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Long-term efficacy, safety and immunogenicity in patients with rheumatoid arthritis continuing on an etanercept biosimilar (LBEC0101) or switching from reference etanercept to LBEC0101: an open-label extension of a phase III multicentre, randomised, double-blind, parallel-group study.

ABSTRACT: BACKGROUND:To evaluate the long-term efficacy, safety and immunogenicity of continuing LBEC0101; the etanercept (ETN) biosimilar; or switching from the ETN reference product (RP) to LBEC0101 in patients with rheumatoid arthritis (RA). METHODS:This multicentre, single-arm, open-label extension study enrolled patients who had completed a 52-week randomised, double-blind, parallel phase III trial of LBEC0101 vs ETN-RP. Patients treated with ETN-RP during the randomised controlled trial switched to LBEC0101; those treated with LBEC0101 continued to receive LBEC0101 in this study. LBEC0101 (50?mg) was administered subcutaneously once per week for 48?weeks with a stable dose of methotrexate. Efficacy, safety and immunogenicity of LBEC0101 were assessed up to week 100. RESULTS:A total of 148 patients entered this extension study (70 in the maintenance group and 78 in the switch group). The 28-joint disease activity scores (DAS28)-erythrocyte sedimentation rate (ESR) were maintained in both groups from week 52 to week 100 (from 3.068 to 3.103 in the maintenance group vs. from 3.161 to 3.079 in the switch group). ACR response rates at week 100 for the maintenance vs. switch groups were 79.7% vs. 83.3% for ACR20, 65.2% vs. 66.7% for ACR50 and 44.9% vs. 42.3% for ACR70. The incidence of adverse events and the proportion of patients with newly developed antidrug antibodies were similar in the maintenance and switch groups (70.0% and 70.5%, 1.4% and 1.3%, respectively). CONCLUSIONS:Administration of LBEC0101 showed sustained efficacy and acceptable safety in patients with RA after continued therapy or after switching from ETN-RP to LBEC0101. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02715908 . Registered 22 March 2016.

SUBMITTER: Park MC

PROVIDER: S-EPMC6528252 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Long-term efficacy, safety and immunogenicity in patients with rheumatoid arthritis continuing on an etanercept biosimilar (LBEC0101) or switching from reference etanercept to LBEC0101: an open-label extension of a phase III multicentre, randomised, double-blind, parallel-group study.

Park Min-Chan MC Matsuno Hiroaki H Kim Jinseok J Park Sung-Hwan SH Lee Sang-Heon SH Park Yong-Beom YB Lee Yun Jong YJ Lee Sang-Il SI Park Won W Sheen Dong Hyuk DH Choe Jung-Yoon JY Choi Chan-Bum CB Hong Seung-Jae SJ Suh Chang-Hee CH Lee Shin-Seok SS Cha Hoon-Suk HS Yoo Bin B Hur Jin-Wuk JW Kim Geun-Tae GT Yoo Wan-Hee WH Baek Han Joo HJ Shin Kichul K Shim Seung Cheol SC Yang Hyung-In HI Kim Hyun Ah HA Park Kyung-Su KS Choi In Ah IA Lee Jisoo J Tomomitsu Masato M Shin Seonghye S Lee Jiyoon J Song Yeong Wook YW

Arthritis research & therapy 20190521 1

<h4>Background</h4>To evaluate the long-term efficacy, safety and immunogenicity of continuing LBEC0101; the etanercept (ETN) biosimilar; or switching from the ETN reference product (RP) to LBEC0101 in patients with rheumatoid arthritis (RA).<h4>Methods</h4>This multicentre, single-arm, open-label extension study enrolled patients who had completed a 52-week randomised, double-blind, parallel phase III trial of LBEC0101 vs ETN-RP. Patients treated with ETN-RP during the randomised controlled tri ...[more]

PMID: 31113455

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Project description:IntroductionIn 2016, SB4 (Benepali®) became the first etanercept (ETN) biosimilar to obtain marketing authorisation in Europe. Despite robust analytical and clinical comparisons, outstanding questions remain on SB4 use in routine practice.MethodsA systematic search for publications on real-world evidence of SB4 effectiveness, safety and drug survival was undertaken using search terms (SB4 OR Benepali OR biosimilar etanercept OR innovator etanercept) in the BIOSIS® Toxicology, BIOSIS Previews®, Embase® and MEDLINE® databases up to 17 January 2019.ResultsOf 959 articles identified, eight journal articles, two journal letters and 23 congress abstracts were selected on criteria of original real-world evidence with a clinical focus. As expected with real-world evidence, quality scoring showed that the evidence had high external validity but lower internal validity. A total of 13,552 patients were described across nine European countries and all approved SB4 indications: 2499 were ETN-naïve and 11,053 switched from reference ETN to SB4 (switchers). Switch acceptance rates (a combination of clinicians offering and patients accepting initiation on SB4) ranged between 51.6% and 99.0%; patient support programmes positively contributed to acceptance. Disease activity was generally similar pre- and post-switch (typically 3-month timeframe). Retention rates across studies were at least 75% (up to 12 months follow-up). No new safety signals were identified. Differences in discontinuation rates versus historic controls reported in some studies may have been influenced by differences in treatment practices, lack of clinician confidence and nocebo effects.ConclusionNearly 2500 ETN-naïve patients have been initiated on SB4 and outcomes are similar to those patients receiving reference ETN. Overall this systematic review of real-world evidence provides additional reassurance that SB4 is as effective and safe as reference ETN in both switched and naïve patients.FundingBiogen International GmbH.

