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Cost-utility analysis of de-escalating biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis


Autoři: Benjamin Birkner aff001;  Jürgen Rech aff002;  Tom Stargardt aff001
Působiště autorů: Hamburg Center for Health Economics (HCHE), Universität Hamburg, Hamburg, Germany aff001;  Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Department of Internal Medicine 3 – Rheumatology and Immunology, Universitätsklinikum Erlangen, Erlangen, Germany aff002
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0226754

Souhrn

Objective

Recent guideline updates have suggested de-escalating DMARDs when patients with rheumatoid arthritis achieve remission or low disease activity. We aim to evaluate whether it is cost-effective to de-escalate the biological form of DMARDs (bDMARDs).

Methods

Using a Markov model, we performed a cost-utility analysis for RA patients on bDMARD treatment. We compared continuing treatment (standard care) to a tapering approach (i.e., an immediate 50% dose reduction), withdrawal (i.e., an immediate 100% dose reduction) and tapering followed by withdrawal of bDMARDs. The parametrization is based on a comprehensive literature review. Results were computed for 30 years with a cycle length of three months. We applied the payer’s perspective for Germany and conducted deterministic and probabilistic sensitivity analyses.

Results

Tapering or withdrawing bDMARD treatment resulted in ICERs of €526,254 (incr. costs -78,845, incr. QALYs -0.1498) or €216,879 (incr. costs -€121,691, incr. QALYs -0.5611) compared to standard care. Tapering followed by withdrawal resulted in a loss of 0.4354 QALYs and savings of €107,969 per patient, with an ICER of €247,987. Deterministic sensitivity analysis revealed that our results remained largely unaffected by parameter changes. Probabilistic sensitivity analysis suggests that tapering, withdrawal and tapering followed by withdrawal were dominant in 39.8%, 28.2% and 29.0% of 10,000 iterations.

Conclusion

Our findings suggest that de-escalating bDMARDs in patients with RA may result in high cost savings but also a decrease in quality of life compared to standard care. If decision makers choose to implement de-escalation in daily practice, our results suggest the tapering approach.

Klíčová slova:

Markov models – Rheumatoid arthritis – Drug therapy – Quality of life – Germany – NSAIDs – Randomized controlled trials


Zdroje

1. Alamanos Y, Voulgari PV, Drosos AA. Incidence and Prevalence of Rheumatoid Arthritis, Based on the 1987 American College of Rheumatology Criteria: A Systematic Review. Semin Arthritis Rheum. 2006;36: 182–188. doi: 10.1016/j.semarthrit.2006.08.006 17045630

2. Hense S, Ramos AL, Callhoff J, Albrecht K, Zink A, Hoffmann F. Prävalenz der rheumatoiden Arthritis in Deutschland auf Basis von Kassendaten. Z Für Rheumatol. 2016;75: 819–827.

3. Smolen JS, Landewé R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017; 1–18. doi: 10.1136/annrheumdis-2016-210715 28264816

4. Jönsson B, Kobelt G, Smolen J. The burden of rheumatoid arthritis and access to treatment: uptake of new therapies. Eur J Health Econ. 2008;8: 61–86. doi: 10.1007/s10198-007-0089-7 18097697

5. Huscher D, Mittendorf T, von Hinüber U, Kötter I, Hoese G, Pfäfflin A, et al. Evolution of cost structures in rheumatoid arthritis over the past decade. Ann Rheum Dis. 2015;74: 738–745. doi: 10.1136/annrheumdis-2013-204311 24406543

6. Albrecht K, Huscher D, Eidner T, Kleinert S, Späthling-Mestekemper S, Bischoff S, et al. Versorgung der rheumatoiden Arthritis 2014. Z Für Rheumatol. 2017;76: 50–57. doi: 10.1007/s00393-016-0156-5

7. Böger RH, Schmidt G. Antirheumatika und Antiphlogistika. In: Schwabe U, Paffrath D, editors. Arzneiverordnungs-Report 2016. Springer Berlin Heidelberg; 2016. pp. 369–380. doi: 10.1007/978-3-662-50351-5_19

8. Fiehn C, Holle J, Iking-Konert C, Leipe J, Weseloh C, Frerix M, et al. S2e-Leitlinie: Therapie der rheumatoiden Arthritis mit krankheitsmodifizierenden Medikamenten. Z Für Rheumatol. 2018; 1–19. doi: 10.1007/s00393-018-0481-y

9. Singh JA, Saag KG, Bridges SL, Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016;68: 1–26. doi: 10.1002/art.39480 26545940

10. Lau CS, Chia F, Harrison A, Hsieh T-Y, Jain R, Jung SM, et al. APLAR rheumatoid arthritis treatment recommendations. Int J Rheum Dis. 2015;18: 685–713. doi: 10.1111/1756-185X.12754 26334449

