Il trattamento di pazienti con sepsi grave mediante drotrecogin alfa: una valutazione economica con riferimento all’Italia

Sepsis can be defined as a spectrum of clinical conditions caused by the immune response of a host to infection or trauma and characterized by systemic inflammation and coagulation. Particularly in elderly, immunocompromised and critically ill patients, sepsis is a major cause of morbidity and mortality in intensive care units (ICUs) worldwide. In the US, sepsis is the leading cause of death in noncoronary ICU patients. Drotrecogin alfa, or recombinant human activated protein C, has antithrombotic, antiinflammatory, and profibrinolytic properties. Recently in a phase III trial (PROWESS), Drotrecogin alfa demonstrated significantly reduced mortality in severe sepsis patients at 28 days. In this trial important value factors for the assessment of costs and outcomes of severe sepsis were also considered. The purpose of the present study is to determine the economic burden of the treatment with Drotrecogin alfa, according to a cost-effectiveness analysis based on the data of the PROWESS trial. The study has been adapted to the italian health environment. As regards to the costs per surviving patient and costs per QALY (Quality Adjusted Life Year), the predicted cost-effectiveness ratio of drotrecogin alfa in severe sepsis patients is much lower than the standard values considered as acceptable in the international litterature.

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New and Emerging Therapies for Sepsis

Annals of Pharmacotherapy ◽

10.1345/aph.1a283 ◽

2002 ◽

Vol 36 (4) ◽

pp. 648-654 ◽

Cited By ~ 37

Author(s):

Daniel P Healy

Keyword(s):

Severe Sepsis ◽

Inflammatory Response ◽

Protein C ◽

Drotrecogin Alfa ◽

Activated Protein C ◽

Antibody Fragment ◽

Phase Iii ◽

Human Form ◽

Risk Of Death ◽

Phase Iii Trials

OBJECTIVE: To review the recent advances related to the pathophysiology of sepsis and the rationale for recombinant human-activated protein C (drotrecogin alfa) and other antisepsis agents currently in Phase III trials. DATA SOURCES: A MEDLINE (1990–December 2001) search was performed to identify pertinent literature on the pathophysiology of sepsis and treatment strategies. The search was supplemented with AdisInsight (Adis International) using the search terms sepsis, severe sepsis, or septic shock combined with agents in Phase II or higher clinical development. Abstracts presented at infectious diseases and critical care meetings were also reviewed. STUDY SELECTION AND DATA EXTRACTION: Clinical efficacy studies were selected for drotrecogin alfa and other Phase III investigational agents. DATA SYNTHESIS: Our current understanding of the pathophysiology of sepsis underscores the contribution of increased coagulation and diminished fibrinolytic activity working in conjunction with an excessive and dysregulated inflammatory response. The loss of homeostatic balance among these systems results in a systemic inflammatory response with generalized coagulopathy, microvascular thrombosis, and, ultimately, acute organ failure and death. As a result of these advances, several compounds are now in various phases of development. A recombinant human form of endogenous activated protein C (drotrecogin alfa) was recently approved by the Food and Drug Administration for severe sepsis in adults who have a high risk of death. It possesses anticoagulant, profibrinolytic, and antiinflammatory properties. Other compounds currently in Phase III trials include tissue-factor pathway inhibitor, tumor-necrosis factor antibody fragment, platelet-activating factor acetylhydrolase, antithrombin III, and pyridoxylated hemoglobin polyoxyethylene. CONCLUSIONS: With the recent approval of drotrecogin alfa, there is renewed optimism that we can effectively reduce sepsis-associated mortality.

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PIN30 COST-EFFECTIVENESS ANALYSIS OF DROTRECOGIN ALFA (ACTIVATED; DAA) AS A TREATMENT FOR SEVERE SEPSIS WITH MULTIPLE ORGAN FAILURE (MOF) IN POLAND

Value in Health ◽

10.1016/s1098-3015(10)66475-3 ◽

2008 ◽

Vol 11 (6) ◽

pp. A438

Author(s):

J Kuzma ◽

P Kawalec ◽

P Bochenski

Keyword(s):

Severe Sepsis ◽

Cost Effectiveness ◽

Multiple Organ Failure ◽

Organ Failure ◽

Drotrecogin Alfa ◽

Multiple Organ ◽

Cost Effectiveness Analysis ◽

Effectiveness Analysis ◽

Drotrecogin Alfa Activated

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Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis

50 Studies Every Intensivist Should Know ◽

10.1093/med/9780190467654.003.0010 ◽

2018 ◽

pp. 61-67

Author(s):

Anna M. Ward ◽

Richard M. Pino

Keyword(s):

Severe Sepsis ◽

Study Design ◽

Protein C ◽

Clinical Case ◽

Activated Protein C ◽

Efficacy And Safety ◽

Prowess Trial ◽

Study Intervention ◽

Prowess Study

This chapter provides a summary of the landmark study known as the PROWESS Study. Does treatment with DAA reduce the rate of death from any cause among patients with severe sepsis? Starting with that question, it describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case. The PROWESS trial demonstrated a mortality benefit for DAA among patients with severe sepsis. However, the subsequent ADDRESS, RESOLVE, and PROWESS-SHOCK trials did not demonstrate a benefit of the medication, thus calling the results of PROWESS into question.

