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

SUBMITTER: Visvanathan S

PROVIDER: S-EPMC3046519 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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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.

Visvanathan Sudha S Rahman Mahboob U MU Keystone Edward E Genovese Mark M Klareskog Lars L Hsia Elizabeth E Mack Michael M Buchanan Jacqui J Elashoff Michael M Wagner Carrie C

Arthritis research & therapy 20101117 6

<h4>Introduction</h4>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.<h4>Methods</h4>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 p ...[more]

PMID: 21083889

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Project description:ObjectiveReport on radiographic effects and maintenance of clinical benefit with intravenous golimumab 2 mg/kg+methotrexate (MTX) for up to week (wk) 52 in active rheumatoid arthritis (RA).MethodsPatients (n=592) with active RA (?6/66 swollen, ?6/68 tender joints, C reactive protein (CRP) ?1.0 mg/dL and positive for rheumatoid factor and/or anticyclic citrullinated protein antibody at screening) despite MTX ?3 months (stable dose of 15-25 mg/week for ?4 weeks) participated in this multicentre, international, randomised, double blind, placebo controlled, phase 3 study. Patients were randomised (2:1) to receive intravenous golimumab 2 mg/kg or placebo infusions at weeks 0 and 4 and then every 8 weeks; patients continued their stable MTX regimen. Placebo patients started golimumab 2 mg/kg at wk16 (early escape; <10% improvement in tender and swollen joints) or wk24 (crossover by design). Week 24 and wk52 radiographic (van der Heijde-Sharp (vdH-S) scores), clinical efficacy and safety data up to 1 year are reported here.ResultsSignificant and rapid clinical improvement was observed up to wk24 of intravenous golimumab therapy. Golimumab+MTX treated patients demonstrated less radiographic progression than placebo treated patients at wk24 (vdH-S score mean change 0.03 vs 1.09; p<0.001) and wk52 (0.13 vs 1.22; p=0.001). Among patients with ?20% improvement in the American College of Rheumatology response criteria or who achieved a 'good' or 'moderate' response according to the 28 joint Disease Activity Score employing CRP at wk24, approximately 80% maintained this response up until wk52. Through an average of 43.5 weeks of follow-up, 64.6% of patients receiving golimumab+MTX reported adverse events, most commonly non-serious infections.ConclusionsIn patients with active RA despite MTX, intravenous golimumab+MTX yielded significant inhibition of structural damage at wk24 and wk52, and sustained clinical improvement in signs and symptoms with no new safety signals up to 1 year.ClinicaltrialsgovNCT00973479, EudraCT 2008-006 064-11.

Project description:ObjectiveTo evaluate the safety and efficacy of golimumab through 5 years in adults with active rheumatoid arthritis (RA) who had not previously received methotrexate (MTX).MethodsIn the GO-BEFORE study, 637 MTX-naive adult patients with active RA were randomized (1:1:1:1) to placebo?+?MTX (group 1), golimumab 100 mg?+?placebo (group 2), golimumab 50 mg?+?MTX (group 3), or golimumab 100 mg?+?MTX (group 4). Inadequate responders in groups 1, 2, and 3 entered early escape at week 28 to golimumab 50 mg?+?MTX, golimumab 100 mg?+?MTX, or golimumab 100 mg?+?MTX, respectively; remaining patients in group 1 could cross over to golimumab 50 mg?+?MTX at week 52. Assessments included the American College of Rheumatology 20%/50%/70% improvement criteria (ACR20/50/70) response, the Disease Activity Score in 28 joints (DAS28) using C-reactive protein (CRP) level, and the modified Sharp/van der Heijde score (SHS). Efficacy was analyzed using an intent-to-treat (ITT) analysis. Pharmacokinetics and immunogenicity were evaluated at selected visits.ResultsA total of 422 patients completed golimumab treatment through week 256. At week 256, 72.8%, 54.6%, and 38.0% of all patients in the full ITT population (n?=?637) had an ACR20/50/70 response, respectively; 84.1% had a good or moderate DAS28-CRP response; and 72.7% had a clinically meaningful improvement in physical function. Radiographic progression was minimal in all treatment groups through week 256, and the overall mean change from baseline in SHS was 1.36. Serum trough golimumab concentrations were approximately dose proportional and maintained through week 256. Antibodies to golimumab occurred in 9.6% of patients through week 256. Infections were the most common type of adverse event (AE); 204 of 616 patients (33.1%) had ?1 serious AE.ConclusionClinical efficacy with golimumab treatment was maintained through week 256 of the GO-BEFORE trial of MTX-naive RA patients. No unexpected AEs occurred; safety results through 5 years are consistent with earlier reports.

Dataset Information

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.

Publications

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.

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