Kosteneffektivität von Pioglitazon bei Patienten mit Typ-2-Diabetes und makrovaskulären Vorerkrankungen in Deutschland

Zusammenfassung

Die mit der Behandlung des Typ-2-Diabetes verbundenen direkten Kosten machen einen erheblichen Anteil der Gesundheitskosten in Deutschland aus, wobei der größte Kostenfaktor die mit dem Diabetes auftretenden Komplikationen sind. Solche Komplikationen durch geeignete Interventionen zu vermeiden ist daher nicht nur unter klinischen, sondern auch unter ökonomischen Gesichtspunkten sinnvoll. In der PROactive-Studie wurde gezeigt, dass Pioglitazon bei Typ-2-Diabetikern mit makrovaskulären Vorerkrankungen das Risiko für weitere kardiovaskuläre Komplikationen reduziert. Auf Basis der Wirksamkeitsdaten der PROactive-Studie wurde inzwischen die Kosteneffektivität von Pioglitazon über 35 Jahre modelliert. Die Ergebnisse dieser gesundheitsökonomischen Analyse wurden kürzlich in der Zeitschrift „Cost Effectiveness and Resource Allocation“ publiziert. Pioglitazon führt über einen Zeitraum von 35 Jahren zu einem Zugewinn von 0,120 qualitätsadjustierten Lebensjahren (QALYs) bei einem zusätzlichen Kostenaufwand von 9281 € pro gewonnenem Lebensjahr und 13 294 € pro gewonnenem QALY. Setzt man die allgemein akzeptierte Bereitschaft voraus, 50 000 € pro gewonnenem QALY zu zahlen, kann Pioglitazon mit einer Wahrscheinlichkeit von 78,2 % als kosteneffektiv angesehen werden. Auf Basis einer Datenbankrecherche wurden Kosteneffektivitätsdaten zu Therapien chronischer Erkrankungen anderer gesundheitsökonomisch relevanter Indikationen ermittelt und diese mit den Ergebnissen zu Pioglitazon in der Therapie des Typ-2-Diabetes verglichen. Es konnte gezeigt werden, dass der Zugewinn an Lebensjahren und QALYs sowie der damit verbundene zusätzliche Kostenaufwand für den Einsatz von Pioglitazon vergleichbar mit den Ergebnissen entsprechender Analysen zum Einsatz von Statinen in der Sekundärprävention und zur antihypertensiven Therapie ist. Gegenüber TNF-alpha-Inhibitoren zur Therapie der rheumatioiden Arthritis ist Pioglitazon kosteneffektiver. 

Abstract

The direct costs associated with the treatment of type 2 diabetes account for a considerable proportion of healthcare costs in Germany, with diabetes-related complications being the biggest cost factor. Therefore avoiding such complications by suitable interventions is a reasonable approach, not only from clinical but also from economic aspects. It was shown in the PROactive study that pioglitazone reduces the risk for further cardiovascular complications in type 2 diabetes patients with a history of macrovascular disease. On the basis of the efficacy data of the PROactive trial, the cost-effectiveness of pioglitazone has meanwhile been modelled over a 35-year period. The results of this health economic analysis were published recently in the journal “Cost Effectiveness and Resource Allocation”. Over a 35-year period treatment with pioglitazone was associated with a gain of 0.120 quality-adjusted life years (QALYs) at an additional cost of € 9281 per life year gained and € 13 294 per QALY gained. Assuming a willingness-to-pay threshold of € 50 000 per QALY gained, there is a 78.2 % likelihood that pioglitazone would be considered cost-effective. On the basis of a database search, cost-effectiveness data on the treatments of chronic diseases from other indications of relevance to healthcare economics were identified and compared with the results for pioglitazone in the treatment of type 2 diabetes. It was shown that the gain in life years and QALYs along with the associated additional cost for the use of pioglitazone is comparable with the results of corresponding analyses on the use of statins in secondary prevention and on anti -hypertensive therapy. Compared with TNF-alpha inhibitors for the treatment of rheumatoid arthritis, pioglitazone is more cost effective. 

