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  • Tocilizumab combination therapy or monotherapy or methotrexate monotherapy in methotrexate-naive patients with early rheumatoid arthritis: 2-year clinical and radiographic results from the randomised, placebo-controlled FUNCTION trial

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Clinical and epidemiological research
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Tocilizumab combination therapy or monotherapy or methotrexate monotherapy in methotrexate-naive patients with early rheumatoid arthritis: 2-year clinical and radiographic results from the randomised, placebo-controlled FUNCTION trial
  1. Gerd R Burmester1,
  2. William F Rigby2,
  3. Ronald F van Vollenhoven3,
  4. Jonathan Kay4,
  5. Andrea Rubbert-Roth5,
  6. Ricardo Blanco6,
  7. Alysha Kadva7,
  8. Sophie Dimonaco8
  1. 1 Charité-Universitätsmedizin Berlin, Free University and Humboldt University of Berlin, Berlin, Germany
  2. 2 Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA
  3. 3 Karolinska Institute, Stockholm, Sweden
  4. 4 UMass Memorial Medical Center and University of Massachusetts Medical School, Worcester, Massachusetts, USA
  5. 5 University of Cologne, Cologne, Germany
  6. 6 Hospital Universitario Marqués de Valdecilla, Santander, Spain
  7. 7 Genentech, South San Francisco, California, USA
  8. 8 Roche Products Ltd., Welwyn Garden City, UK
  1. Correspondence to Dr Gerd R Burmester, Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Free University and Humboldt University of Berlin, Charitéplatz 1, Berlin 10117, Germany; gerd.burmester{at}charite.de

Abstract

Objective Investigate whether the efficacy and safety of intravenous tocilizumab (TCZ) demonstrated at week 52 in patients with early rheumatoid arthritis (RA) are maintained to week 104.

Methods Methotrexate (MTX)-naive patients with early progressive RA were randomly assigned to double-blind 4 mg/kg TCZ+MTX, 8 mg/kg TCZ+MTX, 8 mg/kg TCZ+placebo or placebo+MTX for 104 weeks. Patients not receiving 8 mg/kg TCZ and not achieving Disease Activity Score-28 joints (DAS28-erythrocyte sedimentation rate (ESR)) ≤3.2 at week 52 switched to escape therapy (8 mg/kg TCZ+MTX). Analyses were exploratory.

Results Intent-to-treat and safety populations included 1157 and 1153 patients, respectively. DAS28-ESR remission (<2.6) rates were maintained from weeks 52 to 104 (eg, 8 mg/kg TCZ+MTX, 49.3% to 47.6%). Placebo+MTX and 4 mg/kg TCZ+MTX escape patients' week 104 response rates were 51.4% and 30.5%, respectively. Inhibition of radiographic progression was maintained with 8 mg/kg TCZ (eg, 8 mg/kg TCZ+MTX mean (SD) change from baseline in modified total Sharp score: 0.13 (1.28), week 52; 0.19 (2.08), week 104). The safety profile of TCZ was consistent with that of previous reports.

Conclusions Patients with early RA treated with TCZ monotherapy or TCZ+MTX maintained clinical benefits during their second year of treatment with no new safety signals.

Trial registration number: NCT01007435; Results.

  • DMARDs (biologic)
  • Early Rheumatoid Arthritis
  • Methotrexate

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) 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/4.0/

https://doi.org/10.1136/annrheumdis-2016-210561

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    Footnotes

    • Handling editor Tore K Kvien

    • Contributors GRB and WFR contributed to the conception and design of the study. GRB, WFR, RFvV, JK, AR-R and RB contributed to data acquisition. GRB, WFR, RFvV, JK, AR-R, RB, AK and SD analysed and interpreted the data. GRB, WFR, JK, AK and SD drafted the manuscript. All authors revised the manuscript critically for important intellectual content. All authors contributed to, reviewed and approved the final manuscript. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

    • Funding This study was funded by Roche. Funding for manuscript preparation was provided by F. Hoffmann-La Roche Ltd.

    • Competing interests GRB has received honoraria from Roche for lectures and consulting. WFR reports grants and personal fees from Roche outside the submitted work. RFvV reports grants from Roche during the conduct of the study; grants from AbbVie, Amgen, BMS, GSK, Pfizer, Roche, UCB; and personal fees from AbbVie, Biotest, BMS, Celgene, Crescendo, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, and Vertex outside the submitted work. JK reports grants and personal fees from AbbVie, Eli Lilly and Company, Genentech, Pfizer, Roche Laboratories and UCB; and personal fees from Amgen, Boehringer Ingelheim GmbH, Bristol-Myers Squibb Company, Crescendo Bioscience, Epirus Biopharmaceuticals, GlaxoSmithKline, Hospira, Janssen Biotech, Merck Sharp & Dohme, Novartis Pharmaceuticals, Regeneron Pharmaceuticals, Samsung Bioepis and Sandoz outside the submitted work. AR-R reports personal fees from Roche and Chugai during the conduct of the study and personal fees from Pfizer, Lilly, BMS, AbbVie, MSD, UCB, Janssen, Sanofi and Boehringer outside the submitted work. RB reports grants from Roche, Merck Sharp & Dohme and AbbVie outside the submitted work. AK is an employee of Genentech. SD is an employee of Roche Products.

    • Patient consent Obtained.

    • Ethics approval This trial was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice and was approved by the Institutional Review Board/Independent Ethics Committee governing each site.

    • Provenance and peer review Not commissioned; externally peer reviewed.