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Cost-effectiveness evaluation of abiraterone in the treatment of patients with castration-resistant prostate cancer who previously received docetaxel.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e15107 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e15107-e15107

Author(s):

Akhil Chopra ◽

Stefan Gluck ◽

Alberto J. Montero ◽

Kiran Kumar Venkata Raja Avancha ◽

Gilberto Lopes

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Cost Effectiveness ◽

Incremental Cost ◽

Survival Data ◽

Drug Acquisition ◽

Phase Iii ◽

Sensitivity Analyses ◽

Life Years ◽

The Us

e15107 Background: Treatment with abiraterone improves overall survival (OS), time to prostate-specific antigen progression and radiologic progression-free survival when added to prednisone and best supportive care in patients with advanced castrate-resistant prostate cancer (CRPC) who previously received docetaxel. Little is known about its cost-effectiveness in the United States. Methods: In order to raise awareness of pharmacoeconomics concepts and inform policy-makers in the US, this study aimed to assess the cost-effectiveness of abiraterone in the treatment of advanced CRPC patients, from a payer perspective. We created a decision-analytical model using clinical data from the pivotal phase III trial: COU-AA-301. Health utilities were derived from the available literature. Costs for drug acquisition, physician visits and laboratory tests were obtained from the Center for Medicare Services Drug Payment Table and Physician Fee Schedule and are represented in 2011 US dollars. Life-years saved (LY), Quality-adjusted life years (QALY) and Incremental Cost Effectiveness Ratio (ICER) were calculated using updated survival data presented at the 2011 ASCO meeting. Other main scenarios used the original median survival data published in the New England Journal of Medicine article and adjusted median OS to represent an overall survival hazard ratio of .66. Sensitivity analyses were performed using the confidence intervals for median OS in the pivotal study as well as by halving or doubling all other model inputs. No discounting was used due to the short time-horizon. Results: Abiraterone added 0.38 LY and 0.30 QALY with an incremental cost of $39,320 and therefore a cost of $102,600/LY and an ICER of $129,000/QALY. The main drivers of the model were drug acquisition cost, median OS, and health utility values. The results of the model were robust in different scenarios and sensitivity analyses. Conclusions: Using commonly accepted willingness-to-pay thresholds, such as those suggested by the World Health Organization, treatment of patients with advanced CRPC patients with abiraterone is likely to be cost-effective in the US.

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Cost-effectiveness of nab-paclitaxel plus gemcitabine versus erlotinib plus gemcitabine in metastatic pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.353 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 353-353 ◽

Cited By ~ 1

Author(s):

E. Gabriela Chiorean ◽

Scott Whiting ◽

Gary Binder ◽

George Dranitsaris ◽

Victoria Manax

Keyword(s):

Pancreatic Cancer ◽

Cost Effectiveness ◽

Cost Effective ◽

Phase Iii ◽

Metastatic Pancreatic Cancer ◽

Payer Perspective ◽

The Us ◽

Recent Phase ◽

Cost Effective Alternative ◽

The Cost

353 Background: In a recent phase III trial nab-paclitaxel (albumin-bound paclitaxel) + gemcitabine (nab-P/G) demonstrated a 1.8 month, or 27%, improvement in median overall survival (OS) (HR = 0.72, P < 0.001) vs gemcitabine (G) in first-line metastatic pancreatic cancer (mPC). nab-P/G had higher 1 year OS (35% vs 22%) and improved PFS by 1.8 months (HR = 0.69, P < 0.01). nab-P/G is the first taxane based therapy to show a significant OS improvement in a phase III mPC trial. Erlotinib + gemcitabine (E/G) has also demonstrated activity in mPC, with a 0.3 month OS benefit vs G (HR = 0.82, P = 0.04), a 1 year OS of 23% vs 17%, and 0.2 months PFS benefit (HR = 0.77, P = 0.004) vs G. A cost-effectiveness analysis measuring the cost per life year (LY) gained for nab-P/G and E/G was conducted from the US payer perspective. Methods: Costs and clinical outcomes were evaluated fromnab-P/G vs G and E/G vs G trials of mPC. Health care resource use and the management of grade III/IV adverse events (AE) were collected from a large multisite US oncology clinic, expert opinion, and literature (2012 US dollars). Drug cost per cycle was multiplied by the median cycles delivered from the trials for nab-P/G and E/G. Results: Duration of therapy was 4 months for nab-P/G vs 3.9 months for E/G. Total cost for nab-P/G was $24,984 vs $23,044 for E/G, including drug, administration and AE management. AE costs were similar between the two therapies (Table). Differences of > 5% were noted in neutropenia (rates: nab-P/G = 33%; E/G = 24%), neuropathy (nab-P/G = 17%; E/G = 1%), and rash (nab-P/G = 0%; E/G = 6%). The net survival advantage for nab-P/G vs E/G was 1.5 incremental life months gained. Nab-P/G was cost-effective relative to E/G, at a cost of $15,522 per incremental life year gained. Conclusions: nab-P/G is a cost-effective alternative to E/G in mPC, bringing more months of OS at < $16,000 cost per incremental life year gained. [Table: see text]

