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Rapid beneficial effect of the IL-6 receptor blockade on insulin resistance and insulin sensitivity in non-diabetic patients with rheumatoid arthritis

1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12

 

  1. Rheumatology Division, Hospital Universitario de La Princesa, IIS-Princesa, Universidad Autónoma de Madrid (UAM), Madrid, Spain.
  2. Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain.
  3. Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain.
  4. Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain.
  5. Rheumatology Division, Hospital Universitario Txagorritxu, Vitoria, Araba, University of Basque Country, Araba, Spain.
  6. Rheumatology Division, Hospital Universitario de La Princesa, IIS-Princesa, Universidad Autónoma de Madrid (UAM), Madrid, Spain.
  7. Rheumatology Division, Hospital Universitario Sierrallana, Torrelavega, Cantabria, Spain.
  8. Rheumatology Division, Hospital Universitario de La Princesa, IIS-Princesa, Universidad Autónoma de Madrid (UAM), Madrid, Spain.
  9. Rheumatology Division, Hospital Universitario de La Princesa, IIS-Princesa, Universidad Autónoma de Madrid (UAM), Madrid, Spain.
  10. Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain.
  11. Division of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, Santander, and CIBER Epidemiología y Salud Pública (CIBERESP), Spain.
  12. Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Div., Hosp. Universitario Marqués de Valdecilla, IDIVAL and University of Cantabria, Santander; and Univ. of the Witwatersrand, South Africa.

CER11325
2019 Vol.37, N°3
PI 0465, PF 0473
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PMID: 30418124 [PubMed]

Received: 12/04/2018
Accepted : 23/07/2018
In Press: 07/11/2018
Published: 10/05/2019

Abstract

OBJECTIVES:
In patients with rheumatoid arthritis (RA), insulin resistance (IR), a component of the metabolic syndrome, is closely linked to the systemic inflammation induced by proinflammatory cytokines such as tumor necrosis factor-α and interleukin (IL)-6. In the present study, we aimed to assess if an intravenous administration of the anti-IL-6 receptor tocilizumab may yield a rapid improvement of IR in RA.
METHODS:
50 consecutive non-diabetic patients with RA refractory to methotrexate, undergoing periodic treatment with tocilizumab, were studied. Besides disease activity, serum insulin, insulin/glucose ratio, insulin resistance (HOMA-IR) and insulin sensitivity (QUICKI) indexes were assessed immediately before and 1 hour after the end of an intravenous administration of tocilizumab (given in saline solution over 60 minutes).
RESULTS:
When comparing baseline data (immediately before) and 1 hour after finishing tocilizumab administration, we observed a dramatic decrease of the serum insulin levels and insulin/glucose ratio. Also, a statistically significant reduction of IR (HOMA-IR: mean± standard deviation immediately before: 2.62±2.03 vs. 1.65±1.15 1 hour after the end of the infusion (p<0.01) and a statistically significant increase of insulin sensitivity (QUICKI immediately before 0.34±0.03 vs. 0.37±0.04 1 hour after the end of tocilizumab infusion (p<0.01) was observed.
CONCLUSIONS:
The intravenous administration of tocilizumab yields a rapid beneficial effect on IR and insulin sensitivity in non-diabetic RA patients. These findings support the potential beneficial effect of the IL-6 blockade on the mechanisms associated with the development of metabolic syndrome and cardiovascular disease in patients with RA.

Rheumatology Article