Typ-2-Diabetes - Pioglitazon - PROactive - Kosteneffektivität - Gesundheitsökonomie

type 2 diabetes - pioglitazone - PROactive - cost-effectivenes - health economy

Literatur

• 1 Liebl A. [Costs involved in the early and late phases of diabetes mellitus].  Internist (Berl). 2007;  48 708-714
• 2 Liebl A, Neiss A, Spannheimer A et al. [Costs of type 2 diabetes in Germany. Results of the CODE-2 study].  Dtsch Med Wochenschr. 2001;  126 585-589
• 3 Köster I, von Ferber L, Ihle P et al. The cost burden of diabetes mellitus: the evidence from Germany – the CoDiM study.  Diabetologia. 2006;  49 1498-1504
• 4 Köster I, Hauner H, von Ferber L. [Heterogeneity of costs of diabetic patients: the Cost of Diabetes Mellitus Study].  Dtsch Med Wochenschr. 2006;  131 804-810
• 5 Dormandy J A, Charbonnel B, Eckland D J et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial.  Lancet. 2005;  366 1279-1289
• 6 Scherbaum W A, Goodall G, Erny-Albrecht K M et al. Cost-effectiveness of pioglitazone in type 2 diabetes patients with a history of macrovascular disease: a German perspective.  Cost Eff Resour Alloc. 2009;  7 9
• 7 Chiquette E, Ramirez G, Defronzo R. A meta-analysis comparing the effect of thiazolidinediones on cardiovascular risk factors.  Arch Intern Med. 2004;  164 2097-2104
• 8 Schernthaner G. Pleiotropic effects of thiazolidinediones on traditional and non-traditional atherosclerotic risk factors.  Int J Clin Pract. 2009;  63 912-929
• 9 Goldberg R B, Kendall D M, Deeg M A et al. A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia.  Diabetes Care. 2005;  28 1547-1554
• 10 Hanefeld M, Brunetti P, Schernthaner G H et al. One-year glycemic control with a sulfonylurea plus pioglitazone versus a sulfonylurea plus metformin in patients with type 2 diabetes.  Diabetes Care. 2004;  27 141-147
• 11 Derosa G, D’Angelo A, Ragonesi P D et al. Metformin-pioglitazone and metformin-rosiglitazone effects on non-conventional cardiovascular risk factors plasma level in type 2 diabetic patients with metabolic syndrome.  J Clin Pharm Ther. 2006;  31 375-383
• 12 Chappuis B, Braun M, Stettler C et al. Differential effect of pioglitazone (PGZ) and rosiglitazone (RGZ) on postprandial glucose and lipid metabolism in patients with type 2 diabetes mellitus: a prospective, randomized crossover study.  Diabetes Metab Res Rev. 2007;  23 392-399
• 13 Charbonnel B, Schernthaner G, Brunetti P et al. Long-term efficacy and tolerability of add-on pioglitazone therapy to failing monotherapy compared with addition of gliclazide or metformin in patients with type 2 diabetes.  Diabetologia. 2005;  48 1093-1104
• 14 Matthews D R, Charbonnel B H, Hanefeld M et al. Long-term therapy with addition of pioglitazone to metformin compared with the addition of gliclazide to metformin in patients with type 2 diabetes: a randomized, comparative study.  Diabetes Metab Res Rev. 2005;  21 167-174
• 15 Schernthaner G, Matthews D R, Charbonnel B et al. Efficacy and safety of pioglitazone versus metformin in patients with type 2 diabetes mellitus: a double-blind, randomized trial.  J Clin Endocrinol Metab. 2004;  89 6068-6076
• 16 Deeg M A, Buse J B, Goldberg R B et al. Pioglitazone and rosiglitazone have different effects on serum lipoprotein particle concentrations and sizes in patients with type 2 diabetes and dyslipidemia.  Diabetes Care. 2007;  30 2458-2464
