo "paroxysmal nocturnal hemoglobinúria" e seus sinônimos, sendo considerados ensaios clínicos a partir da fase 2. INFORMAÇÕES ADICIONAIS: Os fabricantes cujos medicamentos estão em fase avançada de desenvolvimento para doenças raras, como no caso da HPN, têm apresentado resultados parciais e contínuos aos órgãos sanitários, como EMA e FDA, a fim de iniciar um diálogo visando ao registro do medicamento. Dependendo dos resultados os medicamentos podem obter status de órfão, o que traz alguns benefícios como, por exemplo, taxas reduzidas para pedido de registro e proteção contra concorrência uma vez que esteja aprovado para comercialização91. Assim, foram pesquisados os aspectos regulatórios das tecnologias emergentes e novas identificadas nesse informe. CONCLUSÃO: O prognóstico da hemoglobinúria paroxística noturna vem mudando desde a introdução do primeiro inibidor do complemento C5 (eculizumabe) em 2017, no Brasil. Apesar do benefício clínico que o medicamento trouxe, ainda existe uma parcela da população com HPN que, por diferentes fatores, tem pouca resposta e ainda necessita de transfusões de sangue para o tratamento da anemia. A partir do conhecimento do funcionamento do sistema complemento na HPN e suas vias de ativação, diferentes alvos estão sendo utilizados no desenvolvimento de medicamentos para o tratamento da doença. Tais mecanismos envolvem a inibição de proteínas C3 e C5, fator B e fator D do sistema complemento. Medicamentos novos como o ravulizumabe, já registrado no Brasil desde 2019, e outros emergentes em fases avançadas de desenvolvimento com resultados publicados, se mostram potencialmente eficazes para o controle de marcadores bioquímicos relacionados aos processos hematológicos da HPN, tornando- -se alternativas para o controle da doença. O presente informe traz um panorama das potenciais tecnologias que podem impactar no tratamento da HPN no futuro em relação à comodidade posológica com medicamentos em diferentes vias de administração e resultados promissores nos desfechos para o controle adequado da doença.

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.

Analysis of Real-World Treatment Patterns, Healthcare Resource Utilization, and Costs Between Octreotide and Lanreotide Among Patients With Neuroendocrine Tumors.

OBJECTIVE: The aim of the study was to assess treatment patterns, healthcare resource utilization, and healthcare costs among patients with neuroendocrine tumors (NETs) receiving long-acting octreotide versus lanreotide, overall and in patients with carcinoid syndrome (CS). METHODS: A provider-based claims database was used to identify NET patients who first initiated long-acting octreotide or lanreotide (index date) from January 2015 to November 2017. Propensity-score matching 1:1 was used. Patients with CS were identified from the previously mentioned matched cohorts. Time-to-treatment discontinuation (TTD) was estimated using Kaplan-Meier analyses. Per-patient-per-month rates of healthcare resource utilization were compared using rate ratios from multivariable Poisson regression models. Multivariable linear regression models were used to compare mean monthly cost differences. RESULTS: The median TTD was similar between the 2 matched cohorts (N = 543 each; long-acting octreotide = 19.2 months, lanreotide = 17.5 months, P = 0.58). Significantly fewer NET-related outpatient visits (rate ratio = 0.95, P = 0.005) and significantly lower total healthcare costs (mean monthly cost difference: all-cause = US -$3701, NET-related = US -$3752, Ps < 0.001) were observed in the long-acting octreotide cohort than lanreotide. Similar results were found in CS patients. CONCLUSIONS: Patients on first-line long-acting octreotide and lanreotide had similar TTD. Long-acting octreotide was associated with significantly lower total healthcare costs than lanreotide.

Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement.

