Skip to main content
Top
Published in: Rheumatology International 9/2017

01-09-2017 | Health Services Research

Cost-utility analysis of certolizumab pegol in combination with methotrexate in patients with moderate-to-severe active rheumatoid arthritis in Greece

Authors: C. Tzanetakos, A. Tzioufas, A. Goules, G. Kourlaba, T. Theodoratou, P. Christou, N. Maniadakis

Published in: Rheumatology International | Issue 9/2017

Login to get access

Abstract

We aimed to evaluate the cost-effectiveness of certolizumab pegol (CZP), a pegylated fc-free anti-TNF, as add-on therapy to methotrexate (MTX) versus etanercept, adalimumab, or golimumab in patients with moderate-to-severe active rheumatoid arthritis (RA) not responding to the conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). A Markov model (6-month cycle length) assessed health and cost outcomes of CZP versus other anti-TNFs recommended for RA in Greece over a patient’s lifetime. Following discontinuation of first-line anti-TNF, patients switched to second anti-TNF and then to a biologic with another mode of action. Sequential use of csDMARDs followed third biologic. Clinical data and utilities were extracted from published literature. Analysis was conducted from third-party payer perspective in Greece. Costs (drug acquisition, administration, monitoring, and patient management) were considered for 2014. Results presented are incremental cost-effectiveness ratios (ICERs) per quality-adjusted life year (QALY). Probabilistic sensitivity analysis (PSA) ascertained robustness of base-case findings. Base-case analysis indicated that CZP+MTX was more costly and more effective compared with Etanercept+MTX (base-case ICER: €3,177 per QALY), whilst versus adalimumab/golimumab, CZP was dominant (less costly, more effective). For all comparisons, CZP treatment resulted in greater improvements in life expectancy and QALYs. PSA indicated that at the willingness-to-pay threshold of €34,000/QALY, CZP+MTX was associated with a 71.6, 97.9, or 99.2% probability of being cost-effective versus etanercept, golimumab, or adalimumab, respectively, in combination with MTX. This analysis demonstrates CZP+MTX to be a cost-effective alternative over Etanercept+MTX and a dominant option over Adalimumab+MTX and Golimumab+MTX for management of RA in Greece.
Literature
1.
go back to reference Pollard L, Choy EH, Scott DL (2005) The consequences of rheumatoid arthritis: quality of life measures in the individual patient. Clin Exp Rheumatol 23(5 Suppl 39):S43–S52PubMed Pollard L, Choy EH, Scott DL (2005) The consequences of rheumatoid arthritis: quality of life measures in the individual patient. Clin Exp Rheumatol 23(5 Suppl 39):S43–S52PubMed
2.
go back to reference Rindfleisch JA, Muller D (2005) Diagnosis and management of rheumatoid arthritis. Am Fam Physician 72(6):1037–1047PubMed Rindfleisch JA, Muller D (2005) Diagnosis and management of rheumatoid arthritis. Am Fam Physician 72(6):1037–1047PubMed
5.
go back to reference National Audit Office (2009) Services for people with rheumatoid arthritis. Report by the comptroller and auditor general, HC 823 session 2008–2009. National Audit Office, 15 July 2009 National Audit Office (2009) Services for people with rheumatoid arthritis. Report by the comptroller and auditor general, HC 823 session 2008–2009. National Audit Office, 15 July 2009
6.
go back to reference Andrianakos A, Trontzas P, Christoyannis F, Kaskani E, Nikolia Z, Tavaniotou E, Georgountzos A, Krachtis P, Group ES (2006) Prevalence and management of rheumatoid arthritis in the general population of Greece—the ESORDIG study. Rheumatology (Oxford) 45(12):1549–1554. doi:10.1093/rheumatology/kel140 CrossRef Andrianakos A, Trontzas P, Christoyannis F, Kaskani E, Nikolia Z, Tavaniotou E, Georgountzos A, Krachtis P, Group ES (2006) Prevalence and management of rheumatoid arthritis in the general population of Greece—the ESORDIG study. Rheumatology (Oxford) 45(12):1549–1554. doi:10.​1093/​rheumatology/​kel140 CrossRef
