https://doi.org/10.4081/reumatismo.2023.1602
Anti-tumor necrosis factor α: originators versus biosimilars, comparison in clinical response assessment in a multicenter cohort of patients with inflammatory arthropathies
Submitted: 16 June 2023
Accepted: 25 September 2023
Published: 19 December 2023
Accepted: 25 September 2023
Abstract Views: 1589
PDF: 365
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Objective. To compare etanercept and adalimumab biosimilars (SB4 and ABP501) and respective bioriginators in terms of safety and efficacy in a real-life contest.
Methods. We consequently enrolled patients affected by rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, treated with SB4, and ABP501, or with corresponding originators, belonging to the main biological prescribing centers in the Lazio region (Italy), from 2017 to 2020. Data were collected at recruitment and after 4, 8, 12, and 24 months of therapy.
Results. The multicenter cohort was composed by 455 patients treated with biosimilars [SB4/ABP501 276/179; female/male 307/146; biologic disease-modifying anti-rheumatic drug (b-DMARD) naïve 56%, median age/ interquartile range 55/46-65 years] and 436 treated with originators (etanercept/adalimumab 186/259, female/ male 279/157, b-DMARD naïve 67,2%, median age/interquartile range 53/43-62 years). No differences were found about safety, but the biosimilar group presented more discontinuations due to inefficacy (p<0.001). Female gender, being a smoker, and being b-DMARD naïve were predictive factors of reduced drug survival (p=0.05, p=0.046, p=0.001 respectively). The retention rate at 24 months was 81.1% for bioriginators and 76.5% for biosimilars (median retention time of 20.7 and 18.9 months, respectively) (p=0.002). Patients with remission/low disease activity achievement at 4 months showed a cumulative survival of 90% to biosimilar therapy until 24 months (p=0.001); early adverse reactions instead represented a cause of subsequent drug discontinuation (p=0.001).
Conclusions. Real-life data demonstrated a similar safety profile between biosimilars and originators, but a reduced biosimilar retention rate at 24 months. Biosimilars could be considered a valid, safe, and less expensive alternative to originators, allowing access to treatments for a wider patient population.
Elliot MJ, Maini RN, Feldmann M, Kalden JR, Antoni C, Smolen JS, et al. Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet 1994; 344: 1105-10.
DOI: https://doi.org/10.1016/S0140-6736(94)90628-9
Sfikakis PP. The first decade of biologic TNF antagonists in clinical practice: lessons learned, unresolved issues and future directions. Curr Dir Autoimmun 2010; 11: 180-210.
DOI: https://doi.org/10.1159/000289205
Keystone EC, Schiff MH, Kremer JM, Kafka S, Lovy M, DeVries T, et al. Once-weekly administration of 50 mg etanercept in patients with active rheumatoid arthritis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2004; 50: 353-63.
DOI: https://doi.org/10.1002/art.20019
Weinblatt ME, Keystone EC, Furst DE, Moreland LW, Weisman MH, Birbara CA, et al. 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; 48: 35-45.
DOI: https://doi.org/10.1002/art.10697
Moreland LW, Baumgartner SW, Schiff MH, Tindall EA, Fleischmann RM, Weaver AL, et al. Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med 1997; 337: 141-7.
DOI: https://doi.org/10.1056/NEJM199707173370301
Zhou H, Jang H, Fleischmann RM, Bouman-Thio E, Xu Z, Marini JC, et al. Pharmacokinetics and safety of golimumab, a fully human anti-TNF-alpha monoclonal antibody, in subjects with rheumatoid arthritis. J Clin Pharmacol 2007; 47: 383-96.
DOI: https://doi.org/10.1177/0091270006298188
Choy EH, Hazleman B, Smith M, Moss K, Lisi L, Scott DGI, et al. Efficacy of a novel PEGylated humanized anti-TNF fragment (CDP870) in patients with rheumatoid arthritis: a phase II double-blinded, randomized, dose-escalating trial. Rheumatology 2002; 41: 1133-7.