Project description:Background/objectiveREFLECTIONS B538-02 is a randomized, double-blind comparative study of the adalimumab (ADL) biosimilar PF-06410293, (ADL-PF), and reference ADL sourced from the European Union (ADL-EU) in patients with active RA. Therapeutic equivalence was demonstrated based on ACR20 responses at week 12 (primary endpoint). We report long-term safety, immunogenicity, and efficacy of ADL-PF in patients who continued ADL-PF treatment throughout 78 weeks or who switched from ADL-EU to ADL-PF at week 26 or week 52.MethodsEligible patients (2010 ACR/EULAR RA diagnosis criteria for ≥ 4 months; inadequate response to MTX, ≤ 2 doses non-ADL biologic), stratified by geographic regions were initially randomized (1:1) in treatment period 1 (TP1) to ADL-PF or ADL-EU (40 mg subcutaneously, biweekly), both with MTX (10-25 mg/week). At week 26 (start of TP2), patients receiving ADL-EU were re-randomized to remain on ADL-EU or transition to ADL-PF for 26 weeks. At week 52 (start of TP3), all patients received open-label treatment with ADL-PF for 26 weeks and were followed after last treatment dose to week 92. To evaluate maintenance of response after switching or remaining on ADL-PF, ACR20, DAS28-4(CRP), and other measures of clinical response/remission were assessed through week 78 as secondary endpoints. Three groups were evaluated: biosimilar, week 26 switch, and week 52 switch.ResultsOverall, 507 patients participated in TP3. ACR20 response rates at week 52 were 88.4%, 88.2%, and 87.6% for the biosimilar, week 26, and week 52 switch groups, respectively. ACR20 response rates and DAS28-4(CRP) scores were sustained and comparable across groups in TP3. Incidence of treatment-emergent adverse events (AEs) during TP3 and follow-up was 42.6% (biosimilar), 37.0% (week 26 switch), and 50.8% (week 52 switch); 3 (0.6%) patients (all week 52 switch) reported treatment-related serious AEs. ADL-PF was generally well tolerated, with a comparable safety profile across groups. Overall, incidences of patients with anti-drug antibodies in TP3 and follow-up were comparable among groups (46.1%, 46.5%, and 54.2%, respectively).ConclusionsThere were no clinically meaningful differences in safety, immunogenicity, and efficacy for patients who were maintained on ADL-PF for 78 weeks and those who had switched from ADL-EU at week 26 or week 52.Trial registrationClinicalTrials.gov , NCT02480153. First posted on June 24, 2015; EU Clinical Trials Register; EudraCT number: 2014-000352-29. Start date, October 27, 2014.

Project description:BackgroundSandoz etanercept (SDZ ETN; GP2015) is an etanercept biosimilar with equivalent efficacy and comparable safety and immunogenicity to reference etanercept (ETN) in patients with moderate-to-severe chronic plaque-type psoriasis.MethodsEQUIRA was a phase III, double-blind study conducted in patients with moderate-to-severe rheumatoid arthritis and inadequate response to disease-modifying anti-rheumatic drugs. Eligible patients were randomized 1:1 to receive subcutaneous 50 mg SDZ ETN or ETN, once-weekly, for 24 weeks. At week 24, patients with at least moderate EULAR response in the SDZ ETN group continued SDZ ETN treatment, and those in the ETN group were switched to receive 50 mg SDZ ETN, for up to 48 weeks. Patients received concomitant methotrexate at a stable dose (10-25 mg/week) and folic acid (≥ 5 mg/week). Equivalence between SDZ ETN and ETN for change from baseline in disease activity score including 28 joint count C-reactive protein (DAS28-CRP) at week 24 (primary endpoint) and comparable safety and immunogenicity profile of SDZ ETN and ETN have previously been demonstrated at week 24. Herein, we present the 48-week results of the study after a single switch from ETN to its biosimilar at week 24.ResultsThe least squares mean (standard error) change in DAS28-CRP from baseline up to week 48 was comparable between "continued SDZ ETN" (- 2.90 [0.12], n = 148) and "switched to SDZ ETN" (- 2.78 [0.13], n = 131) groups. The proportion of patients achieving EULAR good/moderate responses based on DAS28-erythrocyte sedimentation rate and ACR20/50/70 response rates were comparable between the two groups. The proportion of patients with at least one treatment-emergent adverse event was 42.9% in the "continued SDZ ETN" and 38.0% in the "switched to SDZ ETN" groups. Serious adverse events occurred in 4 patients in each of the two groups. After week 24, none of the patients in the switched group developed anti-drug antibodies (ADAs), while 4 patients in the continued SDZ ETN group had single-event, very low titer, non-neutralizing ADAs detected.ConclusionsThe 48-week results from the EQUIRA study demonstrate that switch from ETN to SDZ ETN in patients with moderate-to-severe rheumatoid arthritis does not impact the efficacy, safety, or immunogenicity of etanercept.Trial registrationEudraCT number 2012-002009-23 , Registered 19 April 2012-prospectively registered.

