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Circulating serum interleukin-6, serum chitinase-3-like protein-1, and plasma vascular endothelial growth factor are not predictive for remission and radiographic progression in patients with early rheumatoid arthritis: post-hoc explorative and validation studies based on the CIMESTRA and OPERA trials.
Brahe, C H; Dehlendorff, C; Østergaard, M; Johansen, J S; Ørnbjerg, L M; Hørslev-Petersen, K; Stengaard-Pedersen, K; Junker, P; Ellingsen, T; Lindegaard, H; Hansen, I; Lottenburger, T; Jacobsen, S; Jurik, A G; Hetland, M L.
Affiliation
  • Brahe CH; a Copenhagen Center for Arthritis Research (COPECARE), Centre for Rheumatology and Spine Diseases, Centre of Head and Orthopaedics , Rigshospitalet , Glostrup , Denmark.
  • Dehlendorff C; b Department of Clinical Medicine, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.
  • Østergaard M; c DANBIO Registry, Centre for Rheumatology and Spine Diseases, Centre of Head and Orthopaedics , Rigshospitalet , Glostrup , Denmark.
  • Johansen JS; d Danish Cancer Society Research Center , Danish Cancer Society , Copenhagen , Denmark.
  • Ørnbjerg LM; a Copenhagen Center for Arthritis Research (COPECARE), Centre for Rheumatology and Spine Diseases, Centre of Head and Orthopaedics , Rigshospitalet , Glostrup , Denmark.
  • Hørslev-Petersen K; b Department of Clinical Medicine, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.
  • Stengaard-Pedersen K; c DANBIO Registry, Centre for Rheumatology and Spine Diseases, Centre of Head and Orthopaedics , Rigshospitalet , Glostrup , Denmark.
  • Junker P; b Department of Clinical Medicine, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.
  • Ellingsen T; e Department of Medicine and Oncology, Herlev and Gentofte Hospital , University of Copenhagen , Herlev , Denmark.
  • Lindegaard H; a Copenhagen Center for Arthritis Research (COPECARE), Centre for Rheumatology and Spine Diseases, Centre of Head and Orthopaedics , Rigshospitalet , Glostrup , Denmark.
  • Hansen I; c DANBIO Registry, Centre for Rheumatology and Spine Diseases, Centre of Head and Orthopaedics , Rigshospitalet , Glostrup , Denmark.
  • Lottenburger T; f King Christian X Hospital for Rheumatic Diseases , South Jutland Hospital , Gråsten , Denmark.
  • Jacobsen S; g Department of Rheumatology , Aarhus University Hospital and lnstitute of Clinical Medicine, Aarhus University , Aarhus , Denmark.
  • Jurik AG; h Department of Rheumatology , Odense University Hospital , Odense , Denmark.
  • Hetland ML; i Diagnostic Centre , Silkeborg Regional Hospital , Silkeborg , Denmark.
Scand J Rheumatol ; 47(4): 259-269, 2018 07.
Article in En | MEDLINE | ID: mdl-29336711
ABSTRACT

OBJECTIVE:

To investigate serum interleukin-6 (IL-6), serum chitinase-3-like protein-1 (YKL-40), and plasma vascular endothelial growth factor (VEGF) as measures of disease activity and predictors of clinical remission and radiographic progression in two early rheumatoid arthritis (RA) randomized controlled trials (RCTs).

METHOD:

Treatment-naïve patients with early RA (< 6 months' duration) and active disease, participating in two investigator-initiated RCTs, were treated according to a predefined treat-to-target algorithm aiming at inflammatory control, using methotrexate (MTX) + cyclosporine versus MTX + placebo (CIMESTRA study, n = 150, 5 year follow-up) or MTX + adalimumab versus MTX + placebo (OPERA study, n = 180, 2 year follow-up). The 28-joint Disease Activity Score (DAS28) and conventional radiography [bilateral hands and feet at baseline, 2 years and 5 years (only CIMESTRA)] were obtained at baseline and during follow-up. Serum IL-6, serum YKL-40, and plasma VEGF were measured in baseline blood samples and during follow-up. Hypotheses regarding the biomarkers' relation with DAS28 and ability to predict clinical remission (DAS28 < 2.6) and radiographic progression (change in total Sharp van der Heijde score ≥ 2) were generated in CIMESTRA and validated in OPERA, by Spearman's correlation and logistic regression analyses.

RESULTS:

Baseline IL-6, YKL-40, and VEGF correlated significantly with DAS28 in CIMESTRA (r = 0.50, r = 0.36, r = 0.36, respectively, all p < 0.01) and these results were confirmed in OPERA patients (r = 0.52, p < 0.01; r = 0.18, p = 0.01; r = 0.23, p = 0.002, respectively). None of the biomarkers (absolute values or change) was predictive of clinical remission or radiographic progression at 2 or 5 years in either study.

CONCLUSION:

Serum IL-6, serum YKL-40, and plasma VEGF were significantly correlated with DAS28 at baseline, but did not have consistent predictive value for clinical remission or radiographic progression in two early RA RCTs.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Arthritis, Rheumatoid / Interleukin-6 / Vascular Endothelial Growth Factor A / Chitinase-3-Like Protein 1 Type of study: Clinical_trials / Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Female / Humans / Male / Middle aged Language: En Journal: Scand J Rheumatol Year: 2018 Document type: Article Affiliation country: Dinamarca

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Arthritis, Rheumatoid / Interleukin-6 / Vascular Endothelial Growth Factor A / Chitinase-3-Like Protein 1 Type of study: Clinical_trials / Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Female / Humans / Male / Middle aged Language: En Journal: Scand J Rheumatol Year: 2018 Document type: Article Affiliation country: Dinamarca
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