• 17 Langenfeld M R, Forst T, Hohberg C et al. Pioglitazone decreases carotid intima-media thickness independently of glycemic control in patients with type 2 diabetes mellitus: results from a controlled randomized study.  Circulation. 2005;  111 2525-2531
• 18 Mazzone T, Meyer P M, Feinstein S B et al. Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial.  JAMA. 2006;  296 2572-2581
• 19 Nissen S E, Nicholls S J, Wolski K et al. Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial.  JAMA. 2008;  299 1561-1573
• 20 Fachinformation actos. 2009
• 21 Matthaei S, Bierwirth R, Fritsche A et al. Medikamentöse antihyperglykämische Therapie des Diabetes mellitus Typ 2 – Update der Evidenzbasierten Leitlinie der Deutschen Diabetes-Gesellschaft.  http://www.deutsche-diabetes-gesellschaft.de 2008
• 22 Erdmann E, Dormandy J A, Charbonnel B et al. The effect of pioglitazone on recurrent myocardial infarction in 2445 patients with type 2 diabetes and previous myocardial infarction: results from the PROactive (PROactive 05) Study.  J Am Coll Cardiol. 2007;  49 1772-1780
• 23 Wilcox R, Bousser M G, Betteridge D J et al. Effects of pioglitazone in patients with type 2 diabetes with or without previous stroke: results from PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events 04).  Stroke. 2007;  38 865-873
• 24 Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen .Glitazone zur Behandlung des Diabetes mellitus Typ 2.  http://www.iqwig.de/download/A05–05A_AB_Glitazone_zur_Behandlung_des_Diabetes_mellitus_Typ_2.pdf 2008
• 25 Brändle M, Goodall G, Erny-Albrecht K M et al. Cost-effectiveness of pioglitazone in patients with type 2 diabetes and a history of macrovascular disease in a Swiss setting.  Swiss Med Wkly. 2009;  139 173-184
• 26 Valentine W J, Bottomley J M, Palmer A J et al. PROactive 06: cost-effectiveness of pioglitazone in Type 2 diabetes in the UK.  Diabet Med. 2007;  24 982-1002
• 27 Valentine W J, Tucker D, Palmer A J et al. Long-term cost-effectiveness of pioglitazone versus placebo in addition to existing diabetes treatment: A US analysis based on PROactive.  Value Health. 2009;  12 1-9
• 28 Palmer A J, Roze S, Valentine W J et al. Validation of the CORE Diabetes Model against epidemiological and clinical studies.  Curr Med Res Opin. 2004;  20 Suppl 1 27-40
• 29 Palmer A J, Roze S, Valentine W J et al. The CORE Diabetes Model: Projecting long-term clinical outcomes, costs and cost-effectiveness of interventions in diabetes mellitus (types 1 and 2) to support clinical and reimbursement decision-making.  Curr Med Res Opin. 2004;  20 Suppl 1 5-26
• 30 Haffner S M, Alexander C M, Cook T J et al. Reduced coronary events in simvastatin-treated patients with coronary heart disease and diabetes or impaired fasting glucose levels: subgroup analyses in the Scandinavian Simvastatin Survival Study.  Arch Intern Med. 1999;  159 2661-2667
• 31 The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group . Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels.  N Engl J Med. 1998;  339 1349-1357
• 32 Goldberg R B, Mellies M J, Sacks F M et al. Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the cholesterol and recurrent events (CARE) trial. The Care Investigators.  Circulation. 1998;  98 2513-2519
• 33 Ward S, Lloyd J M, Pandor A et al. A systematic review and economic evaluation of statins for the prevention of coronary events.  Health Technol Assess. 2007;  11 1-iv
• 34 Zechmeister I, Wild C. Einsatz von Statinen zur Sekundärprävention von kardiovaskulären Erkrankungen – ein systematischer Review gesundheitsökonomischer Analysen.  http://epub.oeaw.ac.at/ita/ita-projektberichte/ 2006
