Table Info

Table 2.

TNFα-i biosimilar clinical trial examples [20–24, 29–31]

Biosimilar compared to reference	Patients on biosimilar (n)	Patients on reference (n)	Biosimilar ACR20 (%)	Reference ACR20 (%)
PF-06410293 (adalimumab-afzb); Abrilada^®	297	300	68.7	72.7
MSB11022 (adalimumab-aacf); Idacio^®	147	145	85.7	82.8
FKB327 (adalimumab-fkjp); Hulio^®	366	362	77	79.3
BI 695501 (adalimumab-adbm); Cyltezo^®	321	318	68.8	64.5
BI 695501 (adalimumab-adbm); Cyltezo^®	297	300	83.2	77.7
SB5 (adalimumab-bwws); Hadlima^®	271	273	67.2	67.4
ABP 501 (adalimumab-atto); Amjevita^®	264	261	73.5	72.4
SB4 (etanercept-ykro); Eticovo^®	299	297	80.8	81.5
GP2015 (etanercept-szzs); Elrezi^®	186	190	88.8	93.6

TNFα-i: tumor necrosis factor α inhibitor; ACR20: American College of Rheumatology 20% improvement

Declarations

Author contributions

LAS: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. JSA: Investigation, Writing—original draft.

Conflicts of interest

Both authors declare no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

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References

Møller-Bisgaard S, Hørslev-Petersen K, Ejbjerg B, Hetland ML, Christensen R, Ørnbjerg LM, et al. Effect of initiating biologics compared to intensifying conventional DMARDs on clinical and MRI outcomes in established rheumatoid arthritis patients in clinical remission: Secondary analyses of the IMAGINE-RA trial. Scand J Rheumatol. 2022;51:268–78. [DOI] [PubMed]

Fautrel B, Kedra J, Rempenault C, Juge P, Drouet J, Avouac J, et al. 2024 update of the recommendations of the French Society of Rheumatology for the diagnosis and management of patients with rheumatoid arthritis. Joint Bone Spine. 2024;91:105790. [DOI] [PubMed]

Romanowska-Próchnicka K, Felis-Giemza A, Olesińska M, Wojdasiewicz P, Paradowska-Gorycka A, Szukiewicz D. The Role of TNF-α and Anti-TNF-α Agents during Preconception, Pregnancy, and Breastfeeding. Int J Mol Sci. 2021;22:2922. [DOI] [PubMed] [PMC]

Fraenkel L, Bathon JM, England BR, Clair EWS, Arayssi T, Carandang K, et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2021;73:924–39. [DOI] [PubMed] [PMC]

Hollan I, Ronda N, Dessein P, Agewall S, Karpouzas G, Tamargo J, et al. Lipid management in rheumatoid arthritis: a position paper of the Working Group on Cardiovascular Pharmacotherapy of the European Society of Cardiology. Eur Heart J Cardiovasc Pharmacother. 2020;6:104–14. [DOI] [PubMed]

Halacoglu J, Shea LA. Cardiovascular Risk Assessment and Therapeutic Implications in Rheumatoid Arthritis. J Cardiovasc Transl Res. 2020;13:878–90. [DOI] [PubMed]

Karpouzas GA, Ormseth SR, van Riel PLCM, Gonzalez-Gay MA, Corrales A, Rantapää-Dahlqvist S, et al. Biological use influences the impact of inflammation on risk of major adverse cardiovascular events in rheumatoid arthritis. RMD Open. 2024;10:e004546. [DOI] [PubMed] [PMC]

Strangfeld A, Richter A. How do register data support clinical decision-making? Z Rheumatol. 2015;74:119–24. [DOI] [PubMed]

Xbrane to regain full rights to BIIB801, a proposed biosimilar referencing CIMZIA^® [Internet]. XBRANE BioPharma; [cited 2025 Jan 21]. Available from: https://xbrane.com/en/mfn_news/xbrane-to-regain-full-rights-to-biib801-a-proposed-biosimilar-referencing-cimzia/

10.

Rašková M, Lacina L, Kejík Z, Venhauerová A, Skaličková M, Kolář M, et al. The Role of IL-6 in Cancer Cell Invasiveness and Metastasis-Overview and Therapeutic Opportunities. Cells. 2022;11:3698. [DOI] [PubMed] [PMC]

11.

Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT; Investigators ATACHF; Anti-TNF Therapy Against Congestive Heart Failure Investigators. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation. 2003;107:3133–40. [DOI] [PubMed]

12.

