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

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 identification number: NCT00264550.

Figure 1

Biomarker heatmaps for significant differences between baseline and week 4 for test and training datasets. Heatmaps representing biomarkers that were significantly different between baseline and week 4 for any of the treatment group for the training (a) and test (b) datasets. In the test dataset, only patients treated with golimumab were evaluated. Colors represent ranges of mean log₂ transformed biomarker levels at each time point (see legend for ranges).

Figure 2

Comparison of biomarkers significantly different between ACR responders and nonresponders for golimumab-treated patients. Mean ± SD comparison of biomarkers (log² transformed) that were significantly different between ACR 20 and ACR 50 responders and nonresponders for golimumab-treated patients in the Training and Test Subsets.