Cost per responder for upadacitinib vs abatacept in patients with moderate-to-severe Rheumatoid Arthritis in Italy
Keywords:Abatacept, Cost per responder, Italian NHS, Rheumatoid Arthritis, Upadacitinib
Purpose: The objective of this economic evaluation was to compare the cost per responder between upadacitinib and abatacept (intravenous [iv] or subcutaneous [sc]) in patients with moderate-to-severe Rheumatoid Arthritis (RA) in Italy.
Methods: The clinical efficacy was assessed based on SELECT-CHOICE study results. The clinical efficacy of upadacitinib and abatacept (iv or sc) was measured by Clinical Remission (CR), Low Disease Activity (LDA) and American College of Rheumatology response (ACR20, 50 and 70). The treatment cost was based on the number of administrations dispensed at 12 or 24 weeks. The cost per responder was adopted as a cost-effectiveness indicator.
Results: Independent of the clinical efficacy measure used and the duration of treatment considered, the cost per responder was consistently lower for upadacitinib compared to abatacept (iv or sc) across all clinical measures. For example, considering the CR at 24 weeks, the cost per responder for upadacitinib was € 9,417 compared to € 17,817 for abatacept sc or to € 23,110 for abatacept iv. The differences in the cost per responder between upadacitinib and abatacept (iv or sc) increased when higher ACR response levels were considered.
Conclusions: These results suggested that upadacitinib is a cost-effectiveness option compared to abatacept (iv or sc) from the perspective of the Italian National Health Service in patients with moderate-to-severe Rheumatoid Arthritis in Italy.
Gibofsky A. Epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis: A Synopsis. Am J Manag Care. 2014;20(7)(suppl):S128-S135. PMID:25180621
Gibofsky A. Overview of epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis. Am J Manag Care. 2012;18(13)(suppl):S295-S302. PMID:23327517
World Health Organization. Chronic diseases and health promotion. Chronic rheumatic conditions. (Accessed March 2021) http://www.who.int/chp/topics/rheumatic/en/
Salaffi F, De Angelis R, Grassi W; MArche Pain Prevalence; INvestigation Group (MAPPING) study. Prevalence of musculoskeletal conditions in an Italian population sample: results of a regional community-based study. I. The MAPPING study. Clin Exp Rheumatol. 2005;23(6):819-828. PMID:16396700
Rossini M, Rossi E, Bernardi D, et al. Prevalence and incidence of rheumatoid arthritis in Italy. Rheumatol Int. 2014;34(5):659-664. https://doi.org/10.1007/s00296-014-2974-6 PMID:24610538
Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020;79(6):685-699. https://doi.org/10.1136/annrheumdis-2019-216655PMID:31969328
Nell VP, Machold KP, Eberl G, Stamm TA, Uffmann M, Smolen JS. Benefit of very early referral and very early therapy with disease-modifying anti-rheumatic drugs in patients with early rheumatoid arthritis. Rheumatology (Oxford). 2004;43(7):906-914. https://doi.org/10.1093/rheumatology/keh199 PMID:15113999
Emery P, Breedveld FC, Dougados M, Kalden JR, Schiff MH, Smolen JS. Early referral recommendation for newly diagnosed rheumatoid arthritis: evidence based development of a clinical guide. Ann Rheum Dis. 2002;61(4):290-297. https://doi.org/10.1136/ard.61.4.290PMID:11874828
Kuek A, Hazleman BL, Ostör AJK. Immune-mediated inflammatory diseases (IMIDs) and biologic therapy: a medical revolution. Postgrad Med J. 2007;83(978):251-260. https://doi.org/10.1136/pgmj.2006.052688 PMID:17403952
Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet. 2001;358:903-911. https://doi.org/10.1016/S0140-6736(01)06075-5 PMID:11567728
Caporali R, Conti F, Alivernini S, et al; Italian Society for Rheumatology. Recommendations for the use of biologic therapy in rheumatoid arthritis: update from the Italian Society for Rheumatology I. Efficacy. Clin Exp Rheumatol. 2011;29(3)(suppl 66):S7-S14. PMID:21906423
Strand V, Kremer JM, Gruben D, Krishnaswami S, Zwillich SH, Wallenstein GV. Tofacitinib in Combination With Conventional Disease-Modifying Antirheumatic Drugs in Patients With Active Rheumatoid Arthritis: Patient-Reported Outcomes From a Phase III Randomized Controlled Trial. Arthritis Care Res (Hoboken). 2017;69(4):592-598. https://doi.org/10.1002/acr.23004 PMID:27565000
van Vollenhoven RF, Fleischmann R, Cohen S, et al; ORAL Standard Investigators. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med. 2012;367(6):508-519. https://doi.org/10.1056/NEJMoa1112072 PMID:22873531
Fleischmann R, Schiff M, van der Heijde D, et al. Baricitinib, Methotrexate, or Combination in Patients With Rheumatoid Arthritis and No or Limited Prior Disease-Modifying Antirheumatic Drug Treatment. Arthritis Rheumatol. 2017;69(3):506-517. https://doi.org/10.1002/art.39953PMID:27723271
Taylor PC, Keystone EC, van der Heijde D, et al. Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2017;376(7):652-662. https://doi.org/10.1056/NEJMoa1608345 PMID:28199814
Thwaites C, Finney A. Rheumatoid arthritis. 2: exploring treatment options to achieve early control and remission. Nurs Times. 2010;106(10):18-20. PMID:20426296
National Institute for Health and Clinical Excellence. Rheumatoid arthritis (CG79): full guideline. London, UK: NICE; 2009. Online http://guidance.nice.org.uk/CG79/Guidance
van der Heijde DMFM, van ’t Hof M, van Riel PLCM, van de Putte LBA. Development of a disease activity score based on judgment in clinical practice by rheumatologists. J Rheumatol. 1993;20(3):579-581. PMID:8478878
van Gestel AM, Prevoo ML, van ’t Hof MA, van Rijswijk MH, van de Putte LB, van Riel PL. Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis. Comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism Criteria. Arthritis Rheum. 1996;39(1):34-40. https://doi.org/10.1002/art.1780390105 PMID:8546736
Prevoo ML, van ’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995;38(1):44-48. https://doi.org/10.1002/art.1780380107 PMID:7818570
van Gestel AM, Haagsma CJ, van Riel PL. Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum. 1998 Oct;41(10):1845-50. https://doi.org/10.1002/1529-0131(199810)41:10<1845::AID-ART17>3.0.CO;2-K PMID: 9778226.