The Korean Endocrine Society (KES) published clinical practice guidelines for the treatment of acromegaly in 2011. Since then, the number of acromegaly cases, publications on studies addressing medical treatment of acromegaly, and demands for improvements in insurance coverage have been dramatically increasing. In 2017, the KES Committee of Health Insurance decided to publish a position statement regarding the use of somatostatin analogues in acromegaly. Accordingly, consensus opinions for the position statement were collected after intensive review of the relevant literature and discussions among experts affiliated with the KES, and the Korean Neuroendocrine Study Group. This position statement includes the characteristics, indications, dose, interval (including extended dose interval in case of lanreotide autogel), switching and preoperative use of somatostatin analogues in medical treatment of acromegaly. The recommended approach is based on the expert opinions in case of insufficient clinical evidence, and where discrepancies among the expert opinions were found, the experts voted to determine the recommended approach.

Synthetic Cross-linking of Peptides: Molecular Linchpins for Peptide Cyclization.

Peptide-derived drugs constitute a significant fraction of therapeutic agents. In 2013, The global market of peptide therapeutics was ca. $19 billion; this value does not include revenue from insulin derivatives of $28 million. The combined sales of insulin and non-insulin peptide drugs is estimated to exceed $70 billion by 2019. A significant fraction of peptide-derived drugs is composed of an amino acid sequence and additional chemical functionalities that improve biological and pharmacological properties of the drug. In this review, we focus on synthetic cross-linkers that we refer to as "linchpins", which are commonly used to constrain the secondary structure of peptides and equip them with added benefits such as resistance to proteolytic degradation and conformational stability. The latter property leads to an increase in binding potency and increased bioavailability due to increased permeation through biological membranes. Some linchpins can even introduce properties not found in natural peptides such as light-responsiveness. Peptides cyclized by linchpins can be viewed as a sub-class of a larger family of peptide-derived drugs with desired pharmacological performance in vivo. To understand how chemical modifications by linchpins improve drug discovery, this review also briefly summarizes canonical examples of chemical modification used in modern peptide therapeutics.

Cost-effectiveness of acromegaly treatments: a systematic review.

PURPOSE: Acromegaly is a rare disease that results in the enlargement of body extremities and in organomegaly. Treatments include surgery, drugs, and radiotherapy, which are all onerous. Therefore, well-conducted cost-analyses are crucial in the decision-making process. METHODS: A systematic review of cost-effectiveness studies on acromegaly therapies was performed following PRISMA and Cochrane recommendations. The search for records was conducted in PubMed, Scopus, and Web of Science (May 2018). The quality of the included studies was assessed using the Joana Briggs Institute Tool. RESULTS: From initial 547 records, 16 studies were included in the review. The studies could present more than one economic evaluation, and encompassed cost-effectiveness (n = 13), cost-utility (n = 5), and cost-consequence (n = 1) analyses. All studies were model-based and evaluated only direct medical costs. Eleven records did not mention discounting and only 10 performed sensitivity analyses. The characteristic of the studies, the cost-effectiveness results and the studies' conclusions are described and commented upon. The main limitation of the studies was discussed and aspects to improve in future studies were pointed out. CONCLUSIONS: Cost-effectiveness studies on acromegaly have been performed in several scenarios, evaluating different phases of treatment. However, the studies present limitations and, overall, were considered of moderate quality. Further economic models should be developed following health economics guidelines recommendations, and must improve transparency.

Assessment of the Neuroprotective Effects of Arginine-Rich Protamine Peptides, Poly-Arginine Peptides (R12-Cyclic, R22) and Arginine-Tryptophan-Containing Peptides Following In Vitro Excitotoxicity and/or Permanent Middle Cerebral Artery Occlusion in Rats.

