A Cost-Effectiveness Analysis of Nintedanib in Idiopathic Pulmonary Fibrosis in the UK

C Rinciog, M Watkins, S Chang, T M Maher, C LeReun, D Esser, A Diamantopoulos, C Rinciog, M Watkins, S Chang, T M Maher, C LeReun, D Esser, A Diamantopoulos

Abstract

Background: International guidelines recommend nintedanib (OFEV®) as an option for the treatment of idiopathic pulmonary fibrosis (IPF).

Objective: The objective of this study was to assess the cost effectiveness of nintedanib versus pirfenidone, N-acetylcysteine and best supportive care (BSC) for the treatment of IPF from a UK payer's perspective.

Methods: A Markov model was designed to capture the changes in the condition of adults with IPF. Efficacy outcomes included mortality, lung function decline and acute exacerbations. Treatment safety (serious adverse events) and tolerability (overall discontinuation) were also considered. The baseline risk of these events was derived from patient-level data from the placebo arms of nintedanib clinical trials (TOMORROW, INPULSIS-1, INPULSIS-2). A network meta-analysis (NMA) was conducted to estimate the relative effectiveness of the comparator treatments. Quality of life and healthcare resource use data from the clinical trials were also incorporated in the economic model.

Results: Nintedanib showed statistically significant differences against placebo on acute exacerbation events avoided and lung function decline. In the cost-effectiveness analysis, the results were split between two treatments with relative low costs and modest effectiveness (BSC and N-acetylcysteine) and two that showed improved effectiveness (lung function) and higher costs (nintedanib and pirfenidone). All comparators were assumed to have similar projected survival and the difference in quality-adjusted life-years (QALYs) was driven by the acute exacerbations and lung function estimates. In the base-case deterministic pairwise comparison with pirfenidone, nintedanib was found to have fewer acute exacerbations and resulted in less costs and more QALYs gained.

Conclusions: Compared with BSC (placebo), nintedanib and pirfenidone were the only treatments to show statistical significance in the efficacy parameters. We found substantial uncertainty in the overall cost-effectiveness results between nintedanib and pirfenidone. N-Acetylcysteine was largely similar to BSC but with a worse survival profile. INPULSIS-1 and INPULSIS-2 ClinicalTrials.gov numbers, NCT01335464 and NCT01335477.

Conflict of interest statement

Funding

This study was funded by Boehringer Ingelheim. Boehringer Ingelheim was involved in the analysis of clinical trial data.

Conflicts of interest

CR, SC and AD are employed by Symmetron Ltd, which received funding from Boehringer Ingelheim for this project. CLR received funding for this project from Symmetron Ltd. TMM has received consulting fees from Symmetron Ltd; industry-academic research funding from GlaxoSmithKline R&D, UCB and Novartis; and consultancy or speakers fees from AstraZeneca, Bayer, Biogen Idec, Boehringer Ingelheim, Cipla, Dosa, Galapagos, GlaxoSmithKline R&D, ProMetic, Roche (and previously InterMune), Sanofi-Aventis, Takeda and UCB. TMM is supported by a National Institute for Health Research (NIHR) Clinician Scientist Fellowship (NIHR ref: CS-2013-13-017). DE is an employee of Boehringer Ingelheim. MW was an employee of Boehringer Ingelheim UK at the time this study was conducted. A copy of the cost-effectiveness model was provided to the journal for external review.

Figures

Fig. 1
Fig. 1
Model structure
Fig. 2
Fig. 2
Comparison of overall survival of the model best supportive care arm with observational data [5, 19]. BSC best supportive care
Fig. 3
Fig. 3
Tornado diagram for nintedanib vs. best supportive care
Fig. 4
Fig. 4
Cost-effectiveness scatter plot. BSC best supportive care, PSA probabilistic sensitivity analysis, QALYs quality-adjusted life-years
Fig. 5
Fig. 5
Multiple cost-effectiveness acceptability curve. BSC best supportive care

