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A Comparative Study to Assess the Efficacy, Safety, and Immunogenicity of YLB113 and the Etanercept Reference Product for the Treatment of Patients with Rheumatoid Arthritis.

ABSTRACT: INTRODUCTION:YLB113 is a biosimilar of the reference product (RP), etanercept, under development for treatment of patients with moderate-to-severe rheumatoid arthritis (RA) and other approved indications. A phase 3 study was conducted in Europe, Japan, and India to compare the efficacy, safety, and immunogenicity of YLB113 with the RP over a treatment period of 52 weeks. METHODS:Overall, 528 patients with moderate-to-severe RA receiving concomitant methotrexate were randomized to receive a once-weekly, subcutaneous dose of 50 mg YLB113 or the RP. The primary endpoint was ACR20 response rate at week 24, with similarity confirmed if the 95% confidence interval (CI) for YLB113 and the RP was within the range of - 15 to 15%. Safety and immunogenicity endpoints were assessed to week 52. RESULTS:Based on the European analysis, in the full analysis set, ACR20 response at week 24 was 83.3% and 88.5% for YLB113 and the RP, respectively. Responses were within the predefined clinical equivalence margin. The sensitivity analysis in the per protocol set revealed a similar proportion of subjects exhibiting ACR20 response at week 24 between groups, with a difference of - 5.1% (95% CI - 11.07 to 0.81). The incidence of treatment-emergent adverse events was comparable between groups, and the incidence of antidrug antibody development to week 24 favored YLB113 (0.8 vs. 8.3%). CONCLUSIONS:This study demonstrated biosimilarity of YLB113 to the RP regarding efficacy, safety, and immunogenicity in patients with moderate-to-severe RA. Based on the same mechanism of action, biosimilarity could be extrapolated to other therapeutic indications approved for etanercept. TRIAL REGISTRATION:EudraCT Number: 2015-002,809-12.

SUBMITTER: Yamanaka H

PROVIDER: S-EPMC7021908 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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A Comparative Study to Assess the Efficacy, Safety, and Immunogenicity of YLB113 and the Etanercept Reference Product for the Treatment of Patients with Rheumatoid Arthritis.

Yamanaka Hisashi H Kamatani Naoyuki N Tanaka Yoshiya Y Hibino Toshihiko T Drescher Edit E Sánchez-Bursón Juan J Rettenbacher Manfred M Bhatia Girish G Gadve Snehal S Shah Chirag C Bakhle Dhananjay D

Rheumatology and therapy 20191212 1

<h4>Introduction</h4>YLB113 is a biosimilar of the reference product (RP), etanercept, under development for treatment of patients with moderate-to-severe rheumatoid arthritis (RA) and other approved indications. A phase 3 study was conducted in Europe, Japan, and India to compare the efficacy, safety, and immunogenicity of YLB113 with the RP over a treatment period of 52 weeks.<h4>Methods</h4>Overall, 528 patients with moderate-to-severe RA receiving concomitant methotrexate were randomized to ...[more]

PMID: 31833011

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Project description:Background: Although with the application of etanercept biosimilars in the field of rheumatoid arthritis, the evidences of their efficacy, safety, and immunogenicity are still limited. We conducted this meta-analysis to evaluate the efficacy, safety and immunogenicity of etanercept biosimilars for treating active rheumatoid arthritis compared to reference biologics (Enbrel®). Methods: PubMed, Embase, Central, and ClinicalTrials.gov were searched for randomized controlled trials of etanercept biosimilars treated in adult patients diagnosed with rheumatoid arthritis from their earliest records to 15 August 2022. The outcomes included ACR20, ACR50, and ACR70 response rate at different time points from FAS or PPS, adverse events, and proportion of patients developed anti-drug antibodies. The risk of bias of each included study was assessed using the revised Cochrane Risk of Bias in Randomised Trials tool, and the certainty of evidence was rated according to the Grading of Recommendation Assessment, Development, and Evaluation. Results: Six RCTs with 2432 patients were included in this meta-analysis. Etanercept biosimilars showed more benefits in ACR50 at 24 weeks from PPS [5 RCTs, OR = 1.22 (1.01, 1.47), p = 0.04, I 2 = 49%, high certainty], ACR50 at 1 year from PPS [3 RCTs, OR = 1.43 (1.10, 1.86), p < 0.01, I 2 = 0%, high certainty] or FAS [2 RCTs, OR = 1.36 (1.04, 1.78), p = 0.03, I 2 = 0%, high certainty], and ACR70 at 1 year from PPS [3 RCTs, OR = 1.32 (1.01, 1.71), p = 0.04, I 2 = 0%, high certainty]. In terms of other outcomes about efficacy, safety, and immunogenicity, the results showed that there was no significant difference between etanercept biosimilars and reference biologics, and the certainty of evidences ranged from low to moderate. Conclusion: Etanercept biosimilars showed more benefits in ACR50 response rate at 1 year than reference biologics (Enbrel®), other outcomes for clinical efficacy, safety, and immunogenicity of etanercept biosimilars were comparable with originator in patients with rheumatoid arthritis. Systematic Review Registration: PROSPERO, identifier CRD42022358709.

