Abstract
Background: Societal decision makers increasingly emphasise their need for evidence based economic analyses to make reimbursement decisions.
Objective: To analyse the cost utility of adalimumab, on both incremental cost and incremental quality adjusted life years (QALYs), versus traditional disease modifying antirheumatic drugs and the other tumour necrosis factor (TNF) antagonists suitable for submission to the Swedish LFN (Pharmaceutical Benefit Board).
Methods: Swedish unit costs and treatment guidelines from a lifetime perspective were implemented. A mathematical model, incorporating data from seven trials, simulated the experiences of 10 000 hypothetical patients with moderate to severe rheumatoid arthritis (RA). The primary outcome measure—QALYs—was derived from utility values calculated from a relationship between the Health Assessment Questionnaire (HAQ) Disability Index (DI) and Health Utility Index-III (HUI-3) from adalimumab trial results. The model followed the progression of HAQ-DI through a number of treatments in a sequence accounting for mortality, drug and monitoring costs, and other direct costs.
Results: When using ACR50 as a response threshold for determining successful treatment, adalimumab plus methotrexate showed the greatest number of QALYs gained (2.3 from one study and 2.1 from the pooled results of two trials). The etanercept plus methotrexate strategy yielded QALY gains similar to the pooled adalimumab results. Except for the infliximab strategy, the costs results were between €35 000 and €42 000, a range normally considered cost effective in other European countries.
Conclusion: Adalimumab appears to be cost effective for the treatment of moderate to severe RA. The results suggest that adalimumab is at least as cost effective as other TNF antagonists.
Full Text
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Figure 1.
Diagrammatic display of a patient pathway.
Figure 2.
Incremental cost effectiveness results of all treatments v traditional DMARDs for ACR50/DAS28 good and ACR20/DAS28 moderate response rates.
Figure 3.
Cost effectiveness plane of adalimumab plus MTX6,8v DMARDs using an ACR50 threshold.
Figure 4.
Cost effectiveness acceptability curve of adalimumab plus MTX6,8v DMARDs and etanercept monotherapy12v DMARDs using an ACR50 threshold.
Figure 5.
Univariate sensitivity analysis.
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anderson J. J., Wells G., Verhoeven A. C., Felson D. T. Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration. Arthritis Rheum. 2000 Jan;43(1):22–29. doi: 10.1002/1529-0131(200001)43:1<22::AID-ANR4>3.0.CO;2-9. [DOI] [PubMed] [Google Scholar]
- Björnådal Lena, Baecklund Eva, Yin Li, Granath Fredrik, Klareskog Lars, Ekbom Anders. Decreasing mortality in patients with rheumatoid arthritis: results from a large population based cohort in Sweden, 1964-95. J Rheumatol. 2002 May;29(5):906–912. [PubMed] [Google Scholar]
- Breedveld F. C., Kalden J. R. Appropriate and effective management of rheumatoid arthritis. Ann Rheum Dis. 2004 Jun;63(6):627–633. doi: 10.1136/ard.2003.011395. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brennan A., Bansback N. Re: Wolfe et al. Do rheumatology cost-effectiveness analyses make sense? Rheumatology (Oxford) 2004 May;43(5):677–678. doi: 10.1093/rheumatology/keh096. [DOI] [PubMed] [Google Scholar]
