Prothrombotic biomarkers in patients with rheumatoid arthritis

The beneficial effect of IL-6 receptor blockade

Roberta Gualtierotti, Francesca Ingegnoli, Samantha Griffini, Elena Grovetti, Pier Luigi Meroni, Massimo Cugno

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objective The pro-inflammatory cytokine interleukin (IL)-6 is involved in the pathogenesis of both rheumatoid arthritis (RA) and cardiovascular events. We evaluated the correlation of prothrombotic biomarkers, in particular those of thrombin generation, with inflammatory and clinical parameters in RA patients treated with tocilizumab, an IL-6 receptor (IL-6R) inhibitor. Naïve and maintenance patients were compared. Methods We studied 15 RA patients undergoing tocilizumab infusions at a University Outpatient Clinic. Eight received tocilizumab for the first time and were evaluated at baseline. Seven were in maintenance therapy (9 to 77 months). All 15 patients were evaluated four weeks after the last administration of tocilizumab. At each time, we assessed disease activity score 28 (DAS28), erythrocyte sedimentation rate (ESR) and plasma levels of C-reactive protein (CRP), IL-6, soluble (s)IL-6R, tumour necrosis factor-alpha (TNF-alpha), prothrombin fragment F1+2 and fibrin fragment D-dimer. Forty healthy subjects served as basal controls. Results At baseline, RA patients showed a moderate-to-high disease activity and median ESR of 51 mm/1st hour (interquartile range 25-63). Plasma levels of CRP (p=0.0001), IL-6 (p=0.043), sIL-6R (p=0.003), TNF-alpha (p=0.0001), F1+2 (p=0.0001) and D-dimer (p=0.002) were higher than those of healthy controls. After four weeks we observed reduction of DAS28 (p=0.0001), ESR (p=0.0001), CRP (p=0.014), TNF-alpha (p=0.006), F1+2 (p=0.009) and D-dimer (p=0.04). No differences were observed between naïve and maintenance patients. Conclusion The reduction of prothrombotic biomarkers parallels the reduction of inflammatory parameters and clinical symptoms in RA patients treated with tocilizumab, both four weeks after the first administration and during maintenance therapy.

Original languageEnglish
Pages (from-to)451-458
Number of pages8
JournalClinical and Experimental Rheumatology
Volume34
Issue number3
Publication statusPublished - 2016

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Interleukin-6 Receptors
Rheumatoid Arthritis
Biomarkers
Blood Sedimentation
C-Reactive Protein
Interleukin-6
Tumor Necrosis Factor-alpha
Interleukins
Ambulatory Care Facilities
Thrombin
Healthy Volunteers
tocilizumab
Cytokines
Therapeutics

Keywords

  • Cardiovascular risk
  • Coagulation
  • IL-6
  • Inflammation
  • Prothrombotic biomarkers
  • Rheumatoid arthritis
  • Tocilizumab

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Prothrombotic biomarkers in patients with rheumatoid arthritis : The beneficial effect of IL-6 receptor blockade. / Gualtierotti, Roberta; Ingegnoli, Francesca; Griffini, Samantha; Grovetti, Elena; Meroni, Pier Luigi; Cugno, Massimo.

In: Clinical and Experimental Rheumatology, Vol. 34, No. 3, 2016, p. 451-458.

Research output: Contribution to journalArticle

Gualtierotti, Roberta ; Ingegnoli, Francesca ; Griffini, Samantha ; Grovetti, Elena ; Meroni, Pier Luigi ; Cugno, Massimo. / Prothrombotic biomarkers in patients with rheumatoid arthritis : The beneficial effect of IL-6 receptor blockade. In: Clinical and Experimental Rheumatology. 2016 ; Vol. 34, No. 3. pp. 451-458.
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abstract = "Objective The pro-inflammatory cytokine interleukin (IL)-6 is involved in the pathogenesis of both rheumatoid arthritis (RA) and cardiovascular events. We evaluated the correlation of prothrombotic biomarkers, in particular those of thrombin generation, with inflammatory and clinical parameters in RA patients treated with tocilizumab, an IL-6 receptor (IL-6R) inhibitor. Na{\"i}ve and maintenance patients were compared. Methods We studied 15 RA patients undergoing tocilizumab infusions at a University Outpatient Clinic. Eight received tocilizumab for the first time and were evaluated at baseline. Seven were in maintenance therapy (9 to 77 months). All 15 patients were evaluated four weeks after the last administration of tocilizumab. At each time, we assessed disease activity score 28 (DAS28), erythrocyte sedimentation rate (ESR) and plasma levels of C-reactive protein (CRP), IL-6, soluble (s)IL-6R, tumour necrosis factor-alpha (TNF-alpha), prothrombin fragment F1+2 and fibrin fragment D-dimer. Forty healthy subjects served as basal controls. Results At baseline, RA patients showed a moderate-to-high disease activity and median ESR of 51 mm/1st hour (interquartile range 25-63). Plasma levels of CRP (p=0.0001), IL-6 (p=0.043), sIL-6R (p=0.003), TNF-alpha (p=0.0001), F1+2 (p=0.0001) and D-dimer (p=0.002) were higher than those of healthy controls. After four weeks we observed reduction of DAS28 (p=0.0001), ESR (p=0.0001), CRP (p=0.014), TNF-alpha (p=0.006), F1+2 (p=0.009) and D-dimer (p=0.04). No differences were observed between na{\"i}ve and maintenance patients. Conclusion The reduction of prothrombotic biomarkers parallels the reduction of inflammatory parameters and clinical symptoms in RA patients treated with tocilizumab, both four weeks after the first administration and during maintenance therapy.",
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T2 - The beneficial effect of IL-6 receptor blockade

