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

C. H. Brahe; C. Dehlendorff; M. Østergaard; J. S. Johansen; L. M. Ørnbjerg; K. Hørslev-Petersen; K. Stengaard-Pedersen; P. Junker; T. Ellingsen; H. Lindegaard; I. Hansen; T. Lottenburger; S. Jacobsen; A. G. Jurik; M. L. Hetland

doi:10.1080/03009742.2017.1376107

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

C. H. Brahe^*, C. Dehlendorff, M. Østergaard, J. S. Johansen, L. M. Ørnbjerg, K. Hørslev-Petersen, K. Stengaard-Pedersen, P. Junker, T. Ellingsen, H. Lindegaard, I. Hansen, T. Lottenburger, S. Jacobsen, A. G. Jurik, M. L. Hetland

^*Corresponding author for this work

Department of Clinical Medicine

1 Citation (Scopus)

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.

Original language	English
Journal	Scandinavian Journal of Rheumatology
Volume	47
Issue number	4
Pages (from-to)	259-269
Number of pages	11
ISSN	0300-9742
DOIs	https://doi.org/10.1080/03009742.2017.1376107
Publication status	Published - 2018

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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. (2018). 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. Scandinavian Journal of Rheumatology, 47(4), 259-269. https://doi.org/10.1080/03009742.2017.1376107

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. et al.

In: Scandinavian Journal of Rheumatology, Vol. 47, No. 4, 2018, p. 259-269.

Research output: Contribution to journal › Journal article › Research › peer-review

Brahe, CH, Dehlendorff, C, Østergaard, M , Johansen, JS, Ørnbjerg, LM, Hørslev-Petersen, K, Stengaard-Pedersen, K, Junker, P, Ellingsen, T, Lindegaard, H, Hansen, I, Lottenburger, T, Jacobsen, S, Jurik, AG & Hetland, ML 2018, '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', Scandinavian Journal of Rheumatology, vol. 47, no. 4, pp. 259-269. https://doi.org/10.1080/03009742.2017.1376107

Brahe CH, Dehlendorff C, Østergaard M , Johansen JS, Ørnbjerg LM, Hørslev-Petersen K et al. 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. Scandinavian Journal of Rheumatology. 2018;47(4):259-269. doi: 10.1080/03009742.2017.1376107

Brahe, C. H. ; Dehlendorff, C. ; Østergaard, M. et al. / 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. In: Scandinavian Journal of Rheumatology. 2018 ; Vol. 47, No. 4. pp. 259-269.

@article{3b359ee678764a39bf50965ec8ab3706,

title = "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",

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-na{\"i}ve patients with early RA (< 6 months{\textquoteright} 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{\textquoteright} 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{\textquoteright}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.",

author = "Brahe, {C. H.} and C. Dehlendorff and M. {\O}stergaard and Johansen, {J. S.} and {\O}rnbjerg, {L. M.} and K. H{\o}rslev-Petersen and K. Stengaard-Pedersen and P. Junker and T. Ellingsen and H. Lindegaard and I. Hansen and T. Lottenburger and S. Jacobsen and Jurik, {A. G.} and Hetland, {M. L.}",

year = "2018",

doi = "10.1080/03009742.2017.1376107",

language = "English",

volume = "47",

pages = "259--269",

journal = "Scandinavian Journal of Rheumatology",

issn = "0300-9742",

publisher = "Taylor & Francis",

number = "4",

}

TY - JOUR

T1 - 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

T2 - post-hoc explorative and validation studies based on the CIMESTRA and OPERA trials

AU - Brahe, C. H.

AU - Dehlendorff, C.

AU - Østergaard, M.

AU - Johansen, J. S.

AU - Ørnbjerg, L. M.

AU - Hørslev-Petersen, K.

AU - Stengaard-Pedersen, K.

AU - Junker, P.

AU - Ellingsen, T.

AU - Lindegaard, H.

AU - Hansen, I.

AU - Lottenburger, T.

AU - Jacobsen, S.

AU - Jurik, A. G.

AU - Hetland, M. L.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

U2 - 10.1080/03009742.2017.1376107

DO - 10.1080/03009742.2017.1376107

M3 - Journal article

C2 - 29336711

AN - SCOPUS:85041010893

SN - 0300-9742

VL - 47

SP - 259

EP - 269

JO - Scandinavian Journal of Rheumatology

JF - Scandinavian Journal of Rheumatology

IS - 4

ER -