References

    1. National Institute for Health and Care Excellence (NICE). Diagnosis and management of suspected idiopathic pulmonary fibrosis. Idiopathic pulmonary fibrosis: full version. National Clinical Guideline Centre (UK). London: Royal College of Physicians; 2013.
    1. Nalysnyk L, Cid-Ruzafa J, Rotella P, Esser D. Incidence and prevalence of idiopathic pulmonary fibrosis: review of the literature. Eur Respir Rev. 2012;21(126):355–361. doi: 10.1183/09059180.00002512.
    1. George TJ, Arnaoutakis GJ, Shah AS. Lung transplant in idiopathic pulmonary fibrosis. Arch Surg. 2011;146(10):1004–1209. doi: 10.1001/archsurg.2011.239.
    1. Idiopathic Pulmonary Fibrosis Clinical Research Network Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med. 2012;366(21):1968–1977. doi: 10.1056/NEJMoa1113354.
    1. Kondoh Y, Taniguchi H, Katsuta T, Kataoka K, Kimura T, Nishiyama O, et al. Risk factors of acute exacerbation of idiopathic pulmonary fibrosis. Sarcoidosis Vasc Diffuse Lung Dis. 2010;27(2):103–110.
    1. Raghu G, Rochwerg B, Zhang Y, Garcia CA, Azuma A, Behr J, et al. An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. An update of the 2011 clinical practice guideline. Am J Respir Crit Care Med. 2015;192(2):e3–e19. doi: 10.1164/rccm.201506-1063ST.
    1. National Institute for Health and Care Excellence (NICE). Final appraisal determination—nintedanib for treating idiopathic pulmonary fibrosis. 2015. . Accessed 29 Nov 2016.
    1. National Institute for Health and Care Excellence (NICE). Final appraisal determination—pirfenidone for treating idiopathic pulmonary fibrosis. 2013. . Accessed 29 Nov 2016.
    1. Scottish Medicines Consortium (SMC). Pirfenidone 267 mg capsule (Esbriet®). InterMune. SMC no. (835/13). 2013. . Accessed 29 Nov 2016.
    1. Scottish Medicines Consortium (SMC). Nintedanib 100 mg and 150 mg capsules (Ofev®). Boehringer Ingelheim. SMC no. (1076/15). 2015. . Accessed 29 Nov 2016.
    1. Richeldi L, Costabel U, Selman M, Kim DS, Hansell DM, Nicholson AG, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011;365(12):1079–1087. doi: 10.1056/NEJMoa1103690.
    1. Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, et al. INPULSIS Trial Investigators. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2071–2082. doi: 10.1056/NEJMoa1402584.
    1. Alakhras M, Decker PA, Nadrous HF, Collazo-Clavell M, Ryu JH. Body mass index and mortality in patients with idiopathic pulmonary fibrosis. Chest. 2007;131(5):1448–1453. doi: 10.1378/chest.06-2784.
    1. Antoniou KM, Hansell DM, Rubens MB, Marten K, Desai SR, Siafakas NM, et al. Idiopathic pulmonary fibrosis: outcome in relation to smoking status. Am J Respir Crit Care Med. 2008;177(2):190–194. doi: 10.1164/rccm.200612-1759OC.
    1. Lederer DJ, Arcasoy SM, Barr RG, Wilt JS, Bagiella E, D’Ovidio F, et al. Racial and ethnic disparities in idiopathic pulmonary fibrosis: a UNOS/OPTN database analysis. Am J Transplant. 2006;6(10):2436–2442. doi: 10.1111/j.1600-6143.2006.01480.x.
    1. Lederer DJ, Arcasoy SM, Wilt JS, D’Ovidio F, Sonett JR, Kawut SM. Six-minute-walk distance predicts waiting list survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2006;174(6):659–664. doi: 10.1164/rccm.200604-520OC.
    1. Lopes AJ, Capone D, Mogami R, Lanzillotti RS, Melo PL, Jansen JM. Severity classification for idiopathic pulmonary fibrosis by using fuzzy logic. Clinics. 2011;66(6):1015–1019. doi: 10.1590/S1807-59322011000600016.
    1. Manali ED, Stathopoulos GT, Kollintza A, Kalomenidis I, Emili JM, Sotiropoulou C, et al. The Medical Research Council chronic dyspnea score predicts the survival of patients with idiopathic pulmonary fibrosis. Respir Med. 2008;102(4):586–592. doi: 10.1016/j.rmed.2007.11.008.