We have demonstrated that arginine-rich and poly-arginine peptides possess potent neuroprotective properties with arginine content and peptide positive charge being particularly critical for neuroprotective efficacy. In addition, the presence of other amino acids within arginine-rich peptides, as well as chemical modifications, peptide length and cell-penetrating properties also influence the level of neuroprotection. Against this background, we have examined the neuroprotective efficacy of arginine-rich protamine peptides, a cyclic (R12-c) poly-arginine peptide and a R22 poly-arginine peptide, as well as arginine peptides containing tryptophan or other amino acids (phenylalanine, tyrosine, glycine or leucine) in in vitro glutamic acid excitotoxicity and in vivo rat permanent middle cerebral artery occlusion models of stroke. In vitro studies demonstrated that protamine and poly-arginine peptides (R12-c, R22) were neuroprotective. Arginine-tryptophan-containing peptides were highly neuroprotective, with R12W8a being the most potent arginine-rich peptide identified in our laboratory. Peptides containing phenylalanine or tyrosine substituted in place of tryptophan in R12W8a were also highly neuroprotective, whereas leucine, and in particular glycine substitutions, decreased peptide efficacy. In vivo studies with protamine administered intravenously at 1000 nmol/kg 30 min after MCAO significantly reduced infarct volume and cerebral oedema by 22.5 and 38.6%, respectively. The R12W8a peptide was highly toxic when administered intravenously at 300 or 100 nmol/kg and ineffective at reducing infarct volume when administered at 30 nmol/kg 30 min after MCAO, unlike R18 (30 nmol/kg), which significantly reduced infarct volume by 20.4%. However, both R12W8a and R18 significantly reduced cerebral oedema by 19.8 and 42.2%, respectively. Protamine, R12W8a and R18 also reduced neuronal glutamic acid-induced calcium influx. These findings further highlight the neuroprotective properties of arginine-rich peptides and support the view that they represent a new class of neuroprotective agent.

Patient-reported outcomes of parenteral somatostatin analogue injections in 195 patients with acromegaly.

BACKGROUND: Long-acting somatostatin analogues delivered parenterally are the most widely used medical treatment in acromegaly. This patient-reported outcomes survey was designed to assess the impact of chronic injections on subjects with acromegaly. METHODS: The survey was conducted in nine pituitary centres in Germany, UK and The Netherlands. The questionnaire was developed by endocrinologists and covered aspects of acromegaly symptoms, injection-related manifestations, emotional and daily life impact, treatment satisfaction and unmet medical needs. RESULTS: In total, 195 patients participated, of which 112 (57%) were on octreotide (Sandostatin LAR) and 83 (43%) on lanreotide (Somatuline Depot). The majority (>70%) of patients reported acromegaly symptoms despite treatment. A total of 52% of patients reported that their symptoms worsen towards the end of the dosing interval. Administration site pain lasting up to a week following injection was the most frequently reported injection-related symptom (70% of patients). Other injection site reactions included nodules (38%), swelling (28%), bruising (16%), scar tissue (8%) and inflammation (7%). Injection burden was similar between octreotide and lanreotide. Only a minority of patients received injections at home (17%) and 5% were self-injecting. Over a third of patients indicated a feeling of loss of independence due to the injections, and 16% reported repeated work loss days. Despite the physical, emotional and daily life impact of injections, patients were satisfied with their treatment, yet reported that modifications that would offer major improvement over current care would be 'avoiding injections' and 'better symptom control'. CONCLUSION: Lifelong injections of long-acting somatostatin analogues have significant burden on the functioning, well-being and daily lives of patients with acromegaly.

Dosage and costs of lanreotide Autogel 120 mg administered as part of routine acromegaly care in Poland - two years of data from Lanro-Study.

