OBJECTIVES: SB4 (Benepali, Brenzys) is a biosimilar of reference etanercept (ETN). In a randomised, double-blind, 52-week study, SB4 demonstrated comparable efficacy and safety to ETN in patients with rheumatoid arthritis (RA). The open-label extension period evaluated long-term efficacy, safety and immunogenicity when continuing SB4 versus switching from ETN to SB4. METHODS: In the randomised, double-blind phase, patients received weekly subcutaneous administration of 50 mg SB4 or ETN with background methotrexate for up to 52 weeks. Patients in the Czech Republic and Poland who completed the 52-week visit were enrolled in the open-label extension period and received SB4 for 48 additional weeks. Efficacy, safety and immunogenicity were assessed up to week 100. RESULTS: Of 245 patients entering the extension period, 126 continued to receive SB4 (SB4/SB4) and 119 switched to SB4 (ETN/SB4). American College of Rheumatology (ACR) response rates were sustained and comparable between SB4/SB4 and ETN/SB4 with ACR20 response rates at week 100 of 77.9% and 79.1%, respectively. Other efficacy results, including radiographic progression, were also comparable between the groups. After week 52, rates of treatment-emergent adverse events were 47.6% (SB4/SB4) and 48.7% (ETN/SB4); one patient/group developed non-neutralising antidrug antibodies. No cases of active tuberculosis or injection-site reactions were reported during the extension period. One patient (SB4/SB4) died of hepatic cancer. CONCLUSIONS: SB4 was effective and well tolerated over 2 years in patients with RA. Efficacy, safety and immunogenicity were comparable between the SB4/SB4 and ETN/SB4 groups, showing no risk associated with switching patients from ETN to SB4. TRIAL REGISTRATION NUMBER: NCT01895309; 2012-005026-30.

Arthritis Research Leeds Institute of Rheumatic and Musculoskeletal Medicine University of Leeds Leeds UK

Clinical Sciences Division Samsung Bioepis Co Ltd Incheon Republic of Korea

NIHR Leeds Musculoskeletal Biomedical Research Unit Leeds Teaching Hospitals NHS Trust Leeds UK

Rheumatology Centrum Terapii Wspolczesnej J M Jasnorzewska sp komandytowo akcyjna Bialystok Poland

Rheumatology Institute of Rheumatology Prague Czech Republic

Rheumatology Medicome Sp z o o Oswiecim Poland

Rheumatology NZOZ Medica Pro Familia Sp z o o Warsaw Poland

Rheumatology Poznan University of Medical Sciences Poznan Poland

Rheumatology Poznanski Osrodek Medyczny NOVAMED Pultusk Poland

Rheumatology Revmacentrum MUDr Mostera sro Brno Czech Republic

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Scott LJ. Etanercept: a review of its use in autoimmune inflammatory diseases. Drugs 2014;74:1379–410. 10.1007/s40265-014-0258-9 PubMed DOI

Enbrel®. Etanercept. Thousand Oaks, CA: Immunex Corporation, 2016.

Enbrel® (etanercept). Product characteristics 2016.

Cho IH, Lee N, Song D, et al. . Evaluation of the structural, physicochemical, and biological characteristics of SB4, a biosimilar of etanercept. MAbs 2016;8:1136–55. 10.1080/19420862.2016.1193659 PubMed DOI PMC

Lee YJ, Shin D, Kim Y, et al. . A randomized phase l pharmacokinetic study comparing SB4 and etanercept reference product (Enbrel) in healthy subjects. Br J Clin Pharmacol 2016;82:64–73. 10.1111/bcp.12929 PubMed DOI PMC

Emery P, Vencovský J, Sylwestrzak 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. 10.1136/annrheumdis-2015-207588 PubMed DOI PMC

Vencovsky J, Sylwestrzak A, Leszczynski P, et al. . A phase III, randomized, double-blind clinical study comparing SB4, an etanercept biosimilar, with etanercept reference product (Enbrel) in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy (52-week results) [abstract]. Arthritis Rheumatol 2015;67:2444–6.

Benepali®(etanercept). Product characteristics 2016.

