The effectiveness and cost-effectiveness of treatments for idiopathic pulmonary fibrosis: systematic review, network meta-analysis and health economic evaluation

BMC Clinical Pharmacology

Athol Wells²  Claudia Bausewein⁶  Sally Singh¹  Katherine MA O’Reilly⁴  Jeremy Jones⁵  Andy J Clegg⁵  David A Scott³  Jill L Colquitt⁵  Vicky R Copley⁵  Emma Loveman⁵ 

[1] University Hospitals of Leicester NHS Trust, Leicester, UK;Green Lane Hospital, London, UK;Icon PLC, Oxford, UK;Mater Misericordiae University Hospital, Dublin, Ireland;Southampton Health Technology Assessments Centre (SHTAC), University of Southampton, Southampton, UK;Department of Palliative Medicine, University Hospital of Munich, Munich, Germany

关键词: Cost-effectiveness;    Meta-analysis;    Systematic review;    Idiopathic pulmonary fibrosis;   

Others  :  1084600
DOI  :  10.1186/2050-6511-15-63

 received in 2014-01-23, accepted in 2014-11-04,  发布年份 2014

【 摘 要 】

Background

Idiopathic pulmonary fibrosis (IPF) is a life-limiting lung disease with considerable impact on patients and carers as the disease progresses. Currently few treatments are available. We aimed to evaluate the clinical and cost-effectiveness of available treatments for IPF.

Methods

Systematic reviews of clinical effectiveness, quality of life and cost effectiveness were undertaken. Eleven bibliographic databases were searched from inception to July 2013 and studies were assessed for eligibility against a set of pre-defined criteria. Two reviewers screened references, extracted data from included studies and appraised their quality. An advisory group was consulted about the choice of interventions. A narrative review was undertaken and where feasible fixed effect and random effects meta-analysis were undertaken including a network meta-analysis (NMA).

A decision-analytic Markov model was developed to estimate cost-effectiveness of pharmacological treatments for IPF. Following best practice recommendations, the model perspective was of the national health service and personal social services, a discount rate of 3.5% for costs and health benefits was applied and outcomes were expressed as cost per quality adjusted life-year gained. Parameter values were obtained from the NMA and systematic reviews. Sensitivity analyses were undertaken.

Results

Fourteen studies were included in the review of clinical effectiveness, of which one evaluated azathioprine, three N-acetylcysteine [NAC] (alone or in combination), four pirfenidone, one nintedanib, one sildenafil, one thalidomide, two pulmonary rehabilitation, and one a disease management programme. Study quality was generally good. Evidence suggests that some effective treatments are available. In NMA only nintedanib and pirfenidone show statistically significant improvements. The model results show increased survival for five pharmacological treatments (NAC triple therapy, inhaled NAC, nintedanib, pirfenidone, and sildenafil) compared with best supportive care, at increased cost. Only inhaled NAC was cost-effective at current willingness to pay thresholds but it may not be clinically effective.

Conclusions

Few interventions have any statistically significant effect and the cost-effectiveness of treatments is uncertain. A lack of studies on palliative care approaches was identified and there is a need for further research into pulmonary rehabilitation and thalidomide in particular. A well conducted RCT on inhaled NAC therapy should also be considered.