INTRODUCTION: To evaluate, over 24 months of prospective follow-up, the dosage and costs of lanreotide AUTOGEL 120 mg (ATG120) administered as part of routine acromegaly care in Poland. MATERIAL AND METHODS: A multicentre, non-interventional, observational prospective study on resource utilisation in Polish acromegalic patients treated with ATG120 at 4-week or extended (> 4 weeks) dosing interval. The study population consisted of adult acromegalic patients treated for at least 3 injections of ATG120. The endpoints were: percentage of patients treated with ATG120 at an extended dosing interval (> 4 weeks), mean time between injections, and the cost of ATG120 during a 24-month prospective observation. Costs were calculated in PLN from the public health-care payer and patient perspective for the year 2014. RESULTS: 143 patients were enrolled in, and 132 completed (70% women, 81% macroadenoma, 75% previous surgery) the analysis. During two years, changes in the treatment pattern were reported in 41 patients: 17% of them had increased injection interval and 10% switched to octreotide LAR and then returned to ATG120. Sixty-three patients (48%) received ATG120 at an extended dosing interval. ATG120 was predominantly administered in an out-patient setting (84%) by a health care professional (97%). CONCLUSIONS: The results demonstrated that extended dosing interval of ATG120 is used in a substantial proportion of patients in routine clinical practice in Poland. Such findings support the potential for ATG120 in reducing treatment burden in the real-world clinical environment.

Development and validation of a polycystic liver disease complaint-specific assessment (POLCA).

BACKGROUND & AIMS: Polycystic liver disease (PCLD) may lead to extensive hepatomegaly and invalidating complaints. Therapeutic decisions, including somatostatin-analogues (SAs) and (non)-transplant surgery are besides the existence of hepatomegaly, also guided by the severity of complaints. We developed and validated a self-report instrument to capture the presence and severity of disease specific complaints for PCLD. METHODS: The study population consisted of 129 patients. Items for the PCLD-complaint-specific assessment (POLCA) were developed based on the chart review of symptomatic PCLD patients (n=68) and literature, and discussed during expert-consensus-meetings. 61 patients who needed therapy were asked to complete the POLCA and the short form health survey version 2 (SF36V2) at baseline and after 6 months of SA-treatment. CT-scans were used to calculate liver volumes (LV). Factor analysis was conducted to identify subscales and remove suboptimal items. Reliability was assessed by Cronbach's alpha. Convergent, criterion validity and responsiveness were tested using prespecified hypotheses. RESULTS: In the validation group (n=61), 47 received lanreotide (LAN) and 14 were offered LAN as bridge to liver transplantation (LTx). Factor analysis identified four subscales, which correlated with the physical component summary (PCS). Baseline POLCA scores were significantly higher in LTx-listed patients. In contrast to SF36V2, POLCA-paired observations in 47 patients demonstrated that 2 subscales were lowered significantly and 2 borderline. LV reduction of ⩾ 120 ml resulted in a numerical, more pronounced relative decrease of all scores. CONCLUSIONS: In contrast to SF36V2, the POLCA shows good validity and responsiveness to measure complaint severity in PCLD.

Clinical, quality of life, and economic value of acromegaly disease control.

Although acromegaly is a rare disease, the clinical, economic and health-related quality of life (HRQoL) burden is considerable due to the broad spectrum of comorbidities as well as the need for lifelong management. We performed a comprehensive literature review of the past 12 years (1998-2010) to determine the benefit of disease control (defined as a growth hormone [GH] concentration <2.5 µg/l and insulin-like growth factor [IGF]-1 normal for age) on clinical, HRQoL, and economic outcomes. Increased GH and IGF-1 levels and low frequency of somatostatin analogue use directly predicted increased mortality risk. Clinical outcome measures that may improve with disease control include joint articular cartilage thickness, vertebral fractures, left ventricular function, exercise capacity and endurance, lipid profile, and obstructive apnea events. Some evidence suggests an association between controlled disease and improved HRQoL. Total direct treatment costs were higher for patients with uncontrolled compared to controlled disease. Costs incurred for management of comorbidities, and indirect cost could further add to treatment costs. Optimizing disease control in patients with acromegaly appears to improve outcomes. Future studies need to evaluate clinical outcomes, as well as HRQoL and comprehensive economic outcomes achieved with controlled disease.

Long-term results of treatment of malignant carcinoid syndrome with prolonged release Lanreotide (Somatuline Autogel).