AU - Gualtierotti, Roberta

AU - Ingegnoli, Francesca

AU - Griffini, Samantha

AU - Grovetti, Elena

AU - Meroni, Pier Luigi

AU - Cugno, Massimo

PY - 2016

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N2 - Objective The pro-inflammatory cytokine interleukin (IL)-6 is involved in the pathogenesis of both rheumatoid arthritis (RA) and cardiovascular events. We evaluated the correlation of prothrombotic biomarkers, in particular those of thrombin generation, with inflammatory and clinical parameters in RA patients treated with tocilizumab, an IL-6 receptor (IL-6R) inhibitor. Naïve and maintenance patients were compared. Methods We studied 15 RA patients undergoing tocilizumab infusions at a University Outpatient Clinic. Eight received tocilizumab for the first time and were evaluated at baseline. Seven were in maintenance therapy (9 to 77 months). All 15 patients were evaluated four weeks after the last administration of tocilizumab. At each time, we assessed disease activity score 28 (DAS28), erythrocyte sedimentation rate (ESR) and plasma levels of C-reactive protein (CRP), IL-6, soluble (s)IL-6R, tumour necrosis factor-alpha (TNF-alpha), prothrombin fragment F1+2 and fibrin fragment D-dimer. Forty healthy subjects served as basal controls. Results At baseline, RA patients showed a moderate-to-high disease activity and median ESR of 51 mm/1st hour (interquartile range 25-63). Plasma levels of CRP (p=0.0001), IL-6 (p=0.043), sIL-6R (p=0.003), TNF-alpha (p=0.0001), F1+2 (p=0.0001) and D-dimer (p=0.002) were higher than those of healthy controls. After four weeks we observed reduction of DAS28 (p=0.0001), ESR (p=0.0001), CRP (p=0.014), TNF-alpha (p=0.006), F1+2 (p=0.009) and D-dimer (p=0.04). No differences were observed between naïve and maintenance patients. Conclusion The reduction of prothrombotic biomarkers parallels the reduction of inflammatory parameters and clinical symptoms in RA patients treated with tocilizumab, both four weeks after the first administration and during maintenance therapy.

AB - Objective The pro-inflammatory cytokine interleukin (IL)-6 is involved in the pathogenesis of both rheumatoid arthritis (RA) and cardiovascular events. We evaluated the correlation of prothrombotic biomarkers, in particular those of thrombin generation, with inflammatory and clinical parameters in RA patients treated with tocilizumab, an IL-6 receptor (IL-6R) inhibitor. Naïve and maintenance patients were compared. Methods We studied 15 RA patients undergoing tocilizumab infusions at a University Outpatient Clinic. Eight received tocilizumab for the first time and were evaluated at baseline. Seven were in maintenance therapy (9 to 77 months). All 15 patients were evaluated four weeks after the last administration of tocilizumab. At each time, we assessed disease activity score 28 (DAS28), erythrocyte sedimentation rate (ESR) and plasma levels of C-reactive protein (CRP), IL-6, soluble (s)IL-6R, tumour necrosis factor-alpha (TNF-alpha), prothrombin fragment F1+2 and fibrin fragment D-dimer. Forty healthy subjects served as basal controls. Results At baseline, RA patients showed a moderate-to-high disease activity and median ESR of 51 mm/1st hour (interquartile range 25-63). Plasma levels of CRP (p=0.0001), IL-6 (p=0.043), sIL-6R (p=0.003), TNF-alpha (p=0.0001), F1+2 (p=0.0001) and D-dimer (p=0.002) were higher than those of healthy controls. After four weeks we observed reduction of DAS28 (p=0.0001), ESR (p=0.0001), CRP (p=0.014), TNF-alpha (p=0.006), F1+2 (p=0.009) and D-dimer (p=0.04). No differences were observed between naïve and maintenance patients. Conclusion The reduction of prothrombotic biomarkers parallels the reduction of inflammatory parameters and clinical symptoms in RA patients treated with tocilizumab, both four weeks after the first administration and during maintenance therapy.

KW - Cardiovascular risk

KW - Coagulation

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KW - Inflammation

KW - Prothrombotic biomarkers

KW - Rheumatoid arthritis

KW - Tocilizumab

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