    1. Nathan SD, Shlobin OA, Weir N, Ahmad S, Kaldjob JM, Battle E, et al. Long-term course and prognosis of idiopathic pulmonary fibrosis in the new millennium. Chest. 2011;140(1):221–229. doi: 10.1378/chest.10-2572.
    1. Zappala CJ, Latsi PI, Nicholson AG, Colby TV, Cramer D, Renzoni EA, et al. Marginal decline in forced vital capacity is associated with a poor outcome in idiopathic pulmonary fibrosis. Eur Respir J. 2010;35(4):830–836. doi: 10.1183/09031936.00155108.
    1. du Bois RM, Weycker D, Albera C, Bradford WZ, Costabel U, Kartashov A, et al. Ascertainment of individual risk of mortality for patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;184(4):459–466. doi: 10.1164/rccm.201011-1790OC.
    1. Ley B, Ryerson CJ, Vittinghoff E, Ryu JH, Tomassetti S, Lee JS, et al. A multidimensional index and staging system for idiopathic pulmonary fibrosis. Ann Intern Med. 2012;156(10):684–691. doi: 10.7326/0003-4819-156-10-201205150-00004.
    1. du Bois RM, Weycker D, Albera C, Bradford WZ, Costabel U, Kartashov A, et al. Forced vital capacity in patients with idiopathic pulmonary fibrosis: test properties and minimal clinically important difference. Am J Respir Crit Care Med. 2011;184(12):1382–1389. doi: 10.1164/rccm.201105-0840OC.
    1. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, 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(6):788–824. doi: 10.1164/rccm.2009-040GL.
    1. Idiopathic Pulmonary Fibrosis Clinical Research Network, Martinez FJ, de Andrade JA, Anstrom KJ, King TE Jr, Raghu G. Randomized trial of acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2093–101.
    1. Noble PW, Albera C, Bradford WZ, Costabel U, Glassberg MK, Kardatzke D, et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet. 2011;377(9779):1760–1769. doi: 10.1016/S0140-6736(11)60405-4.
    1. Azuma A, Nukiwa T, Tsuboi E, Suga M, Abe S, Nakata K, et al. Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2005;171(9):1040–1047. doi: 10.1164/rccm.200404-571OC.
    1. Homma S, Azuma A, Taniguchi H, Ogura T, Mochiduki Y, Sugiyama Y, et al. Efficacy of inhaled N-acetylcysteine monotherapy in patients with early stage idiopathic pulmonary fibrosis. Respirology. 2012;17(3):467–477. doi: 10.1111/j.1440-1843.2012.02132.x.
    1. King TE, Jr, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, et al. ASCEND Study Group. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2083–2092. doi: 10.1056/NEJMoa1402582.
    1. Taniguchi H, Ebina M, Kondoh Y, Ogura T, Azuma A, Suga M, et al. Pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J. 2010;35(4):821–829. doi: 10.1183/09031936.00005209.
    1. Tomioka H, Kuwata Y, Imanaka K, Hashimoto K, Ohnishi H, Tada K, et al. A pilot study of aerosolized N-acetylcysteine for idiopathic pulmonary fibrosis. Respirology. 2005;10(4):449–455. doi: 10.1111/j.1440-1843.2005.00725.x.
    1. Ara R, Brazier JE. Using health state utility values from the general population to approximate baselines in decision analytic models when condition-specific data are not available. Value Health. 2011;14(4):539–545. doi: 10.1016/j.jval.2010.10.029.
    1. Curtis L. Unit costs of health and social care 2013. Canterbury: University of Kent; 2013.
    1. Monthly Index of Medical Specialties (MIMS). . Accessed 29 Nov 2016.
    1. National Health Service (NHS). National schedule of reference costs 2012-13 for NHS trusts and NHS foundation trusts (2013). . Accessed 9 Dec 2016.