8.
go back to reference Smolen JS, Landewe R, Breedveld FC, Buch M, Burmester G, Dougados M, Emery P, Gaujoux-Viala C, Gossec L, Nam J, Ramiro S, Winthrop K, de Wit M, Aletaha D, Betteridge N, Bijlsma JW, Boers M, Buttgereit F, Combe B, Cutolo M, Damjanov N, Hazes JM, Kouloumas M, Kvien TK, Mariette X, Pavelka K, van Riel PL, Rubbert-Roth A, Scholte-Voshaar M, Scott DL, Sokka-Isler T, Wong JB, van der Heijde D (2013) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. doi:10.1136/annrheumdis-2013-204573 Smolen JS, Landewe R, Breedveld FC, Buch M, Burmester G, Dougados M, Emery P, Gaujoux-Viala C, Gossec L, Nam J, Ramiro S, Winthrop K, de Wit M, Aletaha D, Betteridge N, Bijlsma JW, Boers M, Buttgereit F, Combe B, Cutolo M, Damjanov N, Hazes JM, Kouloumas M, Kvien TK, Mariette X, Pavelka K, van Riel PL, Rubbert-Roth A, Scholte-Voshaar M, Scott DL, Sokka-Isler T, Wong JB, van der Heijde D (2013) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. doi:10.​1136/​annrheumdis-2013-204573
10.
go back to reference van den Hout WB, Goekoop-Ruiterman YP, Allaart CF, de Vries-Bouwstra JK, Hazes JM, Kerstens PJ, van Zeben D, Hulsmans HM, de Jonge-Bok JM, de Sonnaville PB, Dijkmans BA, Breedveld FC (2009) Cost-utility analysis of treatment strategies in patients with recent-onset rheumatoid arthritis. Arthritis Rheum 61(3):291–299. doi:10.1002/art.24169 CrossRefPubMed van den Hout WB, Goekoop-Ruiterman YP, Allaart CF, de Vries-Bouwstra JK, Hazes JM, Kerstens PJ, van Zeben D, Hulsmans HM, de Jonge-Bok JM, de Sonnaville PB, Dijkmans BA, Breedveld FC (2009) Cost-utility analysis of treatment strategies in patients with recent-onset rheumatoid arthritis. Arthritis Rheum 61(3):291–299. doi:10.​1002/​art.​24169 CrossRefPubMed
11.
go back to reference van der Velde G, Pham B, Machado M, Ieraci L, Witteman W, Bombardier C, Krahn M (2011) Cost-effectiveness of biologic response modifiers compared to disease-modifying antirheumatic drugs for rheumatoid arthritis: a systematic review. Arthritis Care Res (Hoboken) 63(1):65–78. doi:10.1002/acr.20338 CrossRef van der Velde G, Pham B, Machado M, Ieraci L, Witteman W, Bombardier C, Krahn M (2011) Cost-effectiveness of biologic response modifiers compared to disease-modifying antirheumatic drugs for rheumatoid arthritis: a systematic review. Arthritis Care Res (Hoboken) 63(1):65–78. doi:10.​1002/​acr.​20338 CrossRef
12.
go back to reference Keystone E, Heijde D, Mason D Jr, Landewe R, Vollenhoven RV, Combe B, Emery P, Strand V, Mease P, Desai C, Pavelka K (2008) Certolizumab pegol plus methotrexate is significantly more effective than placebo plus methotrexate in active rheumatoid arthritis: findings of a fifty-two-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum 58(11):3319–3329. doi:10.1002/art.23964 CrossRefPubMed Keystone E, Heijde D, Mason D Jr, Landewe R, Vollenhoven RV, Combe B, Emery P, Strand V, Mease P, Desai C, Pavelka K (2008) Certolizumab pegol plus methotrexate is significantly more effective than placebo plus methotrexate in active rheumatoid arthritis: findings of a fifty-two-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum 58(11):3319–3329. doi:10.​1002/​art.​23964 CrossRefPubMed
13.