Salaffi F, Cimmino MA, Leardini G, Gasparini S, Grassi W. Disease activity assessment of rheumatoid arthritis in daily practice: validity, internal consistency, reliability and congruency of the Disease Activity Score including 28 joints (DAS28) compared with the Clinical Disease Activity Index (CDAI). Clin Exp Rheumatol. 2009;27(4):552-559. PMID:19772784
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(5)(suppl 39):S100-S108. PMID:16273793
Upadacitinib RCP. (Accessed November 2020) https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_it.pdf
Burmester GR, Kremer JM, Van den Bosch F, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391(10139):2503-2512. https://doi.org/10.1016/S0140-6736(18)31115-2 PMID:29908669
Fleischmann R, Pangan AL, Song IH, et al. Upadacitinib versus placebo or adalimumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III, double-blind, randomized controlled trial. Arthritis Rheumatol. 2019;71(11):1788-1800. https://doi.org/10.1002/art.41032 PMID:31287230
Genovese MC, Fleischmann R, Combe B, et al. Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomised controlled phase 3 trial. Lancet. 2018;391(10139):2513-2524. https://doi.org/10.1016/S0140-6736(18)31116-4 PMID:29908670
Smolen JS, Pangan AL, Emery P, et al. Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): a randomised, placebo-controlled, double-blind phase 3 study. Lancet. 2019;393(10188):2303-2311. https://doi.org/10.1016/S0140-6736(19)30419-2 PMID:31130260
van Vollenhoven R, Takeuchi T, Pangan AL, et al. Efficacy and safety of upadacitinib monotherapy in methotrexatenaïve patients with moderately to severely active rheumatoid arthritis (SELECT-EARLY): a randomized, double-blind, active-comparator, multi-center, multi-country trial. Arthritis Rheumatol. 2020; Epub ahead of print.
Rubbert-Roth A, Enejosa J, Pangan AL, et al. Trial of Upadacitinib or Abatacept in Rheumatoid Arthritis. N Engl J Med. 2020;383(16):1511-1521. https://doi.org/10.1056/NEJMoa2008250 PMID:33053283
Rubbert-Roth A, Enejosa J, Pangan AL et al. Efficacy and safety of upadacitinib vs abatacept in patients with active rheumatoid arthritis and prior inadequate response or intolerance to biologic disease-modifying anti-rheumaticdDrugs (SELECT-CHOICE): A double-blind, randomized controlled phase 3 trial. Presented at the European Congress of Rheumatology, 3–6 June 2020. https://ard.bmj.com/content/79/Suppl_1/1015
Abatacept RCP. (Accessed November 2020) https://www.ema.europa.eu/en/documents/product-information/orencia-epar-product-information_it.pdf
Genovese MC, Covarrubias A, Leon G, et al. Subcutaneous abatacept versus intravenous abatacept: a phase IIIb noninferiority study in patients with an inadequate response to methotrexate. Arthritis Rheum. 2011 (10):2854-64. https//doi.org/10.1002/art.30463 . PMID: 21618201
Fattore G. Gruppo di lavoro AIES (coordinato da G. Fattore). Proposta di linee guida per la valutazione economica degli interventi sanitari in Italia. PharmacoEcon Ital Res Artic. 2009;11(2):83-93. https://doi.org/10.1007/BF03320660
National Institute for Health and Care Excellence. Guide to the methods of technology appraisal. 2013. (Accessed March 2021) http://www.nice.org.uk/aboutnice/howwework/devnicetech/guidetothemethodsoftechnologyappraisal.jsp.
Canadian Agency for Drugs and Technologies in Health. Guidelines for the Economic Evaluation of Health Technologies: Canada, 3rd Edition. 2006. (Accessed March 2021). https://www.cadth.ca/about-cadth/how-we-do-it/methods-and-guidelines/guidelines-for-the-economic-evaluation-of-health-technologies-canada
NICE Guidance. Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for rheumatoid arthritis not previously treated with DMARDs or after conventional DMARDs only have failed. Technology appraisal guidance Published: 26 January 2016. (Accessed March 2021) https://www.nice.org.uk/guidance/ta375/resources/adalimumab-etanercept-infliximab-certolizumab-pegol-golimumab-tocilizumab-and-abatacept-for-rheumatoid-arthritis-not-previously-treated-with-dmards-or-after-conventional-dmards-only-have-failed-pdf-82602790920133.
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