DOI: https://doi.org/10.1093/rheumatology/41.10.1133
Chinol M, Casalini P, Maggiolo M, Canevari S, Omodeo ES, Caliceti P, et al. Biochemical modifications of avidin improve pharmacokinetics and biodistribution, and reduce immunogenicity. Br J Cancer 1998; 78: 189-97.
DOI: https://doi.org/10.1038/bjc.1998.463
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: 1075-86.
DOI: https://doi.org/10.1002/art.21734
Schiff MH, Burmester GR, Kent JD, Pangan AL, Kupper H, Fitzpatrick SB, et al. Safety analyses of adalimumab (HUMIRA) in global clinical trials and US postmarketing surveillance of patients with rheumatoid arthritis. Ann Rheum Dis 2006; 65: 889-94.
DOI: https://doi.org/10.1136/ard.2005.043166
Wolfe F, Michaud K. Biologic treatment of rheumatoid arthritis and the risk of malignancy: analyses from a large US observational study. Arthritis Rheum 2007; 56: 2886-95.
DOI: https://doi.org/10.1002/art.22864
Jacobsson LT, Turesson C, Nilsson JA, Petersson IF, Lindqvist E, Saxne T, et al. Treatment with TNF blockers and mortality risk in patients with rheumatoid arthritis. Ann Rheum Dis 2007; 66: 670-5.
DOI: https://doi.org/10.1136/ard.2006.062497
Dixon WG, Watson K, Lunt M, Hyrich KL, Silman AJ, Symmons DP, et al. Rates of serious infection, including site-specific and bacterial intracellular infection, in rheumatoid arthritis patients receiving anti-tumor necrosis factor therapy: results from the British Society for Rheumatology Biologics Register. Arthritis Rheum 2006; 54: 2368-76.
DOI: https://doi.org/10.1002/art.21978
Iannone F, Gremese E, Atzeni F, Biasi D, Botsios C, Cipriani P, et al. Longterm retention of tumor necrosis factor-α inhibitor therapy in a large italian cohort of patients with rheumatoid arthritis from the GISEA registry: an appraisal of predictors. J Rheumatol 2012; 39: 1179-84.
DOI: https://doi.org/10.3899/jrheum.111125
Scherlinger M, Langlois E, Germain V, Schaeverbeke T. Acceptance rate and sociological factors involved in the switch from originator to biosimilar etanercept (SB4). Semin Arthritis Rheum 2019; 48: 927-32.
DOI: https://doi.org/10.1016/j.semarthrit.2018.07.005
Tweehuysen L, Huiskes VJB, van den Bemt BJF, Vriezekolk JE, Teerenstra S, van den Hoogen FHJ, et al. Open-label, non-mandatory transitioning from originator etanercept to biosimilar SB4: six-month results from a controlled cohort study. Arthritis Rheumatol 2018; 70: 1408-18.
DOI: https://doi.org/10.1002/art.40516
Kravvariti E, Kitas GD, Mitsikostas DD, Sfikakis PP. Nocebos in rheumatology: emerging concepts and their implications for clinical practice. Nat Rev Rheumatol 2018; 14: 727-40.
DOI: https://doi.org/10.1038/s41584-018-0110-9
Faasse K, Petrie KJ. The nocebo effect: patient expectations and medication side effects. Postgrad Med J 2013; 89: 540-6.
DOI: https://doi.org/10.1136/postgradmedj-2012-131730
Sakellariou G, Scirè CA, Zambon A, Caporali R, Montecucco C. Performance of the 2010 classification criteria for rheumatoid arthritis: a systematic literature review and a meta-analysis. PLoS One 2013; 8: e56528.
DOI: https://doi.org/10.1371/journal.pone.0056528
Rudwaleit M, van der Heijde D, Landewé R, Listing J, Akkoc N, Brandt J, et al. The development of assessment of spondyloarthritis international society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 2009; 68: 777-83.
DOI: https://doi.org/10.1136/ard.2009.108233
Rudwaleit M, van der Heijde D, Landewé R, Akkoc N, Brandt J, Chou CT, et al. The assessment of spondyloarthritis international society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis 2011; 70: 25-31.
