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

ABSTRACT: Objective:To compare the 52-week efficacy and safety of SB4 [an etanercept biosimilar] with reference etanercept (ETN) in patients with active RA. Methods:In a phase 3, randomized, double-blind, multicentre study, patients with moderate to severe RA despite MTX treatment were randomized to receive 50 mg/week of s.c. SB4 or ETN up to week 52. Efficacy assessments included ACR response rates, 28-joint DAS, Simplified and Clinical Disease Activity Indices and changes in the modified total Sharp score (mTSS). Safety and immunogenicity were also evaluated. Results:A total of 596 patients were randomized to receive either SB4 (n = 299) or ETN (n = 297) and 505 (84.7%) patients completed 52 weeks of the study. At week 52, the ACR20 response rates in the per-protocol set were comparable between SB4 (80.8%) and ETN (81.5%). All efficacy results were comparable between the two groups and they were maintained up to week 52. Radiographic progression was also comparable and the change from baseline in the mTSS was 0.45 for SB4 and 0.74 for ETN. The safety profile of SB4 was similar to that of ETN and the incidence of anti-drug antibody development up to week 52 was 1.0 and 13.2% in the SB4 and ETN groups, respectively. Conclusion:Efficacy including radiographic progression was comparable between SB4 and ETN up to week 52. SB4 was well tolerated and had a similar safety profile to that of ETN. Trial registration number:ClinicalTrials.gov NCT01895309, EudraCT 2012-005026-30.

SUBMITTER: Emery P

PROVIDER: S-EPMC5850652 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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

Emery Paul P Vencovský Jirí J Sylwestrzak Anna A Leszczynski Piotr P Porawska Wieslawa W Baranauskaite Asta A Tseluyko Vira V Zhdan Vyacheslav M VM Stasiuk Barbara B Milasiene Roma R Barrera Rodriguez Aaron Alejandro AA Cheong Soo Yeon SY Ghil Jeehoon J

Rheumatology (Oxford, England) 20171201 12

<h4>Objective</h4>To compare the 52-week efficacy and safety of SB4 [an etanercept biosimilar] with reference etanercept (ETN) in patients with active RA.<h4>Methods</h4>In a phase 3, randomized, double-blind, multicentre study, patients with moderate to severe RA despite MTX treatment were randomized to receive 50 mg/week of s.c. SB4 or ETN up to week 52. Efficacy assessments included ACR response rates, 28-joint DAS, Simplified and Clinical Disease Activity Indices and changes in the modified ...[more]

PMID: 28968793

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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:BackgroundThe aim was to analyze characteristics that predict remission induction and subsequent loss of remission in patients with moderately active rheumatoid arthritis (RA) who received full-dose combination etanercept plus methotrexate induction therapy followed by reduced-dose etanercept or etanercept withdrawal.MethodsPatients with Disease Activity Score based on 28-joint count (DAS28) >3.2 and ≤5.1 received open-label etanercept 50 mg once weekly (QW) plus methotrexate for 36 weeks. Those who achieved DAS28 low disease activity by 36 weeks were randomized to double-blind treatment with etanercept 50 mg or 25 mg QW plus methotrexate or placebo plus methotrexate for 52 weeks. All analyses were adjusted for the continuous baseline variables of their respective remission outcomes.ResultsYounger age, body mass index (BMI) <30 kg/m2, and lower Health Assessment Questionnaire (HAQ) score at baseline were significant predictors of week-36 remission (P < 0.05) based on DAS28, Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI). Baseline DAS28, SDAI, and CDAI were significantly predictive of all three remission endpoints (P < 0.05). For all three treatments, the strongest predictors of loss of DAS28 remission included failure to achieve sustained remission (DAS28 < 2.6 at weeks 12, 20, 28, and 36) with induction therapy, higher DAS28/SDAI/CDAI at randomization and at 1 month, increase in DAS28/SDAI/CDAI at 1 month, and increase in DAS28/CDAI/SDAI components and patient-reported outcomes (PROs) at 1 month. With the exception of not achieving sustained remission, very similar significant predictors were observed for loss of SDAI and CDAI remission.ConclusionThese findings suggest that patients with moderately active RA who are younger and have lower BMI, lower HAQ, and lower disease activity at baseline are most likely to achieve remission when receiving combination etanercept and methotrexate induction therapy. In addition, patients who fail to achieve sustained remission with induction therapy and those with worse disease activity and PROs at early time points after initiating maintenance therapy with a full-dose or reduced-dose etanercept-methotrexate regimen or methotrexate monotherapy are most likely to lose remission across all treatment arms. These findings may help guide clinicians' decision-making as they treat patients to remission and beyond.Trial registrationClinicalTrials.gov, NCT00565409 . Registered on 28 November 2007.

Project description:ObjectivesEtanercept biosimilars show comparable efficacy to their originators among biologic-naïve patients with RA in randomized controlled trials. Nationwide guidelines have obligated prescribing of etanercept biosimilars from 2016, resulting in significant cost savings. This analysis aimed to compare the effectiveness of etanercept originator vs etanercept biosimilar amongst biologic-naïve RA patients treated in routine clinical practice in the UK.MethodsBiologic-naïve RA patients starting etanercept in the British Society for Rheumatology Biologics Register in Rhematoid Arthritis (BSRBR-RA) cohort study from 2010 were included. Data collected at start of therapy includes patient demographics and disease activity. Follow-up data includes changes in disease activity and anti-rheumatic therapy. Six- and 12-month primary outcomes include DAS for 28-joints (DAS28) remission, EULAR response and minimal clinically important difference in function. Etanercept drug survival was assessed using Kaplan-Meier and Cox regression, including reasons for treatment withdrawal. Multiple imputation accounted for missing data. Propensity-decile adjustment was used to account for confounding by indication.ResultsA total of 1806 biologic-naïve RA patients started etanercept: 1009 originator, 797 biosimilar. At 6 and 12 months, the proportion of patients achieving DAS28 remission and EULAR response were similar between treatments. During follow-up, 19% of originator patients switched onto etanercept biosimilar. Patients were censored at time of switch. Patients on originator were no more likely to stop therapy vs biosimilar; 71% of originator and 76% of biosimilar patients remained on therapy at 1 year.ConclusionsIn one of the largest analyses of patients with RA, biologic-naïve RA patients treated with etanercept originator showed similar outcomes vs biosimilar using real-world data. Drug survival, and disease activity after 6 and 12 months of therapy, was similar between cohorts.

Dataset Information

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

Publications

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

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