11. Schett G, Emery P, Tanaka Y, Burmester G, Pisetsky DS, Naredo E, et al. Tapering biologic and conventional DMARD therapy in rheumatoid arthritis: current evidence and future directions. Ann Rheum Dis. 2016;75: 1428–1437. doi: 10.1136/annrheumdis-2016-209201 27261493

12. Nam JL, Ramiro S, Gaujoux-Viala C, Takase K, Leon-Garcia M, Emery P, et al. Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2014;73: 516–528. doi: 10.1136/annrheumdis-2013-204577 24399231

13. Kuijper T, Lamers-Karnebeek F, Jacobs J, Hazes J, Luime J. Flare Rate in Patients with Rheumatoid Arthritis in Low Disease Activity or Remission When Tapering or Stopping Synthetic or Biologic DMARD: A Systematic Review. J Rheumatol. 2015; 2012–22. doi: 10.3899/jrheum.141520 26428204

14. Vanier A, Mariette X, Tubach F, Fautrel B. Cost-Effectiveness of TNF-Blocker Injection Spacing for Patients with Established Rheumatoid Arthritis in Remission: An Economic Evaluation from the Spacing of TNF-Blocker Injections in Rheumatoid Arthritis Trial. Value Health. 2017;20: 577–585. doi: 10.1016/j.jval.2017.01.005 28407999

15. Tran‐Duy A, Moghadam MG, Voshaar MAHO, Vonkeman HE, Boonen A, Clarke P, et al. An Economic Evaluation of Stopping Versus Continuing Tumor Necrosis Factor Inhibitor Treatment in Rheumatoid Arthritis Patients With Disease Remission or Low Disease Activity. Arthritis Rheumatol. 2018;70: 1557–1564. doi: 10.1002/art.40546 29745059

16. Kobelt G. Treating to Target with Etanercept in Rheumatoid Arthritis: Cost-Effectiveness of Dose Reductions When Remission Is Achieved. Value Health. 2014;17: 537–544. doi: 10.1016/j.jval.2014.04.005 25128046

17. Filipović-Pierucci A, Zarca K, Durand-Zaleski I. Markov Models for Health Economic Evaluations: The R Package heemod. ArXiv170203252 Stat. 2017 [cited 12 Oct 2017]. http://arxiv.org/abs/1702.03252

18. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7: 177–188. doi: 10.1016/0197-2456(86)90046-2 3802833

19. Emery P, Hammoudeh M, FitzGerald O, Combe B, Martin-Mola E, Buch MH, et al. Sustained Remission with Etanercept Tapering in Early Rheumatoid Arthritis. N Engl J Med. 2014;371: 1781–1792. doi: 10.1056/NEJMoa1316133 25372086

20. Tanaka Y, Hirata S, Kubo S, Fukuyo S, Hanami K, Sawamukai N, et al. Discontinuation of adalimumab after achieving remission in patients with established rheumatoid arthritis: 1-year outcome of the HONOR study. Ann Rheum Dis. 2015;74: 389–395. doi: 10.1136/annrheumdis-2013-204016 24288014

21. Haschka J, Englbrecht M, Hueber AJ, Manger B, Kleyer A, Reiser M, et al. Relapse rates in patients with rheumatoid arthritis in stable remission tapering or stopping antirheumatic therapy: interim results from the prospective randomised controlled RETRO study. Ann Rheum Dis. 2016;75: 45–51. doi: 10.1136/annrheumdis-2014-206439 25660991

22. Smolen JS, Nash P, Durez P, Hall S, Ilivanova E, Irazoque-Palazuelos F, et al. Maintenance, reduction, or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis (PRESERVE): a randomised controlled trial. The Lancet. 2013;381: 918–929. doi: 10.1016/S0140-6736(12)61811-X

23. Smolen JS, Emery P, Fleischmann R, van Vollenhoven RF, Pavelka K, Durez P, et al. Adjustment of therapy in rheumatoid arthritis on the basis of achievement of stable low disease activity with adalimumab plus methotrexate or methotrexate alone: the randomised controlled OPTIMA trial. The Lancet. 2014;383: 321–332. doi: 10.1016/S0140-6736(13)61751-1

24. van Herwaarden N, van der Maas A, Minten MJM, van den Hoogen FHJ, Kievit W, van Vollenhoven RF, et al. Disease activity guided dose reduction and withdrawal of adalimumab or etanercept compared with usual care in rheumatoid arthritis: open label, randomised controlled, non-inferiority trial. BMJ. 2015;350: h1389. doi: 10.1136/bmj.h1389 25858265

25. Keystone EC, Pope JE, Thorne JC, Poulin-Costello M, Phan-Chronis K, Vieira A, et al. Two-year radiographic and clinical outcomes from the Canadian Methotrexate and Etanercept Outcome study in patients with rheumatoid arthritis. Rheumatol Oxf Engl. 2016;55: 327–334. doi: 10.1093/rheumatology/kev338 26361879