- Brennan A., Bansback N., Reynolds A., Conway P. Modelling the cost-effectiveness of etanercept in adults with rheumatoid arthritis in the UK. Rheumatology (Oxford) 2003 Jul 30;43(1):62–72. doi: 10.1093/rheumatology/keg451. [DOI] [PubMed] [Google Scholar]
- Buxton M. J., Drummond M. F., Van Hout B. A., Prince R. L., Sheldon T. A., Szucs T., Vray M. Modelling in economic evaluation: an unavoidable fact of life. Health Econ. 1997 May-Jun;6(3):217–227. doi: 10.1002/(sici)1099-1050(199705)6:3<217::aid-hec267>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
- Choi H. K., Seeger J. D., Kuntz K. M. A cost-effectiveness analysis of treatment options for patients with methotrexate-resistant rheumatoid arthritis. Arthritis Rheum. 2000 Oct;43(10):2316–2327. doi: 10.1002/1529-0131(200010)43:10<2316::AID-ANR20>3.0.CO;2-6. [DOI] [PubMed] [Google Scholar]
- Conner-Spady Barbara, Suarez-Almazor Maria E. Variation in the estimation of quality-adjusted life-years by different preference-based instruments. Med Care. 2003 Jul;41(7):791–801. doi: 10.1097/00005650-200307000-00003. [DOI] [PubMed] [Google Scholar]
- Feeny David, Furlong William, Torrance George W., Goldsmith Charles H., Zhu Zenglong, DePauw Sonja, Denton Margaret, Boyle Michael. Multiattribute and single-attribute utility functions for the health utilities index mark 3 system. Med Care. 2002 Feb;40(2):113–128. doi: 10.1097/00005650-200202000-00006. [DOI] [PubMed] [Google Scholar]
- Felson D. T., Anderson J. J., Lange M. L., Wells G., LaValley M. P. Should improvement in rheumatoid arthritis clinical trials be defined as fifty percent or seventy percent improvement in core set measures, rather than twenty percent? Arthritis Rheum. 1998 Sep;41(9):1564–1570. doi: 10.1002/1529-0131(199809)41:9<1564::AID-ART6>3.0.CO;2-M. [DOI] [PubMed] [Google Scholar]
- Fries J. F. Reevaluating the therapeutic approach to rheumatoid arthritis: the "sawtooth" strategy. J Rheumatol Suppl. 1990 May;22:12–15. [PubMed] [Google Scholar]
- Furst Daniel E., Schiff Michael H., Fleischmann Roy M., Strand Vibeke, Birbara Charles A., Compagnone Daniele, Fischkoff Steven A., Chartash Elliot K. Adalimumab, a fully human anti tumor necrosis factor-alpha monoclonal antibody, and concomitant standard antirheumatic therapy for the treatment of rheumatoid arthritis: results of STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis). J Rheumatol. 2003 Dec;30(12):2563–2571. [PubMed] [Google Scholar]
- Geborek P., Crnkic M., Petersson I. F., Saxne T., South Swedish Arthritis Treatment Group Etanercept, infliximab, and leflunomide in established rheumatoid arthritis: clinical experience using a structured follow up programme in southern Sweden. Ann Rheum Dis. 2002 Sep;61(9):793–798. doi: 10.1136/ard.61.9.793. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hunink M. G., Bult J. R., de Vries J., Weinstein M. C. Uncertainty in decision models analyzing cost-effectiveness: the joint distribution of incremental costs and effectiveness evaluated with a nonparametric bootstrap method. Med Decis Making. 1998 Jul-Sep;18(3):337–346. doi: 10.1177/0272989X9801800312. [DOI] [PubMed] [Google Scholar]
- Jobanputra P., Barton P., Bryan S., Burls A. The effectiveness of infliximab and etanercept for the treatment of rheumatoid arthritis: a systematic review and economic evaluation. Health Technol Assess. 2002;6(21):1–110. doi: 10.3310/hta6210. [DOI] [PubMed] [Google Scholar]