Brenzys™ (etanercept). Product monograph 2016.

van der Heijde D. How to read radiographs according to the sharp/van der Heijde method. J Rheumatol 2000;27:261–3. PubMed

Emery P, Breedveld F, van der Heijde D, et al. . Two-year clinical and radiographic results with combination etanercept-methotrexate therapy versus monotherapy in early rheumatoid arthritis: a two-year, double-blind, randomized study. Arthritis Rheum 2010;62:674–82. 10.1002/art.27268 PubMed DOI

Keystone EC, Pope JE, Thorne JC, et al. . Two-year radiographic and clinical outcomes from the Canadian methotrexate and etanercept outcome study in patients with rheumatoid arthritis. Rheumatology 2016;55:327–34. 10.1093/rheumatology/kev338 PubMed DOI PMC

van der Heijde D, Klareskog L, Landewé R, et al. . Disease remission and sustained halting of radiographic progression with combination etanercept and methotrexate in patients with rheumatoid arthritis. Arthritis Rheum 2007;56:3928–39. 10.1002/art.23141 PubMed DOI

Dore RK, Mathews S, Schechtman J, et al. . The immunogenicity, safety, and efficacy of etanercept liquid administered once weekly in patients with rheumatoid arthritis. Clin Exp Rheumatol 2007;25:40–6. PubMed

Klareskog L, Gaubitz M, Rodríguez-Valverde V, et al. . Assessment of long-term safety and efficacy of etanercept in a 5-year extension study in patients with rheumatoid arthritis. Clin Exp Rheumatol 2011;29:238–47. PubMed

Weinblatt ME, Schiff MH, Ruderman EM, et al. . Efficacy and safety of etanercept 50 mg twice a week in patients with rheumatoid arthritis who had a suboptimal response to etanercept 50 mg once a week: results of a multicenter, randomized, double-blind, active drug-controlled study. Arthritis Rheum 2008;58:1921–30. 10.1002/art.23493 PubMed DOI

Yoo DH, Prodanovic N, Jaworski J, et al. . Efficacy and safety of CT-P13 (biosimilar infliximab) in patients with rheumatoid arthritis: comparison between switching from reference infliximab to CT-P13 and continuing CT-P13 in the PLANETRA extension study. Ann Rheum Dis 2017;76:355–63. 10.1136/annrheumdis-2015-208786 PubMed DOI PMC

Park W, Yoo DH, Miranda P, et al. . Efficacy and safety of switching from reference infliximab to CT-P13 compared with maintenance of CT-P13 in ankylosing spondylitis: 102-week data from the PLANETAS extension study. Ann Rheum Dis 2017;76:346–54. 10.1136/annrheumdis-2015-208783 PubMed DOI PMC

Jørgensen KK, Olsen IC, Goll GL, et al. . Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial. Lancet 2017;389:2304–16. 10.1016/S0140-6736(17)30068-5 PubMed DOI

Glintborg B, Sørensen IJ, Loft AG, et al. . A nationwide non-medical switch from originator infliximab to biosimilar CT-P13 in 802 patients with inflammatory arthritis: 1-year clinical outcomes from the DANBIO registry. Ann Rheum Dis 2017;76:1426–31. 10.1136/annrheumdis-2016-210742 PubMed DOI

Glintborg B, Sørensen IJ, Loft AG, et al. . Clinical outcomes from a nationwide non-medical switch from originator to biosimilar etanercept in patients with inflammatory arthritis after 5 months follow-up. Results from the Danbio registry. Ann Rheum Dis 2017;76:553. PubMed

Sampson HA, Muñoz-Furlong A, Campbell RL, et al. . Second symposium on the definition and management of anaphylaxis: summary report--Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol 2006;117:391–7. 10.1016/j.jaci.2005.12.1303 PubMed DOI

Switching From Reference Adalimumab to SB5 (Adalimumab Biosimilar) in Patients With Rheumatoid Arthritis: Fifty-Two-Week Phase III Randomized Study Results

Safety, immunogenicity and efficacy after switching from reference infliximab to biosimilar SB2 compared with continuing reference infliximab and SB2 in patients with rheumatoid arthritis: results of a randomised, double-blind, phase III transition study

52-week results of the phase 3 randomized study comparing SB4 with reference etanercept in patients with active rheumatoid arthritis

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NCT01895309