    1. Electronic Medicines Compendium (eMC). Esbriet 267 mg hard capsules - summary of product characteristics (SPC). . Accessed 29 Nov 2016.
    1. Electronic Medicines Compendium (eMC). Ofev 100 mg and 150 mg soft capsules -Summary of Product Characteristics (SPC). . Accessed 29 Nov 2016.
    1. National Health Service (NHS). National Schedule of Reference Costs 2010-11 for NHS trusts and NHS foundation trusts. (2011). . Accessed 9 Dec 2016.
    1. Hatziandreu E, Archontakis F, Daly A; in conjuction with the National Audit Office. The potential cost savings of greater use of home- and hospice-based end of life care in England. Cambridge: RAND Europe; 2008.
    1. Trawinska MA, Rupesinghe RD, Hart SP. Patient considerations and drug selection in the treatment of idiopathic pulmonary fibrosis. Ther Clin Risk Manag. 2016;12:563–574.
    1. National Institute for Health and Care Excellence (NICE). Guide to the methods of technology appraisal. London: National Institute for Health and Care Excellence; 2013. . Accessed 29 Nov 2016.
    1. Loveman E, Copley VR, Colquitt JL, Scott DA, Clegg AJ, Jones J, et al. The effectiveness and cost-effectiveness of treatments for idiopathic pulmonary fibrosis: systematic review, network meta-analysis and health economic evaluation. BMC Pharmacol Toxicol. 2014;15(63):13.
    1. Wilson EC, Shulgina L, Cahn AP, Chilvers ER, Parfrey H, Clark AB, et al. Treating idiopathic pulmonary fibrosis with the addition of co-trimoxazole: an economic evaluation alongside a randomised controlled trial. Pharmacoeconomics. 2014;32(1):87–99. doi: 10.1007/s40273-013-0112-z.
    1. Shulgina L, Cahn AP, Chilvers ER, Parfrey H, Clark AB, Wilson EC, et al. Treating idiopathic pulmonary fibrosis with the addition of co-trimoxazole: a randomised controlled trial. Thorax. 2013;68(2):155–162. doi: 10.1136/thoraxjnl-2012-202403.
    1. Husereau D, Drummond M, Petrou S, Carswell C, Moher D, Greenberg D, et al. CHEERS Task Force. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. BMJ. 2013;346:f1049. doi: 10.1136/bmj.f1049.
    1. Canestaro WJ, Forrester SH, Raghu G, Ho L, Devine BE. Drug treatment of idiopathic pulmonary fibrosis: systematic review and network meta-analysis. Chest. 2016;149(3):756–766. doi: 10.1016/j.chest.2015.11.013.
    1. Rochwerg B, Neupane B, Zhang Y, Garcia CC, Raghu G, Richeldi L, et al. Treatment of idiopathic pulmonary fibrosis: a network meta-analysis. BMC Med. 2016;14:18. doi: 10.1186/s12916-016-0558-x.
    1. Gutierrez L, Patris J, Hutchings A, Cowell W. Principles for consistent value assessment and sustainable funding of orphan drugs in Europe. Orphanet J Rare Dis. 2015;10:53. doi: 10.1186/s13023-015-0269-y.
    1. Hughes-Wilson W, Palma A, Schuurman A, Simoens S. Paying for the orphan drug system: break or bend? Is it time for a new evaluation system for payers in Europe to take account of new rare disease treatments? Orphanet J Rare Dis. 2012;7:74. doi: 10.1186/1750-1172-7-74.
    1. Cohen JP, Felix A. Are payers treating orphan drugs differently? J Mark Access Health Policy. 2014;2:23513. doi: 10.3402/jmahp.v2.23513.
    1. Thompson SC, Pitts JS, Schwankovsky L. Preferences for involvement in medical decision-making: situational and demographic influences. Patient Educ Couns. 1993;22(3):133–140. doi: 10.1016/0738-3991(93)90093-C.
    1. Haynes RB, Devereaux PJ, Guyatt GH. Clinical expertise in the era of evidence-based medicine and patient choice. Vox Sang. 2002;83(Suppl 1):383–386.
    1. Boehringer Ingelheim. Summary of clinical safety. Nintedanib (BIBF 1120). Ingelheim: Boehringer Ingelheim; 2014. (Data on file).

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