BACKGROUND: Somatostatin analogues are the mainstay of therapy for malignant carcinoid syndrome. There is clear evidence that the once monthly intramuscular formulation, Octreotide LAR, controls symptoms of carcinoid syndrome, and recent data also suggests an antitumour effect. There is limited data on prolonged release Lanreotide (Somatuline Autogel, Ipsen Pharma Biotech, Signes, France) and no long-term data to date. AIM: To present long-term results of prolonged release Lanreotide in a large cohort of patients with malignant carcinoid syndrome, assessing clinical and objective response and tolerance. METHODS: Seventy six patients with metastatic midgut neuroendocrine tumours and carcinoid syndrome were included in this 9-year retrospective study. Clinical response was based on symptom score with radiological assessment based on RECIST (Response Evaluation Criteria In Solid Tumours). RESULTS: Data were available in 69 patients. Ninety four percent achieved symptomatic response at first follow-up visit. Forty six percent had loss of symptomatic response, but 44% of these achieved control with an increase in dose of prolonged release Lanreotide. Overall, symptoms were well controlled throughout the study period with prolonged release Lanreotide alone in 74% of patients. Twenty six percent required additional treatment despite good initial response. Only 30% demonstrated radiological progression. Eleven patients who were switched from Octreotide LAR had return of symptomatic control. No significant adverse effects were experienced. CONCLUSIONS: Prolonged release Lanreotide provides good symptomatic control of diarrhoea and flushing as well as tumour stability in patients with malignant carcinoid syndrome.

Assessment of voluntary ethanol consumption and the effects of a melanocortin (MC) receptor agonist on ethanol intake in mutant C57BL/6J mice lacking the MC-4 receptor.

BACKGROUND: The melanocortin (MC) system is composed of peptides that are cleaved from the polypeptide precursor proopiomelanocortin (POMC). Recent evidence shows that chronic exposure to ethanol significantly blunts central MC peptide immunoreactivity and MC receptor (MCR) agonists protect against high ethanol intake characteristic of C57BL/6J mice. Here, we assessed the role of the MC-4 receptor (MC4R) in voluntary ethanol intake and in modulating the effects of the nonselective MCR agonist melanotan-II (MTII) on ethanol consumption. METHODS: To assess the role of the MC4R, MC4R knockout (Mc4r(-/-) ) and littermate wild-type (Mc4r(+/+) ) mice on a C57BL/6J background were used. Voluntary ethanol (3, 5, 8, 10, 15, and 20%, v/v) and water intake were assessed using standard two-bottle procedures. In separate experiments, Mc4r(-/-) and Mc4r(+/+) mice were given intracerebroventricular (i.c.v.) infusion of MTII (0, 0.5, or 1.0 µg/1 µl) or intraperitoneal (i.p.) injection of MTII (0 or 5 mg/kg/5 ml). The effects of MTII (0 or 0.5 µg/1 µl, i.c.v.) on 10% sucrose and 0.15% saccharin intake were assessed in C57BL/6J mice. RESULTS: Mc4r(-/-) mice showed normal consumption of ethanol over all concentrations tested. I.c.v. infusion of MTII significantly reduced ethanol drinking in Mc4r(+/+) mice, but failed to influence ethanol intake in Mc4r(-/-) mice. When administered in an i.p. injection, MTII significantly reduced ethanol drinking in both Mc4r(-/-) and Mc4r(+/+) mice. MTII attenuated consumption of caloric (ethanol, sucrose, and food) and noncaloric (saccharin) reinforcers. CONCLUSIONS: When given centrally, the MCR agonist MTII reduced ethanol drinking by signaling through the MC4R. On the other hand, MTII-induced reduction of ethanol drinking did not require the MC4R when administered peripherally. Together, the present observations show that the MC4R is necessary for the central actions of MCR agonists on ethanol drinking and that MTII blunts the consumption natural reinforcers, regardless of caloric content, in addition to ethanol.

Medical therapy of acromegaly in Turkey.