go back to reference Smolen J, Landewe RB, Mease P, Brzezicki J, Mason D, Luijtens K, van Vollenhoven RF, Kavanaugh A, Schiff M, Burmester GR, Strand V, Vencovsky J, van der Heijde D (2009) Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomised controlled trial. Ann Rheum Dis 68(6):797–804. doi:10.1136/ard.2008.101659 CrossRefPubMed Smolen J, Landewe RB, Mease P, Brzezicki J, Mason D, Luijtens K, van Vollenhoven RF, Kavanaugh A, Schiff M, Burmester GR, Strand V, Vencovsky J, van der Heijde D (2009) Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomised controlled trial. Ann Rheum Dis 68(6):797–804. doi:10.​1136/​ard.​2008.​101659 CrossRefPubMed
14.
go back to reference Fleischmann R, Vencovsky J, van Vollenhoven RF, Borenstein D, Box J, Coteur G, Goel N, Brezinschek HP, Innes A, Strand V (2009) Efficacy and safety of certolizumab pegol monotherapy every 4 weeks in patients with rheumatoid arthritis failing previous disease-modifying antirheumatic therapy: the FAST4WARD study. Ann Rheum Dis 68(6):805–811. doi:10.1136/ard.2008.099291 CrossRefPubMed Fleischmann R, Vencovsky J, van Vollenhoven RF, Borenstein D, Box J, Coteur G, Goel N, Brezinschek HP, Innes A, Strand V (2009) Efficacy and safety of certolizumab pegol monotherapy every 4 weeks in patients with rheumatoid arthritis failing previous disease-modifying antirheumatic therapy: the FAST4WARD study. Ann Rheum Dis 68(6):805–811. doi:10.​1136/​ard.​2008.​099291 CrossRefPubMed
18.
go back to reference Launois R, Avouac B, Berenbaum F, Blin O, Bru I, Fautrel B, Joubert JM, Sibilia J, Combe B (2011) Comparison of certolizumab pegol with other anticytokine agents for treatment of rheumatoid arthritis: a multiple-treatment Bayesian metaanalysis. J Rheumatol 38(5):835–845. doi:10.3899/jrheum.100665 CrossRefPubMed Launois R, Avouac B, Berenbaum F, Blin O, Bru I, Fautrel B, Joubert JM, Sibilia J, Combe B (2011) Comparison of certolizumab pegol with other anticytokine agents for treatment of rheumatoid arthritis: a multiple-treatment Bayesian metaanalysis. J Rheumatol 38(5):835–845. doi:10.​3899/​jrheum.​100665 CrossRefPubMed
19.
go back to reference Bucher HC, Guyatt GH, Griffith LE, Walter SD (1997) The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 50(6):683–691CrossRefPubMed Bucher HC, Guyatt GH, Griffith LE, Walter SD (1997) The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 50(6):683–691CrossRefPubMed
20.
go back to reference Du Pan SM, Dehler S, Ciurea A, Ziswiler HR, Gabay C, Finckh A, Swiss Clinical Quality Management P (2009) Comparison of drug retention rates and causes of drug discontinuation between anti-tumor necrosis factor agents in rheumatoid arthritis. Arthritis Rheum 61(5):560–568. doi:10.1002/art.24463 CrossRefPubMed Du Pan SM, Dehler S, Ciurea A, Ziswiler HR, Gabay C, Finckh A, Swiss Clinical Quality Management P (2009) Comparison of drug retention rates and causes of drug discontinuation between anti-tumor necrosis factor agents in rheumatoid arthritis. Arthritis Rheum 61(5):560–568. doi:10.​1002/​art.​24463 CrossRefPubMed
21.
go back to reference Du Pan SM, Scherer A, Gabay C, Finckh A (2012) Differential drug retention between anti-TNF agents and alternative biological agents after inadequate response to an anti-TNF agent in rheumatoid arthritis patients. Ann Rheum Dis 71(6):997–999. doi:10.1136/annrheumdis-2011-200882 CrossRefPubMed Du Pan SM, Scherer A, Gabay C, Finckh A (2012) Differential drug retention between anti-TNF agents and alternative biological agents after inadequate response to an anti-TNF agent in rheumatoid arthritis patients. Ann Rheum Dis 71(6):997–999. doi:10.​1136/​annrheumdis-2011-200882 CrossRefPubMed
22.