Project description:BackgroundABP 710 is being developed as a biosimilar to infliximab reference product (RP). Analytical similarity and pharmacokinetic equivalence between the two have been previously demonstrated. Here we report results from a comparative clinical study that evaluated the efficacy and safety of ABP 710 relative to the RP in patients with rheumatoid arthritis (RA).MethodsIn this multicenter, randomized, double-blind, 50-week equivalence study, patients with moderate to severe active RA despite methotrexate received 3-mg/kg infusions of ABP 710 or RP at predetermined intervals based on initial randomization and then with re-randomization at week 22. The primary endpoint was response difference (RD) of ACR20 at week 22, with clinical equivalence evaluated based on 90% CI of - 15%, 15%. Secondary endpoints included Disease Activity Score 28-joint count C-reactive protein (DAS28-CRP), ACR20, ACR50, and ACR70 across time, as well as safety and immunogenicity assessments.ResultsA total of 558 patients were randomized for the initial treatment (ABP 710 n = 279; RP n = 279). The estimated RD of ACR20 at week 22 was 9.37% with 90% CI (2.67%, 15.96%). The lower bound was within the pre-specified criteria, thus confirming non-inferiority; the upper bound exceeded the pre-specified criteria by 0.96% such that superiority could not be ruled out statistically. In a post hoc analysis with adjustment for random imbalance in baseline factors, the CI of RD was narrowed (0.75%, 13.62%). Changes from baseline in DAS28-CRP as well as ACR20, ACR50, and ACR70 response rates across time and hybrid ACR evaluations were similar for the initial and initial/re-randomized treatment groups. Adverse events and incidence of anti-drug antibodies were similar between treatment groups.ConclusionsThese efficacy and safety results support similarity with no clinically meaningful differences between ABP 710 and infliximab RP. Although we were unable to statistically confirm non-superiority, post hoc analysis was supportive of non-superiority. DAS28-CRP, ACR20, ACR50, ACR70, and hybrid ACR evaluations over the entire study were consistently comparable as were safety and immunogenicity.Trial registrationClinicalTrials.gov. Identifier: NCT02937701. Registered August 30, 2016.

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:BackgroundBiosimilar etanercept presents itself as an innovative therapeutic opportunity for inflammatory and autoimmune diseases, however, its efficacy, safety, and immunogenicity in relation to the reference biological agent for the treatment of rheumatoid arthritis is still questioned. With this in mind, this study aimed to verify the efficacy, safety, and immunogenicity of the use of the biosimilar etanercept in relation to the reference biologic in patients over 18 years of age with rheumatoid arthritis.MethodsA systematic review with meta-analysis was performed in accordance with the parameters of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) selecting only Phase III randomized clinical trials. The search strategy was constructed with the MeSH terms "Etanercept", "Biological Products", "Arthritis, Rheumatoid", "Biosimilar Pharmaceuticals" and was performed in Medline via PubMed, Embase, the Cochrane Library, Web of Science, EBSCO and Lilacs in January 2023. The analysis measures were relative risk (RR) for dichotomous data and mean difference (MD) for continuous data. The statistical analysis for preparing meta-analyses was developed by the Review Manager 5.1.4 software.ResultsThis systematic review selected 6 eligible studies with a sample population of n = 2355. The main efficacy outcomes showed that both drugs did not present statistically significant differences in ACR20, ACR50, and ACR70 responses within 6 months (RR 1.00; 95% CI = 0.94 to 1.07; RR 1.09; 95% CI = 0.94 to 1.26; RR 1.04; 95% CI = 0.82 to 1.31, respectively), with I2 ranging from 55 to 63% and 0.04 ≤ P ≥ 0.08. Adverse events were mostly mild or moderate, and serious adverse events were not statistically significant. Regarding immunogenicity, only 5.4% of the ADA-positive biosimilar group had positive neutralizing antibodies.ConclusionsThus, this review found that biosimilar etanercept had efficacy, safety, and immunogenicity similar to those for the biological reference.Systematic review registrationThis systematic review was registered on the PROSPERO platform under number CRD42020166610.

Dataset Information

A Comparative Study to Assess the Efficacy, Safety, and Immunogenicity of YLB113 and the Etanercept Reference Product for the Treatment of Patients with Rheumatoid Arthritis.

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A Comparative Study to Assess the Efficacy, Safety, and Immunogenicity of YLB113 and the Etanercept Reference Product for the Treatment of Patients with Rheumatoid Arthritis.

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