Roubille C, Richer V, Starnino T, McCourt C, McFarlane A, Fleming P, et al. The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis. Ann Rheum Dis. 2015;74:480–9. [DOI] [PubMed] [PMC]

13.

Agca R, Heslinga SC, Rollefstad S, Heslinga M, McInnes IB, Peters MJL, et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis. 2017;76:17–28. [DOI] [PubMed]

14.

Cojocaru M, Cojocaru IM, Silosi I. Multiple autoimmune syndrome. Maedica (Bucur). 2010;5:132–4. [PubMed] [PMC]

15.

Sepriano A, Kerschbaumer A, Bergstra SA, Smolen JS, Heijde Dvd, Caporali R, et al. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2023;82:107–18. [DOI] [PubMed]

16.

Huang Y, Agarwal SK, Chen H, Chatterjee S, Johnson ML, Aparasu RR. Real-world Comparative Effectiveness of Methotrexate-based Combinations for Rheumatoid Arthritis: A Retrospective Cohort Study. Clin Ther. 2023;45:e177–86. [DOI] [PubMed]

17.

18.

Mpofu S, Fatima F, Moots RJ. Anti-TNF-alpha therapies: they are all the same (aren’t they?). Rheumatology (Oxford). 2005;44:271–3. [DOI] [PubMed]

19.

Goel N, Chance K. Biosimilars in rheumatology: understanding the rigor of their development. Rheumatology (Oxford). 2017;56:187–97. [DOI] [PubMed] [PMC]

20.

Fleischmann RM, Alvarez DF, Bock AE, Cronenberger C, Vranic I, Zhang W, et al. Long-term efficacy, safety, and immunogenicity of the adalimumab biosimilar, PF-06410293, in patients with rheumatoid arthritis after switching from reference adalimumab (Humira^®) or continuing biosimilar therapy: week 52-92 data from a randomized, double-blind, phase 3 trial. Arthritis Res Ther. 2021;23:248. [DOI] [PubMed] [PMC]

21.

Fleischmann RM, Alten R, Pileckyte M, Lobello K, Hua SY, Cronenberger C, et al. A comparative clinical study of PF-06410293, a candidate adalimumab biosimilar, and adalimumab reference product (Humira^®) in the treatment of active rheumatoid arthritis. Arthritis Res Ther. 2018;20:178. [DOI] [PubMed] [PMC]

22.

Martínez-Vidal MP, Fernández-Carballido C, Otero-Varela L, Ruiz FJM, Pérez-Vera Y, Arija SM, et al. Long-Term Survival of Subcutaneous Biosimilar Tumor Necrosis Factor Inhibitors Compared to Originators: Results From a Multicenter Prospective Registry. J Rheumatol. 2024;51:877–83. [DOI] [PubMed]

23.

Pekhenko V, Udovitskiy V, Barbukho O. Efficacy, safety and immunogenicity of the biosimilar etanercept compared to the reference formulation original etanercept in patients with rheumatoid arthritis: An open-label, randomized, comparative, multicenter study. Medicine (Baltimore). 2024;103:e39060. [DOI] [PubMed] [PMC]

24.

Emery P, Vencovský J, Sylwestrzak A, Leszczyński P, Porawska W, Baranauskaite A, et al. A phase III randomised, double-blind, parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis. 2017;76:51–7. [DOI] [PubMed] [PMC]

25.

Biosimilar biologic drugs in Canada: Fact Sheet [Internet]. Government of Canada; [cited 2024 Dec 6]. Available from: https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/applications-submissions/guidance-documents/fact-sheet-biosimilars.html

26.

Scallon B, Cai A, Solowski N, Rosenberg A, Song X, Shealy D, et al. Binding and functional comparisons of two types of tumor necrosis factor antagonists. J Pharmacol Exp Ther. 2002;301:418–26. [DOI] [PubMed]

27.

Billmeier U, Dieterich W, Neurath MF, Atreya R. Molecular mechanism of action of anti-tumor necrosis factor antibodies in inflammatory bowel diseases. World J Gastroenterol. 2016;22:9300–13. [DOI] [PubMed] [PMC]

28.

Jha A, Upton A, Dunlop WCN, Akehurst R. The Budget Impact of Biosimilar Infliximab (Remsima^®) for the Treatment of Autoimmune Diseases in Five European Countries. Adv Ther. 2015;32:742–56. [DOI] [PubMed] [PMC]

29.