DOI: https://doi.org/10.1136/ard.2010.133645
Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H, et al. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 2006; 54: 2665-73.
DOI: https://doi.org/10.1002/art.21972
Smolen JS, Landewé RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A, 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: 685-99.
DOI: https://doi.org/10.1136/annrheumdis-2019-216655
Dranitsaris G, Amir E, Dorward K. Biosimilars of biological drug therapies: regulatory, clinical and commercial considerations. Drugs 2011; 71: 1527-36.
DOI: https://doi.org/10.2165/11593730-000000000-00000
Sanchez-Piedra C, Hernández Miguel MV, Manero J, Roselló R, Sánchez-Costa JT, Rodríguez-Lozano C, et al. Objectives and methodology of BIOBADASER phase iii. Reumatol Clin (Engl Ed) 2019; 15: 229-36. [Article in English, Spanish].
DOI: https://doi.org/10.1016/j.reumae.2017.08.005
Odinet JS, Day CE, Cruz JL, Heindel GA. The Biosimilar Nocebo Effect? A systematic review of double-blinded versus open-label studies. J Manag Care Spec Pharm 2018; 24: 952-9.
DOI: https://doi.org/10.18553/jmcp.2018.24.10.952
Cho IH, Lee N, Song D, Jung SY, Bou-Assaf G, Sosic Z, et al. Evaluation of the structural, physicochemical, and biological characteristics of SB4, a biosimilar of etanercept. MAbs 2016; 8: 1136-55.
DOI: https://doi.org/10.1080/19420862.2016.1193659
Kaur P, Chow V, Zhang N, Moxness M, Kaliyaperumal A, Markus R. A randomised, single-blind, single-dose, three-arm, parallel-group study in healthy subjects to demonstrate pharmacokinetic equivalence of ABP 501 and adalimumab. Ann Rheum Dis 2017; 76: 526-33.
DOI: https://doi.org/10.1136/annrheumdis-2015-208914
Bruni C, Bitti R, Nacci F, Cometi L, Tofani L, Bartoli F, et al. Efficacy and safety of switching from reference adalimumab to SB5 in a real-life cohort of inflammatory rheumatic joint diseases. Clin Rheumatol 2021; 40: 85-91.
DOI: https://doi.org/10.1007/s10067-020-05199-w
Jawaheer D, Olsen J, Hetland ML. Sex differences in response to anti-tumor necrosis factor therapy in early and established rheumatoid arthritis - results from the DANBIO registry. J Rheumatol 2012; 39: 46-53.
DOI: https://doi.org/10.3899/jrheum.110548
Saevarsdottir S, Rezaei H, Geborek P, Petersson I, Ernestam S, Albertsson K, et al. Current smoking status is a strong predictor of radiographic progression in early rheumatoid arthritis: results from the SWEFOT trial. Ann Rheum Dis 2015; 74: 1509-14.
DOI: https://doi.org/10.1136/annrheumdis-2013-204601
Kearsley-Fleet L, Rokad A, Tsoi MF, Zhao SS, Lunt M, BSRBR-RA Contributors Group, et al. Etanercept originator versus etanercept biosimilar for the treatment of rheumatoid arthritis as a first biologic: results from the BSRBR-RA. Rheumatology 2023; kead127.
DOI: https://doi.org/10.1093/rheumatology/kead127
Larid G, Baudens G, Dandurand A, Coquerelle P, Goeb V, Guyot MH, et al. Differential retention of adalimumab and etanercept biosimilars compared to originator treatments: results of a retrospective French multicenter study. Front Med 2022; 9: 989514.
DOI: https://doi.org/10.3389/fmed.2022.989514
How to Cite
Gioia, C., Picchianti Diamanti, A. ., Perricone, R., Chimenti, M., Afeltra, A., Navarini, L., … Di Franco, M. . (2023). Anti-tumor necrosis factor α: originators <i>versus</i> biosimilars, comparison in clinical response assessment in a multicenter cohort of patients with inflammatory arthropathies. Reumatismo, 75(4). https://doi.org/10.4081/reumatismo.2023.1602
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