【 授权许可】

   
2014 Loveman et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Swigris JJ, Stewart AL, Gould MK, Wilson SR: Patients’ perspectives on how idiopathic pulmonary fibrosis affects the quality of their lives. Health Qual Life Outcomes 2005, 3:61. BioMed Central Full Text
• [2]Meltzer EB, Noble PW: Idiopathic pulmonary fibrosis. Orphanet J Rare Dis 2008, 3:8. http://www.ojrd.com/content/3/1/8 webcite BioMed Central Full Text
• [3]Navaratnam V, Fleming KM, West J, Smith CJ, Jenkins RG, Fogarty A, Hubbard RB: The rising incidence of idiopathic pulmonary fibrosis in the U.K. Thorax 2011, 66:462-467.
• [4]Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G: Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2006, 174:810-816.
• [5]NICE: Diagnosis and management of suspected idiopathic pulmonary fibrosis. CG 163. London: NICE; 2013.
• [6]Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, Lynch DA, Ryu JH, Swigris JJ, Wells AU, Ancochea J, Bouros D, Carvalho C, Costabel U, Ebina M, Hansell DM, Johkoh T, Kim DS, King TE Jr, Kondoh Y, Myers J, Muller NL, Nicholson AG, Richeldi L, Selman M, Dudden RF, et al.: An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011, 183:788-824.
• [7]Christie JD, Edwards LB, Kucheryavaya AY, Benden C, Dipchand AI, Dobbels F, Kirk R, Rahmel AO, Stehlik J, Hertz MI: The registry of the international society for heart and lung transplantation: 29th adult lung and heart-lung transplant report-2012. J Heart Lung Transplant 2013, 31:1073.
• [8]Centre for Reviews and Dissemination: Systematic reviews: CRD’s guidance for undertaking reviews in health care. Third edition. York: York Publishing Services Ltd., CRD; 2009.
• [9]Drummond MF, Jefferson TO: Guidelines for authors and peer reviewers of economic submissions to the BMJ. The BMJ economic evaluation working party. BMJ 1996, 313:275-283.
• [10]Philips Z, Ginnelly L, Sculpher M, Claxton K, Golder S, Riemsma R, Woolacoot N, Glanville J: Review of guidelines for good practice in decision-analytic modelling in health technology assessment. Health Technol Assess 2004, 8:1-158.
• [11]Higgins JP, Green S: Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated march 2011]. Cochrane Collaboration 2011. Available from http://www.cochrane-handbook.org webcite
• [12]Caldwell D, Ades AE, Higgins JPT: Simultaneous comparison of multiple treatments: combining direct and indirect evidence. BMJ 2005, 331:897-900.
• [13]Dias S, Welton NJ, Sutton AJ, Ades AE: NICE DSU technical support document 2: a generalised linear modelling framework for pairwise and network meta-analysis of randomised controlled trials. 2011. http://www.nicedsu.org.uk webcite .14-6-0013
• [14]Chinn S: A simple method for converting an odds ratio to effect size for use in meta-analysis. Stat Med 2000, 19:3127-3131.
• [15]Noble PW, Albera C, Bradford WZ, Costabel U, Glassberg MK, Kardatzke D, King TE Jr, Lancaster L, Sahn SA, Szwarcberg J, Valeyre D, du Bois RM: Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet 2011, 377:1760-1769.
• [16]Richeldi L, Costabel U, Selman M, Kim DS, Hansell DM, Nicholson AG, Brown KK, Flaherty KR, Noble PW, Raghu G, Brun M, Gupta A, Juhel N, Kluglich M, du Bois RM: Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med 2011, 365:1079-1087.
• [17]Hagaman JT, Kinder BW, Eckman MH: Thiopurine S-methyltranferase testing in idiopathic pulmonary fibrosis: a pharmacogenetic cost-effectiveness analysis. Lung 2010, 188:125-132.
• [18]Taniguchi H, Ebina M, Kondoh Y, Ogura T, Azuma A, Suga M, Taguchi Y, Takahashi H, Nakata K, Sato A, Takeuchi M, Raghu G, Kudoh S, Nukiwa T: Pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J 2010, 35:821-829.
• [19]Azuma A, Nukiwa T, Tsuboi E, Suga M, Abe S, Nakata K, Taguchi Y, Nagai S, Itoh H, Ohi M, Sato A, Kudoh S: Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2005, 171:1040-1047.
• [20]Demedts M, Behr J, Buhl R, Costabel U, Dekhuijzen R, Jansen HM, MacNee W, Thomeer M, Wallaert B, Laurent F, Nicholson AG, Verbeken EK, Verschakelen J, Flower CD, Capron F, Petruzzelli S, De Vuyst P, van den Bosch JM, Rodriguez-Becerra E, Corvasce G, Lankhorst I, Sardina M, Montanari M: High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med 2005, 353:2229-2242.
• [21]Raghu G, Anstrom KJ, King J, Lasky JA, Martinez FJ: Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med 2012, 366:1968-1977.
• [22]Homma S, Azuma A, Taniguchi H, Ogura T, Mochiduki Y, Sugiyama Y, Nakata K, Yoshimura K, Takeuchi M, Kudoh S: Efficacy of inhaled N-acetylcysteine monotherapy in patients with early stage idiopathic pulmonary fibrosis. Respirology 2012, 17:467-477.
• [23]Raghu G, Depaso WJ, Cain K, Hammar SP, Wetzel CE, Dreis DF, Hutchinson J, Pardee NE, Winterbauer RH: Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: a prospective double-blind, randomized, placebo-controlled clinical trial. Am Rev Respir Dis 1991, 144:291-296.
• [24]Zisman DA, Schwarz M, Anstrom KJ, Collard HR, Flaherty KR, Hunninghake GW: A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis. N Engl J Med 2010, 363:620-628.
• [25]Horton MR, Santopietro V, Matthew L, Horton KM, Polito AJ, Liu MC, Danoff SK, Lechtzin N: Thalidomide for the treatment of cough in idiopathic pulmonary fibrosis. Ann Intern Med 2012, 157:398-406.
• [26]Nishiyama O, Kondoh Y, Kimura T, Kato K, Kataoka K, Ogawa T, Watanabe F, Arizono S, Nishimura K, Taniguchi H: Effects of pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis. Respirology 2008, 13:394-399.
• [27]Lindell KO, Olshansky E, Song MK, Zullo TG, Gibson KF, Kaminski N, Hoffman LA: Impact of a disease-management program on symptom burden and health-related quality of life in patients with idiopathic pulmonary fibrosis and their care partners. Heart Lung 2010, 39:304-313.
• [28]Jastrzebski D, Kozielski J, Zebrowska A: [Pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis with inspiratory muscle training]. [Polish]. Pneumonol Alergol Pol 2008, 76:131-141.
• [29]Nathan SD, Shlobin OA, Weir N, Ahmad S, Kaldjob JM, Battle E, Sheridan MJ, du Bois RM: Long-term course and prognosis of idiopathic pulmonary fibrosis in the New millennium. Chest 2011, 140:221-229.
• [30]Richeldi L, Ryerson CJ, Lee JS, Wolters PJ, Koth LL, Ley B, Elicker BM, Jones KD, King TE Jr, Ryu JH, Collard HR: Relative versus absolute change in forced vital capacity in idiopathic pulmonary fibrosis. Thorax 2012, 67:407-411.
• [31]Anyanwu AC, McGuire A, Rogers CA, Murday AJ: Assessment of quality of life in lung transplantation using a simple generic tool. Thorax 2001, 56:218-222.
• [32]Department of Health: National health service England and wales electronic drug tariff May 2013. 2013. 14-6-2013. http://www.ppa.org.uk/edt/May_2013/mindex.htm webcite
• [33]Joint Formulary Committee: British national formulary (BNF) 65. No. 65. London: British Medical Association and Royal Pharmaceutical Society of Great Britain; 2013.
• [34]Department of Health: NHS reference costs 2011–2012. https://www.gov.uk/government/publications/nhs-reference-costs-financial-year-2011-to-2012 webcite. 8-11-2012
• [35]Mills EJ, Thorlund K, Ionnidis JPA: Demystifying trial networks and network meta-analysis. BMJ 2013, 346:f2914.