Article Text

PDF

Extended report
Efficacy and safety of ascending methotrexate dose in combination with adalimumab: the randomised CONCERTO trial
  1. Gerd-Rűdiger Burmester1,
  2. Alan J Kivitz2,
  3. Hartmut Kupper3,
  4. Udayasankar Arulmani4,
  5. Stefan Florentinus5,
  6. Sandra L Goss4,
  7. Suchitrita S Rathmann4,
  8. Roy M Fleischmann6
  1. 1Department of Rheumatology and Clinical Immunology, Charité—University Medicine Berlin, Berlin, Germany
  2. 2Altoona Center for Clinical Research, Duncansville, Pennsylvania, USA
  3. 3AbbVie Deutschland GmbH & Co KG, Ludwigshafen, Germany
  4. 4AbbVie Inc, North Chicago, Illinois, USA
  5. 5AbbVie, Rungis, France
  6. 6University of Texas Southwestern, Dallas, Texas, USA
  1. Correspondence to Dr Gerd-Rűdiger Burmester, Department of Rheumatology and Clinical Immunology, Charité—University Medicine Berlin, Charitéplatz 1, Berlin 10117, Germany; gerd.burmester{at}charite.de

Abstract

Objective CONCERTO was a randomised, double-blind, parallel-armed study of methotrexate (MTX) in combination with adalimumab to assess whether an increasing trend of efficacy and decreased safety exists when increasing MTX dose in patients with early rheumatoid arthritis (RA).

Methods Early, biologic and MTX-naive RA patients (N=395) were evenly randomised to open-label adalimumab (40 mg every other week) plus weekly blinded 2.5, 5, 10 or 20 mg MTX for 26 weeks. Clinical, radiographic and functional outcomes were analysed using two-sided linear trend tests or one-way analysis of covariance.

Results Statistically significant increasing trends were observed in the proportion of patients achieving the primary endpoint, 28-joint count disease activity score with C reactive protein (DAS28(CRP)) <3.2 (42.9%, 44.0%, 56.6% and 60.2% for 2.5, 5, 10 or 20 mg/week MTX, respectively), DAS28(CRP) <2.6 and American College of Rheumatology 50/70/90 responses with increasing doses of MTX in combination with adalimumab. No statistical differences in minimal clinically important differences in physical function were detected. Statistically significant trends for achieving low disease activity and remission were demonstrated with increasing MTX dose by validated clinical indices; differences comparing 10 and 20 mg MTX were minimal. Adalimumab serum concentrations increased with ascending dose up to 10 mg MTX. More patients experienced infectious adverse events with increasing MTX dose.

Conclusions Increasing doses of MTX in combination with adalimumab demonstrated a statistically significant trend in improved clinical outcomes that mimicked the adalimumab pharmacokinetic profile. In early RA patients initiating adalimumab combination therapy, efficacy of 10 and 20 mg/week MTX appeared equivalent.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

Statistics from Altmetric.com

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

    Files in this Data Supplement:

  • Lay summary

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.