Glycoprotein YKL-40: A potential biomarker of disease activity in rheumatoid arthritis during intensive treatment with csDMARDs and infliximab. Evidence from the randomised controlled NEO-RACo trial

PLoS One. 2017 Aug 25;12(8):e0183294. doi: 10.1371/journal.pone.0183294. eCollection 2017.

Abstract

Objective: YKL-40, a chitinase-like glycoprotein associated with inflammation and tissue remodeling, is produced by joint tissues and recognized as a candidate auto-antigen in rheumatoid arthritis (RA). In the present study, we investigated YKL-40 as a potential biomarker of disease activity in patients with early RA at baseline and during intensive treatment aiming for early remission.

Methods: Ninety-nine patients with early DMARD-naïve RA participated in the NEO-RACo study. For the first four weeks, the patients were treated with the combination of sulphasalazine, methotrexate, hydroxychloroquine and low dose prednisolone (FIN-RACo DMARD combination), and subsequently randomized to receive placebo or infliximab added on the treatment for further 22 weeks. Disease activity was evaluated using the 28-joint disease activity score and plasma YKL-40 concentrations were measured by immunoassay.

Results: At the baseline, plasma YKL-40 concentration was 57 ± 37 (mean ± SD) ng/ml. YKL-40 was significantly associated with the disease activity score, interleukin-6 and erythrocyte sedimentation rate both at the baseline and during the 26 weeks' treatment. The csDMARD combination decreased YKL-40 levels already during the first four weeks of treatment, and there was no further reduction when the tumour necrosis factor-α antagonist infliximab was added on the combination treatment.

Conclusions: High YKL-40 levels were found to be associated with disease activity in early DMARD-naïve RA and during intensive treat-to-target therapy. The present results suggest YKL-40 as a useful biomarker of disease activity in RA to be used to steer treatment towards remission.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / metabolism*
  • Biomarkers / metabolism*
  • Chitinase-3-Like Protein 1 / metabolism*
  • Female
  • Humans
  • Infliximab / therapeutic use*
  • Male
  • Middle Aged

Substances

  • Antirheumatic Agents
  • Biomarkers
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Infliximab

Grants and funding

This study was financially supported by the Competitive Research Funding of Tampere University Hospital (KV and EM), the Helsinki University Central Hospital Research Funds (ML-R) and Finska Läkaresällskapet (ML-R). At baseline an unrestricted grant was provided by Schering-Plough Finland, which was used for the purchase of infliximab. Schering-Plough Finland also provided support for investigator meetings. The funders did not have any role in the study design, data collection and analysis, preparation of the manuscript, or decision to publish.