26. Westhovens R, Yocum D, Han J, Berman A, Strusberg I, Geusens P, et al. The safety of infliximab, combined with background treatments, among patients with rheumatoid arthritis and various comorbidities: A large, randomized, placebo-controlled trial. Arthritis Rheum. 2006;54: 1075–1086. doi: 10.1002/art.21734 16572442

27. Emery P, Breedveld FC, Hall S, Durez P, Chang DJ, Robertson D, et al. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. The Lancet. 2008;372: 375–382. doi: 10.1016/S0140-6736(08)61000-4

28. Schiff M, Keiserman M, Codding C, Songcharoen S, Berman A, Nayiager S, et al. Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Ann Rheum Dis. 2008;67: 1096–1103. doi: 10.1136/ard.2007.080002 18055472

29. Kavanaugh A, Fleischmann RM, Emery P, Kupper H, Redden L, Guerette B, et al. Clinical, functional and radiographic consequences of achieving stable low disease activity and remission with adalimumab plus methotrexate or methotrexate alone in early rheumatoid arthritis: 26-week results from the randomised, controlled OPTIMA study. Ann Rheum Dis. 2013;72: 64–71. doi: 10.1136/annrheumdis-2011-201247 22562973

30. Dougados M, Kissel K, Conaghan PG, Mola EM, Schett G, Gerli R, et al. Clinical, radiographic and immunogenic effects after 1 year of tocilizumab-based treatment strategies in rheumatoid arthritis: the ACT-RAY study. Ann Rheum Dis. 2014;73: 803–809. doi: 10.1136/annrheumdis-2013-204761 24473673

31. Nam JL, Villeneuve E, Hensor EMA, Wakefield RJ, Conaghan PG, Green MJ, et al. A randomised controlled trial of etanercept and methotrexate to induce remission in early inflammatory arthritis: the EMPIRE trial. Ann Rheum Dis. 2014;73: 1027–1036. doi: 10.1136/annrheumdis-2013-204882 24618266

32. Tanaka Y, Takeuchi T, Mimori T, Saito K, Nawata M, Kameda H, et al. Discontinuation of infliximab after attaining low disease activity in patients with rheumatoid arthritis: RRR (remission induction by Remicade in RA) study. Ann Rheum Dis. 2010;69: 1286–1291. doi: 10.1136/ard.2009.121491 20360136

33. Wiens A, Venson R, Correr CJ, Otuki MF, Pontarolo R. Meta-analysis of the Efficacy and Safety of Adalimumab, Etanercept, and Infliximab for the Treatment of Rheumatoid Arthritis. Pharmacother J Hum Pharmacol Drug Ther. 2010;30: 339–353. doi: 10.1592/phco.30.4.339 20334454

34. Kremer JM, Dougados M, Emery P, Durez P, Sibilia J, Shergy W, et al. Treatment of rheumatoid arthritis with the selective costimulation modulator abatacept: Twelve‐month results of a phase iib, double‐blind, randomized, placebo‐controlled trial. Arthritis Amp Rheumatol. 2005;52: 2263–2271. doi: 10.1002/art.21201 16052582

35. Rubbert-Roth A, Tak PP, Zerbini C, Tremblay J-L, Carreño L, Armstrong G, et al. Efficacy and safety of various repeat treatment dosing regimens of rituximab in patients with active rheumatoid arthritis: results of a Phase III randomized study (MIRROR). Rheumatology. 2010;49: 1683–1693. doi: 10.1093/rheumatology/keq116 20463186

36. Kim H-Y, Hsu P-N, Barba M, Sulaiman W, Robertson D, Vlahos B, et al. Randomized comparison of etanercept with usual therapy in an Asian population with active rheumatoid arthritis: the APPEAL trial. Int J Rheum Dis. 2012;15: 188–196. doi: 10.1111/j.1756-185X.2011.01680.x 22462423

37. Yoo DH, Hrycaj P, Miranda P, Ramiterre E, Piotrowski M, Shevchuk S, et al. A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Ann Rheum Dis. 2013;72: 1613–1620. doi: 10.1136/annrheumdis-2012-203090 23687260

38. Hørslev-Petersen K, Hetland ML, Junker P, Pødenphant J, Ellingsen T, Ahlquist P, et al. Adalimumab added to a treat-to-target strategy with methotrexate and intra-articular triamcinolone in early rheumatoid arthritis increased remission rates, function and quality of life. The OPERA Study: an investigator-initiated, randomised, double-blind, parallel-group, placebo-controlled trial. Ann Rheum Dis. 2014;73: 654–661. doi: 10.1136/annrheumdis-2012-202735 23434570

