Literature DB >> 16935912

Selective costimulation modulation using abatacept in patients with active rheumatoid arthritis while receiving etanercept: a randomised clinical trial.

Michael Weinblatt1, Michael Schiff, Allan Goldman, Joel Kremer, Michael Luggen, Tracy Li, Dalei Chen, Jean-Claude Becker.   

Abstract

OBJECTIVE: To investigate the efficacy and safety of abatacept in combination with etanercept in patients with active rheumatoid arthritis during a 1-year, randomised, placebo-controlled, double-blind phase, followed by an open-label, long-term extension (LTE).
METHODS: Patients continued etanercept (25 mg twice weekly) and were randomised to receive abatacept 2 mg/kg (n = 85) or placebo (n = 36). As the effective dose of abatacept was established as 10 mg/kg in a separate trial, all patients received abatacept 10 mg/kg and etanercept during the LTE.
RESULTS: A total of 121 patients were randomised; 80 completed double-blind treatment and entered the LTE. During double-blind treatment, the difference in the percentage of patients achieving the primary end point (modified American College of Rheumatology (ACR) 20 response at 6 months) was not significant between groups (48.2% v 30.6%; p = 0.072). At 1 year, no notable changes in modified ACR responses were observed. Subsequent to the dosing change, similar modified ACR responses were seen during the LTE. Significant improvements in quality of life were observed with abatacept and etanercept versus placebo and etanercept in five of the eight short-form 36 subscales at 1 year. More abatacept and etanercept-treated patients experienced serious adverse events (SAEs) at 1 year than patients receiving placebo and etanercept (16.5% v 2.8%), with 3.5% v 0% experiencing serious infections.
CONCLUSION: The combination of abatacept (at a dose of 2 mg/kg during the double-blind phase and 10 mg/kg during the LTE) and etanercept was associated with an increase in SAEs, including serious infections, with limited clinical effect. On the basis of the limited efficacy findings and safety concerns, abatacept in combination with etanercept should not be used for rheumatoid arthritis treatment.

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Year:  2006        PMID: 16935912      PMCID: PMC1798511          DOI: 10.1136/ard.2006.055111

Source DB:  PubMed          Journal:  Ann Rheum Dis        ISSN: 0003-4967            Impact factor:   19.103


  9 in total

Review 1.  Determining clinically important differences in health status measures: a general approach with illustration to the Health Utilities Index Mark II.

Authors:  G Samsa; D Edelman; M L Rothman; G R Williams; J Lipscomb; D Matchar
Journal:  Pharmacoeconomics       Date:  1999-02       Impact factor: 4.981

2.  Safety of the selective costimulation modulator abatacept in rheumatoid arthritis patients receiving background biologic and nonbiologic disease-modifying antirheumatic drugs: A one-year randomized, placebo-controlled study.

Authors:  M Weinblatt; B Combe; A Covucci; R Aranda; J C Becker; E Keystone
Journal:  Arthritis Rheum       Date:  2006-09

3.  The American College of Rheumatology 1991 revised criteria for the classification of global functional status in rheumatoid arthritis.

Authors:  M C Hochberg; R W Chang; I Dwosh; S Lindsey; T Pincus; F Wolfe
Journal:  Arthritis Rheum       Date:  1992-05

4.  The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.

Authors:  F C Arnett; S M Edworthy; D A Bloch; D J McShane; J F Fries; N S Cooper; L A Healey; S R Kaplan; M H Liang; H S Luthra
Journal:  Arthritis Rheum       Date:  1988-03

5.  Treatment of rheumatoid arthritis with the selective costimulation modulator abatacept: twelve-month results of a phase iib, double-blind, randomized, placebo-controlled trial.

Authors:  Joel M Kremer; Maxime Dougados; Paul Emery; Patrick Durez; Jean Sibilia; William Shergy; Serge Steinfeld; Elizabeth Tindall; Jean-Claude Becker; Tracy Li; Isaac F Nuamah; Richard Aranda; Larry W Moreland
Journal:  Arthritis Rheum       Date:  2005-08

6.  Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial.