Acromegaly is associated with multiple co-morbidities and risk of premature mortality. Mortality rate of acromegalic patients is similar to that of the general population when normal GH levels are achieved. Surgery is the mainstay of acromegaly but when surgery fails to achieve disease control, or when surgery is impossible or contraindicated, patients are offered medical therapy and/or radiotherapy. Current medical therapy modalities were revised in this short review.

Cost-effectiveness of lanreotide Autogel in treatment algorithms of acromegaly.

The introduction of effective pharmacological treatments has changed the management of acromegaly. However, chronic, life-long treatment with somatostatin analogues and/or growth hormone receptor antagonists is very expensive. We estimated the costs of treatment algorithms to control acromegaly from a Dutch perspective. We used the following assumptions: after the diagnosis of acromegaly there is a mean remaining lifespan of approximately 33 years; the success rates of surgery and somatostatin analogues in controlling the disease are approximately 60%; and the lifelong costs of different algorithms to control acromegaly in 100 patients ranged from 43 million euros (primary surgery and secondary somatostatin analogues) to 57 million euros (primary somatostatin analogues and secondary surgery) and even reached 95 million euros (medical treatment only). In algorithms that include trans-sphenoidal surgery, the lifetime treatment costs are almost 46-59% cheaper per 100 patients than in algorithms with medical treatment but without trans-sphenoidal surgery. Algorithms with primary surgery and secondary somatostatin analogs are 30% cheaper per 100 patients than algorithms with primary somatostatin analogues and secondary surgery. Per 100 patients, algorithms including lanreotide Autogel are 14-34% more expensive than algorithms including octreotide long-acting release. These life-long costs should be taken into consideration when making choices between treatment algorithms.

Cost-effectiveness analysis of somatostatin analogues in the treatment of acromegaly in Brazil / Análise de custo-efetividade de análogos da somatostatina no tratamento de acromegalia no Brasil

This study aims to compare economic and patient impacts of the treatment of acromegaly with two different somatostatin analogues (octreotide LAR and lanreotide SR) in Brazil. A cost-effectiveness analysis was carried out under the Brazilian Public Health Care System (SUS) perspective. A decision analytical model was developed based on the Brazilian Public Health Care System Clinical Guideline for Acromegaly. A hypothetical cohort of 276 patients was followed for two years. Data were extracted from literature and administrative databases. Based on the analytical model, treatment with octreotide LAR would avoid 12 and 17 cases of GH and IGF-I elevated serum levels, respectively. Octreotide LAR was a cost-saving strategy, with net savings of R$10,448,324 (US$4,465,096) to SUS. Annual net savings per patient were R$ 18,928 (US$8,089). Treatment of acromegaly with octreotide LAR is a dominant strategy when compared to the treatment with lanreotide SR in Brazil. Sensitivity analysis did not alter the cost-saving status.

O objetivo deste estudo é comparar o impacto econômico e o impacto nos pacientes com acromegalia do tratamento com dois diferentes análogos de somatostatina (octreotida LAR e lanreotide SR) no Brasil. Um estudo de custoefetividade foi realizado a partir da perspectiva do Sistema Único de Saúde (SUS). Foi desenvolvido um modelo analítico de decisão baseado no Protocolo Clínico e Diretrizes Terapêuticas de Acromegalia do SUS. Uma coorte hipotética de 276 pacientes foi seguida por dois anos. Dados foram obtidos da literatura e bases de dados oficiais do SUS. Baseado no modelo analítico, o tratamento com octreotida LAR evitaria 12 e 17 casos com níveis elevados de GH e IGF-I, respectivamente. Octreotida LAR foi uma estratégia econômica, gerando economia de R$10.448.324 (US$4.465.096) para o SUS. A economia anual por paciente foi de R$18.928 (US$8.089). O tratamento de acromegalia com octreotida LAR é estratégia dominante quando comparado com o tratamento com lanreotida SR no Brasil. A análise de sensibilidade não alterou seu status de econômica.