A randomised, double-blind trial to demonstrate bioequivalence of GP2013 and reference rituximab combined with methotrexate in patients with active rheumatoid arthritis.

Abstract:

OBJECTIVES:The aim of this report is to demonstrate pharmacokinetic (PK) and pharmacodynamic (PD) equivalence as well as similar efficacy, safety and immunogenicity between GP2013, a biosimilar rituximab, and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA) with inadequate response or intolerance to tumour necrosis factor inhibitor (TNFi) treatment. METHODS:In this multinational, randomised, double-blind, parallel-group study, 312 patients with active disease despite prior TNFi therapy were randomised to receive GP2013 or either the EU (RTX-EU) or the US (RTX-US) reference product, along with methotrexate (MTX) and folic acid. The primary endpoint was the area under the serum concentration-time curve from study drug infusion to infinity (AUC0-inf). Additional PK and PD parameters, along with efficacy, immunogenicity and safety outcomes were also assessed up to week 24. RESULTS:The 90% CI of the geometric mean ratio of the AUCs were within the bioequivalence limits of 80% to 125% for all three comparisons; GP2013 versus RTX-EU: 1.106 (90% CI 1.010 to 1.210); GP2013 versus RTX-US: 1.012 (90% CI 0.925 to 1.108); and RTX-EU versus RTX-US: 1.093 (90% CI 0.989 to 1.208). Three-way PD equivalence of B cell depletion was also demonstrated. Efficacy, safety and immunogenicity profiles were similar between GP2013 and RTX. CONCLUSIONS:Three-way PK/PD equivalence of GP2013, RTX-EU and RTX-US was demonstrated. Efficacy, safety and immunogenicity profiles were similar between GP2013 and RTX. TRIAL REGISTRATION NUMBER:NCT01274182; Results.

journal_name

Ann Rheum Dis

authors

Smolen JS,Cohen SB,Tony HP,Scheinberg M,Kivitz A,Balanescu A,Gomez-Reino J,Cen L,Zhu P,Shisha T

doi

10.1136/annrheumdis-2017-211281

subject

Has Abstract

pub_date

2017-09-01 00:00:00

pages

1598-1602

issue

9

eissn

0003-4967

issn

1468-2060

pii

annrheumdis-2017-211281

journal_volume

76

pub_type

杂志文章,多中心研究,随机对照试验
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    authors: Moser B,Willimann K

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    doi:10.1136/ard.2005.049924

    authors: Suárez A,López P,Gómez J,Gutiérrez C

    更新日期:2006-11-01 00:00:00

  • Naproxen in juvenile chronic polyarthritis.

    abstract::Naproxen at 10 mg per kg body weight was compared with aspirin at 80 mg per kg body weight in children suffering from juvenile chronic polyarthritis. It was found to be as effective as aspirin, with certainly no more and possibly fewer gastrointestinal side effects. A long-term tolerance study up to 12 months confirme...

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    doi:10.1136/ard.38.2.152

    authors: Moran H,Hanna DB,Ansell BM,Hall M,Engler C

    更新日期:1979-04-01 00:00:00

  • Rapid development of a tophus following ipsilateral hemiparesis.

    abstract::An 85 year old man with a longstanding history of non-tophaceous gout developed a single large tophus, unassociated with inflammation, on his paretic leg over a six week period following an acute hemiplegia. The rapidity of tophus formation, its localisation to the paretic limb, and the apparent blunting of the acute ...

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    pub_type: 杂志文章

    doi:10.1136/ard.52.4.308

    authors: Donegan CF,Berman P,Doherty M

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    doi:10.1136/ard.51.2.177

    authors: van der Heijde DM,van't Hof MA,van Riel PL,van Leeuwen MA,van Rijswijk MH,van de Putte LB

    更新日期:1992-02-01 00:00:00

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    doi:10.1136/ard.53.10.671

    authors: Lioté F,Osterland CK

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    doi:10.1136/ard.2008.106658

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    更新日期:2010-02-01 00:00:00

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章,多中心研究

    doi:10.1136/ard.2010.137422

    authors: Salmon-Ceron D,Tubach F,Lortholary O,Chosidow O,Bretagne S,Nicolas N,Cuillerier E,Fautrel B,Michelet C,Morel J,Puéchal X,Wendling D,Lemann M,Ravaud P,Mariette X,RATIO group.

    更新日期:2011-04-01 00:00:00

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章,评审

    doi:10.1136/ard.2003.019125

    authors: Knight A,Askling J,Granath F,Sparen P,Ekbom A

    更新日期:2004-10-01 00:00:00

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    doi:10.1136/ard.46.12.883

    authors: Bucknall R,Leirisalo-Repo M,Laitinen O,Jones JV

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    authors: Vossenaar ER,Radstake TR,van der Heijden A,van Mansum MA,Dieteren C,de Rooij DJ,Barrera P,Zendman AJ,van Venrooij WJ

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    doi:10.1136/ard.53.11.768

    authors: Taylor DJ,Cheung NT,Dawes PT

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    doi:10.1136/ard.44.2.130

    authors: Lowthian PJ,Calin A

    更新日期:1985-02-01 00:00:00

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    pub_type: 杂志文章,实务指引

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    更新日期:2007-01-01 00:00:00

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    pub_type: 杂志文章

    doi:10.1136/ard.51.6.707

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    更新日期:1992-06-01 00:00:00

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章,多中心研究

    doi:10.1136/ard.2007.086348

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/annrheumdis-2013-204309

    authors: Banka S,Cain SA,Carim S,Daly SB,Urquhart JE,Erdem G,Harris J,Bottomley M,Donnai D,Kerr B,Kingston H,Superti-Furga A,Unger S,Ennis H,Worthington J,Herrick AL,Merry CL,Yue WW,Kielty CM,Newman WG

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章,meta分析,评审

    doi:10.1136/annrheumdis-2013-204494

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    更新日期:2015-04-01 00:00:00

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.62.7.659

    authors: Slart RH,Jager PL,Poot L,Piers DA,Tervaert JW,Stegeman CA

    更新日期:2003-07-01 00:00:00

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    pub_type: 杂志文章

    doi:10.1136/ard.2008.099713

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.50.5.328

    authors: Livneh A,Sharma K,Sewell KL,Keiser HD

    更新日期:1991-05-01 00:00:00

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    pub_type: 杂志文章

    doi:10.1136/ard.45.6.475

    authors: Henriksson K,Uvnäs-Moberg K,Nord CE,Johansson C,Gullberg R

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    doi:10.1136/ard.46.4.327

    authors: Andrews FJ,Morris CJ,Kondratowicz G,Blake DR

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    doi:10.1136/ard.40.2.182

    authors: Yurdakul S,Yazici H,Tüzüner N,Aytac S,Müftüoğlu AU

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    doi:10.1136/ard.49.10.788

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    journal_title:Annals of the rheumatic diseases

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    doi:10.1136/annrheumdis-2018-213645

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    pub_type: 杂志文章,评审

    doi:10.1136/ard.2007.078337

    authors: Neurath MF

    更新日期:2007-11-01 00:00:00

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    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.2004.033688

    authors: Rhodes LA,Conaghan PG,Radjenovic A,Grainger AJ,Emery P,McGonagle D

    更新日期:2005-09-01 00:00:00