Authors:  L W Moreland; M H Schiff; S W Baumgartner; E A Tindall; R M Fleischmann; K J Bulpitt; A L Weaver; E C Keystone; D E Furst; P J Mease; E M Ruderman; D A Horwitz; D G Arkfeld; L Garrison; D J Burge; C M Blosch; M L Lange; N D McDonnell; M E Weinblatt
Journal:  Ann Intern Med       Date:  1999-03-16       Impact factor: 25.391

7.  Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate.

Authors:  Mark C Genovese; Stanley Cohen; Larry Moreland; Deborah Lium; Sean Robbins; Richard Newmark; Pirow Bekker
Journal:  Arthritis Rheum       Date:  2004-05

8.  Costimulatory blockade in patients with rheumatoid arthritis: a pilot, dose-finding, double-blind, placebo-controlled clinical trial evaluating CTLA-4Ig and LEA29Y eighty-five days after the first infusion.

Authors:  Larry W Moreland; Rieke Alten; Filip Van den Bosch; Thierry Appelboom; Marc Leon; Paul Emery; Stanley Cohen; Michael Luggen; William Shergy; Isaac Nuamah; Jean-Claude Becker
Journal:  Arthritis Rheum       Date:  2002-06

9.  Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig.

Authors:  Joel M Kremer; Rene Westhovens; Marc Leon; Eduardo Di Giorgio; Rieke Alten; Serge Steinfeld; Anthony Russell; Maxime Dougados; Paul Emery; Isaac F Nuamah; G Rhys Williams; Jean-Claude Becker; David T Hagerty; Larry W Moreland
Journal:  N Engl J Med       Date:  2003-11-13       Impact factor: 91.245

  9 in total
  86 in total

Review 1.  Dual targeting strategies with bispecific antibodies.

Authors:  Roland E Kontermann
Journal:  MAbs       Date:  2012-03-01       Impact factor: 5.857

Review 2.  Safety of biologic therapy in rheumatoid arthritis.

Authors:  Robert S Woodrick; Eric M Ruderman
Journal:  Nat Rev Rheumatol       Date:  2011-10-11       Impact factor: 20.543

Review 3.  Pharmacotherapy: concepts of pathogenesis and emerging treatments. Co-stimulation and T cells as therapeutic targets.

Authors:  Alison M Gizinski; David A Fox; Sujata Sarkar
Journal:  Best Pract Res Clin Rheumatol       Date:  2010-08       Impact factor: 4.098

Review 4.  [Infectious complications of biologic therapy in patients with rheumatoid arthritis].

Authors:  D Meyer-Olson; K Hoeper; R E Schmidt
Journal:  Z Rheumatol       Date:  2010-12       Impact factor: 1.372

Review 5.  Infectious complications associated with monoclonal antibodies and related small molecules.

Authors:  Edsel Maurice T Salvana; Robert A Salata
Journal:  Clin Microbiol Rev       Date:  2009-04       Impact factor: 26.132

6.  [Recommedations for the use of abatacept in patients with rheumatoid arthritis].

Authors:  K Krüger; M Gaubitz
Journal:  Z Rheumatol       Date:  2008-11       Impact factor: 1.372

Review 7.  [Combination of biologics : where do we stand?].

Authors:  P Härle
Journal:  Z Rheumatol       Date:  2013-11       Impact factor: 1.372

Review 8.  The current state of the art for biological therapies and new small molecules in inflammatory bowel disease.

Authors:  Sudarshan Paramsothy; Adam K Rosenstein; Saurabh Mehandru; Jean-Frederic Colombel
Journal:  Mucosal Immunol       Date:  2018-06-15       Impact factor: 7.313

Review 9.  Biologics and heart failure in rheumatoid arthritis: are we any wiser?

Authors:  Maria I Danila; Nivedita M Patkar; Jeffrey R Curtis; Kenneth G Saag; Gim Gee Teng
Journal:  Curr Opin Rheumatol       Date:  2008-05       Impact factor: 5.006

Review 10.  Biologic treatments for systemic rheumatic diseases.

Authors:  Y Shirota; G G Illei; N P Nikolov
Journal:  Oral Dis       Date:  2008-02-14       Impact factor: 3.511

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