39. Machado DA, Guzman RM, Xavier RM, Simon JA, Mele L, Pedersen R, et al. Open-Label Observation of Addition of Etanercept Versus a Conventional Disease-Modifying Antirheumatic Drug in Subjects With Active Rheumatoid Arthritis Despite Methotrexate Therapy in the Latin American Region. JCR J Clin Rheumatol. 2014;20: 25–33. doi: 10.1097/RHU.0000000000000055 24356474

40. Schiff M, Weinblatt ME, Valente R, van der Heijde D, Citera G, Elegbe A, et al. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: two-year efficacy and safety findings from AMPLE trial. Ann Rheum Dis. 2014;73: 86–94. doi: 10.1136/annrheumdis-2013-203843 23962455

41. Briggs A, Claxton K, Sculpher M. Decision modelling for health economic evaluation. Reprint. Oxford [u.a.]: Oxford Univ. Press; 2011.

42. Listing J, Kekow J, Manger B, Burmester G-R, Pattloch D, Zink A, et al. Mortality in rheumatoid arthritis: the impact of disease activity, treatment with glucocorticoids, TNFα inhibitors and rituximab. Ann Rheum Dis. 2013; 514–21. doi: 10.1136/annrheumdis-2013-204021 24291654

43. Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. The Lancet. 2016;388: 2023–2038. doi: 10.1016/S0140-6736(16)30173-8

44. Welsing PMJ, Severens JL, Hartman M, van Gestel AM, van Riel PLCM, Laan RFJM. The Initial Validation of a Markov Model for the Economic Evaluation of (New) Treatments for Rheumatoid Arthritis. PharmacoEconomics. 2006;24: 1011–1020. doi: 10.2165/00019053-200624100-00008 17002483

45. Fautrel B, Cukierman G, Joubert J-M, Laurendeau C, Gourmelen J, Fagnani F. Healthcare service utilisation costs attributable to rheumatoid arthritis in France: Analysis of a representative national claims database. Joint Bone Spine. 2016;83: 53–56. doi: 10.1016/j.jbspin.2015.02.023 26671705

46. Lundkvist J, Kastäng F, Kobelt G. The burden of rheumatoid arthritis and access to treatment: health burden and costs. Eur J Health Econ. 2008;8: 49–60. doi: 10.1007/s10198-007-0088-8 18157732

47. Dakin H, Burns R, Yang Y. HERC database of mapping studies, Version 5.0 (Last updated: 16th May 2016). 2016. http://www.herc.ox.ac.uk/downloads/herc-database-of-mapping-studies

48. Ara R, Brazier J. Deriving an Algorithm to Convert the Eight Mean SF-36 Dimension Scores into a Mean EQ-5D Preference-Based Score from Published Studies (Where Patient Level Data Are Not Available). Value Health. 2008;11: 1131–1143. doi: 10.1111/j.1524-4733.2008.00352.x 18489495

49. Neubauer S, Cifaldi M, Mittendorf T, Ganguli A, Wolff M, Zeidler J. Biologic TNF inhibiting agents for treatment of rheumatoid arthritis: persistence and dosing patterns in Germany. Health Econ Rev. 2014;4: 32. doi: 10.1186/s13561-014-0032-4 26208932

50. Hutubessy R, Chisholm D, Edejer TT-T, WHO-CHOICE. Generalized cost-effectiveness analysis for national-level priority-setting in the health sector. Cost Eff Resour Alloc. 2003;1: 8. doi: 10.1186/1478-7547-1-8 14687420

51. Ahlert M, Breyer F, Schwettmann L. How you ask is what you get: Framing effects in willingness-to-pay for a QALY. Soc Sci Med. 2016;150: 40–48. doi: 10.1016/j.socscimed.2015.11.055 26730880

52. O’Brien BJ, Goeree R, Gafni A, Torrance GW, Pauly MV, Erder H, et al. Assessing the Value of a New Pharmaceutical: A Feasibility Study of Contingent Valuation in Managed Care. Med Care. 1998;36: 370–384. doi: 10.1097/00005650-199803000-00013 9520961

53. Carthy T, Chilton S, Covey J, Hopkins L, Jones-Lee M, Loomes G, et al. On the Contingent Valuation of Safety and the Safety of Contingent Valuation: Part 2—The CV/SG "Chained" Approach. J Risk Uncertain. 1998;17: 187–214. doi: 10.1023/A:1007782800868

54. Markusse IM, Akdemir G, Huizinga TWJ, Allaart CF. Drug-free holiday in patients with rheumatoid arthritis: a qualitative study to explore patients’ opinion. Clin Rheumatol. 2014;33: 1155–1159. doi: 10.1007/s10067-014-2500-y 24469272

55. Aletaha D, Smolen J. The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI): a review of their usefulness and validity in rheumatoid arthritis. Clin Exp Rheumatol. 2005;23: S100–8. 16273793


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