Lee YH, Song GG. Comparative efficacy and safety of adalimumab biosimilars and adalimumab in patients with rheumatoid arthritis presenting an insufficient response to methotrexate: a network meta-analysis. Z Rheumatol. 2023;82:64–70. [DOI] [PubMed]

30.

Popescu CC, Mogoșan CD, Enache L, Codreanu C. Comparison of Efficacy and Safety of Original and Biosimilar Adalimumab in Active Rheumatoid Arthritis in a Real-World National Cohort. Medicina (Kaunas). 2022;58:1851. [DOI] [PubMed] [PMC]

31.

García-Miguel J, Komsalova LY, Arnaiz CM, Alegre-Sancho JJ, Polo JG, Torrente-Segarra V, et al. POS0661 Clinical outcomes of switching to adalimumab biosimilar (MSB11022) in patients with rheumatoid arthritis: RESTART Spanish Registry. Annals of the Rheumatic Diseases. 2024;83:808–9. [DOI]

32.

33.

Singh JA, Hossain A, Mudano AS, Tanjong Ghogomu E, Suarez-Almazor ME, Buchbinder R, et al. Biologics or tofacitinib for people with rheumatoid arthritis naive to methotrexate: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2017;5:CD012657. [DOI] [PubMed] [PMC]

34.

Gulacsi L, Brodszky V, Baji P, Rencz F, Pentek M. The rituximab biosimilar CT-P10 in rheumatology and cancer: a budget impact analysis in 28 European countries. Adv Ther. 2017;34:1128–44. Erratum in: Adv Ther. 2017;34:1234. [DOI] [PubMed] [PMC]

35.

Scott LJ. Tocilizumab: A Review in Rheumatoid Arthritis. Drugs. 2017;77:1865–79. Erratum in: Drugs. 2018;78:285. [DOI] [PubMed] [PMC]

36.

Jones G, Sebba A, Gu J, Lowenstein MB, Calvo A, Gomez-Reino JJ, et al. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis. 2010;69:88–96. [DOI] [PubMed] [PMC]

37.

Dougados M, Kissel K, Sheeran T, Tak PP, Conaghan PG, Mola EM, et al. Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate responders: 24-week symptomatic and structural results of a 2-year randomised controlled strategy trial in rheumatoid arthritis (ACT-RAY). Ann Rheum Dis. 2013;72:43–50. [DOI] [PubMed] [PMC]

38.

Gabay C, Emery P, van Vollenhoven R, Dikranian A, Alten R, Pavelka K, et al.; ADACTA Study Investigators. Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. Lancet. 2013;381:1541–50. [DOI] [PubMed]

39.

Best JH, Vlad SC, Pei J. Comparative Cost per Response for 4 Clinical Endpoints with Tocilizumab Monotherapy vs Adalimumab Monotherapy in a Head-to-Head Randomized Double-Blind Superiority Trial (ADACTA) in Patients with Rheumatoid Arthritis. Rheumatol Ther. 2020;7:165–71. [DOI] [PubMed] [PMC]

40.

Wang W, Zhou H, Liu L. Side effects of methotrexate therapy for rheumatoid arthritis: A systematic review. Eur J Med Chem. 2018;158:502–16. [DOI] [PubMed]

41.

Łukasik A, Kozicka K, Wojas-Pelc A. The influence of methotrexate on hair loss while using immunomodulatory doses. Pol Merkur Lekarski. 2019;46:77–9. [PubMed]

42.

Arthritis Medication and Hair Loss [Internet]. Arthritis Foundation; [cited 2024 Dec 10]. Available from: https://www.arthritis.org/health-wellness/treatment/treatment-plan/disease-management/arthritis-medication-hair-loss

43.

Rivellese F, Surace AEA, Goldmann K, Sciacca E, Çubuk C, Giorli G, et al.; R4RA collaborative group. Rituximab versus tocilizumab in rheumatoid arthritis: synovial biopsy-based biomarker analysis of the phase 4 R4RA randomized trial. Nat Med. 2022;28:1256–68. [DOI] [PubMed] [PMC]

44.

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 (Lausanne). 2022;9:989514. [DOI] [PubMed] [PMC]

45.

Giuseppe DD, Lindstrom U, Bower H, Delcoigne B, Frisell T, Chatzidionysiou K, et al. Comparison of treatment retention of originator vs biosimilar products in clinical rheumatology practice in Sweden. Rheumatology (Oxford). 2022;61:3596–605. [DOI] [PubMed] [PMC]