- Keystone Edward C., Kavanaugh Arthur F., Sharp John T., Tannenbaum Hyman, Hua Ye, Teoh Leah S., Fischkoff Steven A., Chartash Elliot K. Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum. 2004 May;50(5):1400–1411. doi: 10.1002/art.20217. [DOI] [PubMed] [Google Scholar]
- Kobelt G., Eberhardt K., Jönsson L., Jönsson B. Economic consequences of the progression of rheumatoid arthritis in Sweden. Arthritis Rheum. 1999 Feb;42(2):347–356. doi: 10.1002/1529-0131(199902)42:2<347::AID-ANR18>3.0.CO;2-P. [DOI] [PubMed] [Google Scholar]
- Kobelt Gisela, Jönsson Linus, Lindgren Peter, Young Adam, Eberhardt Kerstin. Modeling the progression of rheumatoid arthritis: a two-country model to estimate costs and consequences of rheumatoid arthritis. Arthritis Rheum. 2002 Sep;46(9):2310–2319. doi: 10.1002/art.10471. [DOI] [PubMed] [Google Scholar]
- Lajas Cristina, Abasolo Lydia, Bellajdel Boutayeb, Hernández-García César, Carmona Loreto, Vargas Emilio, Lázaro Pablo, Jover Juan A. Costs and predictors of costs in rheumatoid arthritis: a prevalence-based study. Arthritis Rheum. 2003 Feb 15;49(1):64–70. doi: 10.1002/art.10905. [DOI] [PubMed] [Google Scholar]
- Leardini G., Salaffi F., Montanelli R., Gerzeli S., Canesi B. A multicenter cost-of-illness study on rheumatoid arthritis in Italy. Clin Exp Rheumatol. 2002 Jul-Aug;20(4):505–515. [PubMed] [Google Scholar]
- Maetzel Andreas, Tugwell Peter, Boers Maarten, Guillemin Francis, Coyle Doug, Drummond Mike, Wong John B., Gabriel Sherine E., OMERACT 6 Economics Research Group Economic evaluation of programs or interventions in the management of rheumatoid arthritis: defining a consensus-based reference case. J Rheumatol. 2003 Apr;30(4):891–896. [PubMed] [Google Scholar]
- Maini R., St Clair E. W., Breedveld F., Furst D., Kalden J., Weisman M., Smolen J., Emery P., Harriman G., Feldmann M. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet. 1999 Dec 4;354(9194):1932–1939. doi: 10.1016/s0140-6736(99)05246-0. [DOI] [PubMed] [Google Scholar]
- Moreland L. W., Schiff M. H., Baumgartner S. W., Tindall E. A., Fleischmann R. M., Bulpitt K. J., Weaver A. L., Keystone E. C., Furst D. E., Mease P. J. Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. Ann Intern Med. 1999 Mar 16;130(6):478–486. doi: 10.7326/0003-4819-130-6-199903160-00004. [DOI] [PubMed] [Google Scholar]
- Raftery J. NICE: faster access to modern treatments? Analysis of guidance on health technologies. BMJ. 2001 Dec 1;323(7324):1300–1303. doi: 10.1136/bmj.323.7324.1300. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sculpher M., Fenwick E., Claxton K. Assessing quality in decision analytic cost-effectiveness models. A suggested framework and example of application. Pharmacoeconomics. 2000 May;17(5):461–477. doi: 10.2165/00019053-200017050-00005. [DOI] [PubMed] [Google Scholar]
- Simonsson M., Bergman S., Jacobsson L. T., Petersson I. F., Svensson B. The prevalence of rheumatoid arthritis in Sweden. Scand J Rheumatol. 1999;28(6):340–343. doi: 10.1080/03009749950155319. [DOI] [PubMed] [Google Scholar]
- Smolen J. S., Sokka T., Pincus T., Breedveld F. C. A proposed treatment algorithm for rheumatoid arthritis: aggressive therapy, methotrexate, and quantitative measures. Clin Exp Rheumatol. 2003 Sep-Oct;21(5 Suppl 31):S209–S210. [PubMed] [Google Scholar]
