Long-term efficacy and safety in patients with rheumatoid arthritis continuing on SB4 or switching from reference etanercept to SB4

Abstract

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.

Keywords: DMARDs (biologic); TNF-alpha; anti-TNF; rheumatoid arthritis; treatment.

Conflict of interest statement

Competing interests: All authors received funding for clinical research from Samsung Bioepis. PE received consulting fees; JV, AS, PL, WP, BS, JH, and ZM received research grants and SYC and JG are full-time employee of Samsung Bioepis. In addition, PE reports receiving grant/research support from AbbVie and Pfizer and consultancy fees from AbbVie, Bristol-Myers Squibb, Pfizer, UCB, Merck Sharp & Dohme, Roche, Novartis, Takeda and Lilly; JV served on speakers bureaus for UCB, Pfizer, AbbVie and Merck Sharp & Dohme; PL received grant/research support from Roche, Merck Sharp & Dohme, Janssen, Novo-Nordisk, UCB, Pfizer, Novartis, GlaxoSmithKline, Bristol-Myers Squibb, served as paid instructor for Novo-Nordisk and served on speakers bureaus for Merck Sharp & Dohme, UCB, Roche and Amgen.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1

Patient disposition. AE, adverse event; ETN, reference etanercept.

Figure 2

American College of Rheumatology (ACR) response rates up to week 100 (extended population). ACR20/50/70=American College of Rheumatology 20%/50%/70% response criteria; ETN, reference etanercept.

Figure 3

Cumulative probability of mTSS change from baseline at week 100 (extended population). Data based on patients with available radiographic assessment results at each visit. ETN, reference etanercept; mTSS, modified Total Sharp Score.