go back to reference Edwards CJ, Arden NK, Fisher D, Saperia JC, Reading I, Van Staa TP, Cooper C (2005) The changing use of disease-modifying anti-rheumatic drugs in individuals with rheumatoid arthritis from the United Kingdom General Practice Research Database. Rheumatology (Oxford) 44(11):1394–1398. doi:10.1093/rheumatology/kei024 CrossRef Edwards CJ, Arden NK, Fisher D, Saperia JC, Reading I, Van Staa TP, Cooper C (2005) The changing use of disease-modifying anti-rheumatic drugs in individuals with rheumatoid arthritis from the United Kingdom General Practice Research Database. Rheumatology (Oxford) 44(11):1394–1398. doi:10.​1093/​rheumatology/​kei024 CrossRef
24.
go back to reference Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA, Spitz PW, Haga M, Kleinheksel SM, Cathey MA (1994) The mortality of rheumatoid arthritis. Arthritis Rheum 37(4):481–494CrossRefPubMed Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA, Spitz PW, Haga M, Kleinheksel SM, Cathey MA (1994) The mortality of rheumatoid arthritis. Arthritis Rheum 37(4):481–494CrossRefPubMed
25.
go back to reference Bansback N, Marra C, Tsuchiya A, Anis A, Guh D, Hammond T, Brazier J (2007) Using the health assessment questionnaire to estimate preference-based single indices in patients with rheumatoid arthritis. Arthritis Rheum 57(6):963–971. doi:10.1002/art.22885 CrossRefPubMed Bansback N, Marra C, Tsuchiya A, Anis A, Guh D, Hammond T, Brazier J (2007) Using the health assessment questionnaire to estimate preference-based single indices in patients with rheumatoid arthritis. Arthritis Rheum 57(6):963–971. doi:10.​1002/​art.​22885 CrossRefPubMed
26.
go back to reference Barton P, Jobanputra P, Wilson J, Bryan S, Burls A (2004) The use of modelling to evaluate new drugs for patients with a chronic condition: the case of antibodies against tumour necrosis factor in rheumatoid arthritis. Health Technol Assess 8(11):3 CrossRef Barton P, Jobanputra P, Wilson J, Bryan S, Burls A (2004) The use of modelling to evaluate new drugs for patients with a chronic condition: the case of antibodies against tumour necrosis factor in rheumatoid arthritis. Health Technol Assess 8(11):3 CrossRef
29.
go back to reference Chen YF, Jobanputra P, Barton P, Jowett S, Bryan S, Clark W, Fry-Smith A, Burls A (2006) 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 10(42):iii–iv–xi–xiii CrossRef Chen YF, Jobanputra P, Barton P, Jowett S, Bryan S, Clark W, Fry-Smith A, Burls A (2006) 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 10(42):iii–iv–xi–xiii CrossRef
32.
go back to reference Government Gazzette (2011) Ministerial Decision (FEK 2150B’/27-09-2011). Reimbursment from EOPYY for a day-case healthcare setting Government Gazzette (2011) Ministerial Decision (FEK 2150B’/27-09-2011). Reimbursment from EOPYY for a day-case healthcare setting
34.
go back to reference Government Gazzette. (2011) Ministerial Decision (FEK 262A’/16-12-2011). Reimbursment from EOPYY for a physician office visit Government Gazzette. (2011) Ministerial Decision (FEK 262A’/16-12-2011). Reimbursment from EOPYY for a physician office visit
35.
go back to reference Kobelt G, Jonsson L, Lindgren P, Young A, Eberhardt K (2002) Modeling the progression of rheumatoid arthritis: a two-country model to estimate costs and consequences of rheumatoid arthritis. Arthritis Rheum 46(9):2310–2319. doi:10.1002/art.10471 CrossRefPubMed Kobelt G, Jonsson L, Lindgren P, Young A, Eberhardt K (2002) Modeling the progression of rheumatoid arthritis: a two-country model to estimate costs and consequences of rheumatoid arthritis. Arthritis Rheum 46(9):2310–2319. doi:10.​1002/​art.​10471 CrossRefPubMed
38.
go back to reference Briggs AH (2000) Handling uncertainty in cost-effectiveness models. Pharmacoeconomics 17(5):479–500CrossRefPubMed Briggs AH (2000) Handling uncertainty in cost-effectiveness models. Pharmacoeconomics 17(5):479–500CrossRefPubMed
39.