Project description:BackgroundMultiple switches (transitions) between biosimilars of the same reference biologic are now a reality, and they are expected to become more common in the future as more biosimilars enter the market. Switching between two biosimilars of the same reference biologic is generally driven by affordability, formulary requirements, or the relocation/travel of the patient. Evidence of whether switching between biosimilars of the same reference biologic provides similar safety and efficacy profiles is reviewed here.MethodsA systematic search was undertaken using electronic databases (to December 2021): Biosis, Embase, MEDLINE, and EBM Reviews/Cochrane Database of Systematic Reviews via Ovid. Publications were evaluated for effectiveness and/or safety data linked to switching from one biosimilar to another.ResultsThe systematic search yielded 982 citations. After eliminating duplicates, 626 citations remained for the initial title/abstract screening phase. Following the initial screening, 240 records were chosen; more thorough examination yielded 35 citations. After comprehensive screening and expert advice, 23 studies were selected, of which 13 were published in peer-reviewed journals; the remainder have been published as abstracts. Overall, 3657 patients were included in these studies. All studies were observational in nature; no randomized clinical trials were identified. The studies were heterogeneous in size, design, and endpoints. Across the studies, data are provided on safety, effectiveness, immunogenicity, pharmacokinetics, patient retention, patient and physician perceptions, and drug-use patterns. The majority of studies examined switches between biosimilar infliximabs, although switches between biosimilar adalimumabs, etanercepts, and rituximabs were also identified. Two use-pattern studies and one case report were also detected and are discussed.ConclusionWithin the limitations of this systematic review, available data suggests that biosimilar-to-biosimilar switching is a safe and effective clinical practice, although it is not covered by current health authority regulations or guidance. No reduction in effectiveness or increase in adverse events was detected in biosimilar-to-biosimilar switching studies conducted to date.

Project description:OBJECTIVE:To compare the efficacy, serum drug concentrations, immunogenicity, and safety of FKB327 with the adalimumab reference product (RP) in combination with methotrexate in patients with moderate-to-severe, active rheumatoid arthritis (RA). METHODS:Patients were randomized 1:1 in a double-blind study (NCT02260791), received 40?mg of FKB327 or RP by subcutaneous injection every other week for 24?weeks (Period I), then re-randomized 2:1, remaining on the same study drug or switching to the other up to week 54 in an open-label extension (Period II, NCT02405780). Efficacy was evaluated using American College of Rheumatology (ACR20) response rate difference at week 24 with equivalence margins of ±?13% and -?12% to +?15% using 95% and 90% confidence intervals (CIs), respectively. Efficacy, serum drug concentrations, immunogenicity, and safety were compared at week 54. RESULTS:A total of 730 patients were randomized in Period I (n?=?367 FKB327, n?=?363 RP), and 645 transitioned to Period II (n?=?216 FKB327-FKB327, n?=?108 FKB327-RP, n?=?108 RP-FKB327, n?=?213 RP-RP). At week 24, ACR20 response rates were 74.1% with FKB327 versus 75.7% with RP. 95% and 90% CI of the response rate difference were -?7.9 to 4.7% and -?7.3 to 3.6%, respectively, meeting predefined equivalence margins. The ACR20 response rate remained over 70% of patients to week 54 with all treatment sequences. In Period I, mean trough serum drug concentrations were slightly higher for patients receiving FKB327 than those receiving RP. Mean concentrations were stable over time and reflected steady state in Period II. The proportions of patients with samples positive for neutralizing antidrug antibodies (ADAs) were comparable (57.7% with FKB327 vs. 55.5% with RP) at week 24, and no consistent difference in ADA were seen between continuous and switched treatments in Period II. Efficacy was slightly reduced in the small proportion of patients with high ADA titers in all treatment groups. No clinically significant differences were observed in the incidence of commonly reported treatment-emergent adverse events between the treatments across Periods I and II. CONCLUSION:FKB327 was equivalent to RP in clinical efficacy and demonstrated comparable safety and immunogenicity in patients with moderate-to-severe RA. No effect of switching between FKB327 and RP was observed. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02260791, Registered 29 July 2014. ClinicalTrials.gov, NCT02405780, Registered 17 July 2015.

Dataset Information

Long-term efficacy, safety and immunogenicity in patients with rheumatoid arthritis continuing on an etanercept biosimilar (LBEC0101) or switching from reference etanercept to LBEC0101: an open-label extension of a phase III multicentre, randomised, double-blind, parallel-group study.

Publications

Long-term efficacy, safety and immunogenicity in patients with rheumatoid arthritis continuing on an etanercept biosimilar (LBEC0101) or switching from reference etanercept to LBEC0101: an open-label extension of a phase III multicentre, randomised, double-blind, parallel-group study.

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