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 studyReportar como inadecuado




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 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Arthritis Research and Therapy

, 12:R211

First Online: 17 November 2010Revised: 18 October 2010Accepted: 17 November 2010

Abstract

IntroductionThe 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.

MethodsSera 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.

ResultsTreatment 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.

ConclusionsACR 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 registrationhttp:-ClinicalTrials.gov identification number: NCT00264550.

AbbreviationsACRAmerican College of Rheumatology

bFGFbasic fibroblast growth factor

CCPcyclic citrullinated peptide

CRPC-reactive protein

COMPcartilage oligomeric matrix protein

DASDisease Activity Score

ELISAenzyme-linked immunosrobent assay

ENAepithelium-derived neutrophil-activating protein

ESRerythrocyte sedimentation rate

FACIT-FFunctional Assessment of Chronic Illness Therapy -Fatigue

FDRfalse discovery rate

FGFfibroblast growth factor

ICAMintracellular adhesion molecule

ILinterleukin

MCPmonocyte chemotactic protein

MDCmonocyte-macrophage-derived chemokine or CCR-4

MCSmental component score

MIPmacrophage inflammatory protein

MMPmatrix metalloproteinase

MTXmethotrexate

NFnuclear factor

NPVnegative predictive value

P1NPN-terminal propeptide of type 1 procollagen

PAIplasminogen activator inhibitor

PCSphysical component score

PPVpositive predictive value

RArheumatoid arthritis

SF-3636-question Short Form Survey

SGOTserum glutamic oxaloacetic transaminase

SHBGsex hormone-binding globulin

TIMPtissue inhibitor of metalloproteinase

TNF-α tumor necrosis factor-α VEGFvascular endothelial growth factor.

Electronic supplementary materialThe online version of this article doi:10.1186-ar3188 contains supplementary material, which is available to authorized users.

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Autor: Sudha Visvanathan - Mahboob U Rahman - Edward Keystone - Mark Genovese - Lars Klareskog - Elizabeth Hsia - Michael Mack -

Fuente: https://link.springer.com/







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