- Song Fujian, Altman Douglas G., Glenny Anne-Marie, Deeks Jonathan J. Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. BMJ. 2003 Mar 1;326(7387):472–472. doi: 10.1136/bmj.326.7387.472. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stevenson M. D., Oakley J., Chilcott J. B. Gaussian process modeling in conjunction with individual patient simulation modeling: a case study describing the calculation of cost-effectiveness ratios for the treatment of established osteoporosis. Med Decis Making. 2004 Jan-Feb;24(1):89–100. doi: 10.1177/0272989X03261561. [DOI] [PubMed] [Google Scholar]
- Torrance G. W., Tugwell P., Amorosi S., Chartash E., Sengupta N. Improvement in health utility among patients with rheumatoid arthritis treated with adalimumab (a human anti-TNF monoclonal antibody) plus methotrexate. Rheumatology (Oxford) 2004 Mar 23;43(6):712–718. doi: 10.1093/rheumatology/keh153. [DOI] [PubMed] [Google Scholar]
- Weinblatt M. E., Kremer J. M., Bankhurst A. D., Bulpitt K. J., Fleischmann R. M., Fox R. I., Jackson C. G., Lange M., Burge D. J. A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med. 1999 Jan 28;340(4):253–259. doi: 10.1056/NEJM199901283400401. [DOI] [PubMed] [Google Scholar]
- Weinblatt Michael E., Keystone Edward C., Furst Daniel E., Moreland Larry W., Weisman Michael H., Birbara Charles A., Teoh Leah A., Fischkoff Steven A., Chartash Elliot K. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum. 2003 Jan;48(1):35–45. doi: 10.1002/art.10697. [DOI] [PubMed] [Google Scholar]
- Wolfe F. A reappraisal of HAQ disability in rheumatoid arthritis. Arthritis Rheum. 2000 Dec;43(12):2751–2761. doi: 10.1002/1529-0131(200012)43:12<2751::AID-ANR15>3.0.CO;2-6. [DOI] [PubMed] [Google Scholar]
- Wolfe F., Hawley D. J. The longterm outcomes of rheumatoid arthritis: Work disability: a prospective 18 year study of 823 patients. J Rheumatol. 1998 Nov;25(11):2108–2117. [PubMed] [Google Scholar]
- Wolfe F. The epidemiology of drug treatment failure in rheumatoid arthritis. Baillieres Clin Rheumatol. 1995 Nov;9(4):619–632. doi: 10.1016/s0950-3579(05)80305-x. [DOI] [PubMed] [Google Scholar]
- Wong John B., Singh Gurkirpal, Kavanaugh Arthur. Estimating the cost-effectiveness of 54 weeks of infliximab for rheumatoid arthritis. Am J Med. 2002 Oct 1;113(5):400–408. doi: 10.1016/s0002-9343(02)01243-3. [DOI] [PubMed] [Google Scholar]
- Yelin E., Wanke L. A. An assessment of the annual and long-term direct costs of rheumatoid arthritis: the impact of poor function and functional decline. Arthritis Rheum. 1999 Jun;42(6):1209–1218. doi: 10.1002/1529-0131(199906)42:6<1209::AID-ANR18>3.0.CO;2-M. [DOI] [PubMed] [Google Scholar]
- van de Putte L. B. A., Atkins C., Malaise M., Sany J., Russell A. S., van Riel P. L. C. M., Settas L., Bijlsma J. W., Todesco S., Dougados M. Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed. Ann Rheum Dis. 2004 May;63(5):508–516. doi: 10.1136/ard.2003.013052. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van de Putte L. B. A., Rau R., Breedveld F. C., Kalden J. R., Malaise M. G., van Riel P. L. C. M., Schattenkirchner M., Emery P., Burmester G. R., Zeidler H. Efficacy and safety of the fully human anti-tumour necrosis factor alpha monoclonal antibody adalimumab (D2E7) in DMARD refractory patients with rheumatoid arthritis: a 12 week, phase II study. Ann Rheum Dis. 2003 Dec;62(12):1168–1177. doi: 10.1136/ard.2003.009563. [DOI] [PMC free article] [PubMed] [Google Scholar]