• 35 Obermann K, Graf von der Schulenburg J M, Mautner G C. Ökonomische Aspekte der Sekundärprävention der koronaren Herzkrankheit mit Simvastatin in Deutschland.  Medizinische Klinik. 1997;  92 686-694
• 36 Johannesson M, Jonsson B, Kjekshus J et al. Cost effectiveness of simvastatin treatment to lower cholesterol levels in patients with coronary heart disease. Scandinavian Simvastatin Survival Study Group.  N Engl J Med. 1997;  336 332-336
• 37 Cook J R, Yin D, Alemao E et al. Cost-effectiveness of ezetimibe coadministration in statin-treated patients not at cholesterol goal: application to Germany, Spain and Norway.  Pharmacoeconomics. 2004;  22 Suppl 3 49-61
• 38 Kannel W B. Clinical misconceptions dispelled by epidemiological research.  Circulation. 1995;  92 3350-3360
• 39 Kannel W B, Dannenberg A L, Abbott R D. Unrecognized myocardial infarction and hypertension: the Framingham Study.  Am Heart J. 1985;  109 581-585
• 40 Vasan R S, Beiser A, Seshadri S et al. Residual lifetime risk for developing hypertension in middle-aged women and men: The Framingham Heart Study.  JAMA. 2002;  287 1003-1010
• 41 Gandjour A, Stock S. A national hypertension treatment program in Germany and its estimated impact on costs, life expectancy, and cost-effectiveness.  Health Policy. 2007;  83 257-267
• 42 Montgomery A A, Fahey T, Ben-Shlomo Y et al. The influence of absolute cardiovascular risk, patient utilities, and costs on the decision to treat hypertension: a Markov decision analysis.  J Hypertens. 2003;  21 1753-1759
• 43 Ekman M, Bienfait-Beuzon C, Jackson J. Cost-effectiveness of irbesartan / hydrochlorothiazide in patients with hypertension: an economic evaluation for Sweden.  J Hum Hypertens. 2008;  22 845-855
• 44 Boersma C, Carides G W, Atthobari J et al. An economic assessment of losartan-based versus atenolol-based therapy in patients with hypertension and left-ventricular hypertrophy: results from the Losartan Intervention For Endpoint reduction (LIFE) study adapted to The Netherlands.  Clin Ther. 2007;  29 963-971
• 45 Palmer A J, Roze S, Rodby R A et al. [Clinical and health economic implications of early treatment with irbesartan of patients with type 2 diabetes mellitus, hypertension and nephropathy].  Dtsch Med Wochenschr. 2006;  131 1721-1726
• 46 Kielhorn A, Porter D, Diamantopoulos A et al. UK cost-utility analysis of rituximab in patients with rheumatoid arthritis that failed to respond adequately to a biologic disease-modifying antirheumatic drug.  Curr Med Res Opin. 2008;  24 2639-2650
• 47 Chen Y F, Jobanputra P, Barton P et al. A systematic review of the effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in adults and an economic evaluation of their cost-effectiveness.  Health Technol Assess. 2006;  10 iii-xiii, 1
• 48 Kulp W, Corzillius M, Greiner W et al. Wertigkeit von Tumor-Nekrose-Faktor-alpha-Antagonisten in der Behandlung der Rheumatoiden Arthritis.  http://gripsdb-dimdi-de/de/hta/hta_berichte/hta075_bericht_de.pdf 2005
• 49 Eichler H G, Kong S X, Gerth W C et al. Use of cost-effectiveness analysis in health-care resource allocation decision-making: how are cost-effectiveness thresholds expected to emerge?.  Value Health. 2004;  7 518-528
• 50 Devlin N, Parkin D. Does NICE have a cost-effectiveness threshold and what other factors influence its decisions? A binary choice analysis.  Health Econ. 2004;  13 437-452