go back to reference Briggs A, Claxton K, Sculpher M (2006) Decision modelling for health economic evaluation. Handbooks in health economic evaluation. Oxford University Press Inc, New York Briggs A, Claxton K, Sculpher M (2006) Decision modelling for health economic evaluation. Handbooks in health economic evaluation. Oxford University Press Inc, New York
43.
go back to reference Hyrich KL, Lunt M, Watson KD, Symmons DP, Silman AJ, British Society for Rheumatology Biologics R (2007) Outcomes after switching from one anti-tumor necrosis factor alpha agent to a second anti-tumor necrosis factor alpha agent in patients with rheumatoid arthritis: results from a large UK national cohort study. Arthritis Rheum 56(1):13–20. doi:10.1002/art.22331 CrossRefPubMed Hyrich KL, Lunt M, Watson KD, Symmons DP, Silman AJ, British Society for Rheumatology Biologics R (2007) Outcomes after switching from one anti-tumor necrosis factor alpha agent to a second anti-tumor necrosis factor alpha agent in patients with rheumatoid arthritis: results from a large UK national cohort study. Arthritis Rheum 56(1):13–20. doi:10.​1002/​art.​22331 CrossRefPubMed
44.
go back to reference Karlsson JA, Kristensen LE, Kapetanovic MC, Gulfe A, Saxne T, Geborek P (2008) Treatment response to a second or third TNF-inhibitor in RA: results from the South Swedish Arthritis Treatment Group Register. Rheumatology (Oxford) 47(4):507–513. doi:10.1093/rheumatology/ken034 CrossRef Karlsson JA, Kristensen LE, Kapetanovic MC, Gulfe A, Saxne T, Geborek P (2008) Treatment response to a second or third TNF-inhibitor in RA: results from the South Swedish Arthritis Treatment Group Register. Rheumatology (Oxford) 47(4):507–513. doi:10.​1093/​rheumatology/​ken034 CrossRef
45.
go back to reference Furst DE, Gaylis N, Bray V, Olech E, Yocum D, Ritter J, Weisman M, Wallace DJ, Crues J, Khanna D, Eckel G, Yeilding N, Callegari P, Visvanathan S, Rojas J, Hegedus R, George L, Mamun K, Gilmer K, Troum O (2007) Open-label, pilot protocol of patients with rheumatoid arthritis who switch to infliximab after an incomplete response to etanercept: the opposite study. Ann Rheum Dis 66(7):893–899. doi:10.1136/ard.2006.068304 CrossRefPubMedPubMedCentral Furst DE, Gaylis N, Bray V, Olech E, Yocum D, Ritter J, Weisman M, Wallace DJ, Crues J, Khanna D, Eckel G, Yeilding N, Callegari P, Visvanathan S, Rojas J, Hegedus R, George L, Mamun K, Gilmer K, Troum O (2007) Open-label, pilot protocol of patients with rheumatoid arthritis who switch to infliximab after an incomplete response to etanercept: the opposite study. Ann Rheum Dis 66(7):893–899. doi:10.​1136/​ard.​2006.​068304 CrossRefPubMedPubMedCentral
46.
go back to reference van Vollenhoven R, Harju A, Brannemark S, Klareskog L (2003) Treatment with infliximab (Remicade) when etanercept (Enbrel) has failed or vice versa: data from the STURE registry showing that switching tumour necrosis factor alpha blockers can make sense. Ann Rheum Dis 62(12):1195–1198CrossRefPubMedPubMedCentral van Vollenhoven R, Harju A, Brannemark S, Klareskog L (2003) Treatment with infliximab (Remicade) when etanercept (Enbrel) has failed or vice versa: data from the STURE registry showing that switching tumour necrosis factor alpha blockers can make sense. Ann Rheum Dis 62(12):1195–1198CrossRefPubMedPubMedCentral
Metadata
Title
Cost-utility analysis of certolizumab pegol in combination with methotrexate in patients with moderate-to-severe active rheumatoid arthritis in Greece
Authors
C. Tzanetakos
A. Tzioufas
A. Goules
G. Kourlaba
T. Theodoratou
P. Christou
N. Maniadakis
Publication date
01-09-2017
Publisher
Springer Berlin Heidelberg
Published in
Rheumatology International / Issue 9/2017
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-017-3736-z

Other articles of this Issue 9/2017

Rheumatology International 9/2017 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.