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Cost-effectiveness of drotrecogin alfa (activated) in the treatment of severe sepsis*

Critical Care Medicine ◽

10.1097/00003246-200301000-00001 ◽

2003 ◽

Vol 31 (1) ◽

pp. 1-11 ◽

Cited By ~ 160

Author(s):

Derek C. Angus ◽

Walter T. Linde-Zwirble ◽

Gilles Clermont ◽

Daniel E. Ball ◽

Bruce R. Basson ◽

...

Keyword(s):

Severe Sepsis ◽

Cost Effectiveness ◽

Drotrecogin Alfa ◽

Drotrecogin Alfa Activated

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PIN18 ASSESSING THE COST-EFFECTIVENESS OF DROTRECOGIN ALFA (ACTIVATED) IN SEVERE SEPSIS IN POLAND

Value in Health ◽

10.1016/s1098-3015(10)66035-4 ◽

2004 ◽

Vol 7 (6) ◽

pp. 763

Author(s):

M Jakubczyk ◽

E Kowalik ◽

M Niewada ◽

A Kübler ◽

J Lis ◽

...

Keyword(s):

Severe Sepsis ◽

Cost Effectiveness ◽

Drotrecogin Alfa ◽

Drotrecogin Alfa Activated ◽

The Cost

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Obesity Does Not Alter the Pharmacokinetics of Drotrecogin Alfa (Activated) in Severe Sepsis

Annals of Pharmacotherapy ◽

10.1345/aph.1e386 ◽

2005 ◽

Vol 39 (2) ◽

pp. 262-267 ◽

Cited By ~ 18

Author(s):

Howard Levy ◽

David Small ◽

Darell E Heiselman ◽

Richard Riker ◽

Jay Steingrub ◽

...

Keyword(s):

Body Weight ◽

Severe Sepsis ◽

Actual Body ◽

Drotrecogin Alfa ◽

Phase Iii ◽

Actual Body Weight ◽

Open Label ◽

Risk Of Death ◽

Drotrecogin Alfa Activated ◽

Significant Difference

BACKGROUND: Drotrecogin alfa (activated) [DrotAA] is approved for the reduction of mortality in adults with severe sepsis (sepsis with acute organ dysfunction) and high risk of death. Patients whose actual body weight was >135 kg were excluded from the Phase III PROWESS trial. OBJECTIVE: To compare exposure to DrotAA in patients with severe sepsis weighing >135 kg with those weighing ⩽135 kg in an open-label, Phase IV trial, and quantify the elimination half-life (t1/2) of DrotAA in these patients. METHODS: PROWESS inclusion/exclusion criteria were used, except that patients >135 kg were enrolled. Blood samples were collected for steady-state plasma concentration (Css) analysis of activated protein C once each day and for t1/2 analysis after infusion. Weight-normalized clearance (Clp) and t1/2 estimates for DrotAA were calculated and compared between weight groups. RESULTS: Patient weight range was 59–227 kg. There were 32 patients ⩽135 kg and 20 patients >135 kg enrolled. Median Clp was 0.45 L/h/kg (interquartile range [IQR] 0.37–0.54) for patients ⩽135 kg and 0.42 L/h/kg (IQR 0.33–0.54) for patients >135 kg (p = 0.692). Median estimates of Css were 51.9 ng/mL (IQR 43.4–62.0) and 56.5 ng/mL (IQR 44.9–71.1; p = 0.570). In patients ⩽135 kg, DrotAA had a median t1/2 of 16.7 minutes (IQR 13.9–20.0) compared with 16.0 minutes (IQR 12.9–19.8) in patients >135 kg (p = 0.767), for a composite median t1/2 of 16.3 minutes (IQR 14.2–18.8). CONCLUSIONS: There is no statistically significant difference in Css concentrations or t1/2 of DrotAA between patients weighing ⩽135 kg and >135 kg. DrotAA should be dosed by actual body weight.

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