Open Access Highly Accessed Research article

Association of serum markers with improvement in clinical response measures after treatment with golimumab in patients with active rheumatoid arthritis despite receiving methotrexate: results from the GO-FORWARD study

Sudha Visvanathan19, Mahboob U Rahman1102, Edward Keystone34, Mark Genovese5, Lars Klareskog6, Elizabeth Hsia12, Michael Mack1, Jacqui Buchanan117, Michael Elashoff8 and Carrie Wagner1*

Author Affiliations

1 Centocor Research and Development, Inc., 200 Great Valley Parkway, Malvern, PA 19355, USA

2 University of Pennsylvania School of Medicine, 3620 Hamilton Walk, Philadelphia, PA 19104, USA

3 University of Toronto, 27 King's College Circle, Toronto, ON M5 S 3G4, Canada

4 Mount Sinai Hospital, 600 University Avenue Toronto, ON M5G 1X5, Canada

5 Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA

6 Karolinska Institute, SE-171 77 Stockholm, Sweden and Karolinska Hospital, Huddinge 141 86 Stockholm, Sweden

7 Johnson & Johnson Pharmaceutical Services, LLC, 200 Great Valley Parkway, Malvern, PA 19355, USA

8 Elashoff Consulting, 11124 Yellow Leaf Way, Germantown, MD 20876, USA

9 Current address: Hoffman La-Roche, 340 Kingsland Street, Nutley, NJ 07110, USA

10 Current address: Pfizer Inc., 500 Arcola Road, Collegeville, PA 19426, USA

11 Current address: Buchanan Biotech Consulting, PO Box 1326, Mountain View, CA 94042, USA

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Arthritis Research & Therapy 2010, 12:R211  doi:10.1186/ar3188

Published: 17 November 2010

Abstract

Introduction

The goal of this study was to identify serum markers that are modulated by treatment with golimumab with or without methotrexate (MTX) and are associated with clinical response.

Methods

Sera were collected at weeks 0 and 4 from a total of 336 patients (training dataset, n = 100; test dataset, n = 236) from the GO-FORWARD study of patients with active rheumatoid arthritis despite MTX. Patients were randomly assigned to receive placebo plus MTX; golimumab, 100 mg plus placebo; golimumab, 50 mg plus MTX; or golimumab, 100 mg plus MTX. Subcutaneous injections were administered every 4 weeks. Samples were tested for select inflammatory, bone, and cartilage markers and for protein profiling using multianalyte profiles.

Results

Treatment with golimumab with or without MTX resulted in significant decreases in a variety of serum proteins at week 4 as compared with placebo plus MTX. The American College of Rheumatology (ACR) 20, ACR 50, and Disease Activity Score (DAS) 28 responders showed a distinct biomarker profile compared with nonresponding patients.

Conclusions

ACR 20 and ACR 50 responders among the golimumab/golimumab + MTX-treated patients had a distinct change from baseline to week 4 in serum protein profile as compared with nonresponders. Some of these changed markers were also associated with multiple clinical response measures and improvement in outcome measures in golimumab/golimumab + MTX-treated patients. Although the positive and negative predictive values of the panel of markers were modest, they were stronger than C-reactive protein alone in predicting clinical response to golimumab.

Trial registration

http://ClinicalTrials.gov webcite identification number: NCT00264550.