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Changes in Iron Metabolism Induced by Anti-Interleukin-6 Receptor Monoclonal Antibody are Associated with an Increased Risk of Infection

Immune Response and Vascular Disease—CEDOC, Chronic Diseases Research Center, NOVA Medical School, 1150-082 Lisbon, Portugal
Systemic Immune-mediated Diseases Unit (UDIMS), Department of Medicine IV, Hospital Professor Doutor Fernando Fonseca, 2720-276 Amadora, Portugal
Author to whom correspondence should be addressed.
Pharmaceuticals 2019, 12(3), 100;
Received: 1 June 2019 / Revised: 20 June 2019 / Accepted: 25 June 2019 / Published: 28 June 2019
(This article belongs to the Special Issue Iron as Therapeutic Targets in Human Diseases)
(1) Background: Treatment of patients with rheumatoid arthritis (RA) with an anti-IL-6 receptor (anti-IL-6R) monoclonal antibody (tocilizumab) has been found to influence iron metabolism. The objective of the present study was to ascertain whether changes in iron metabolism induced by anti-IL-6R biologic therapy were independently associated with an increased infection risk. (2) Methods: A prospective longitudinal study of patients with RA treated with tocilizumab was conducted. RA patients treated with an antitumor necrosis factor α monoclonal antibody were also included as a control group. The primary outcome was occurrence of infection during the first 24 months of biologic therapy. (3) Results: A total of 15 patients were included, with a mean age of 51.0 ± 4,1 and 73.3% (n = 11) female. A multivariate survival regression model, adjusted for confounding factors, was fitted for each of the iron metabolism variables. Hazard ratios for being above the median of each parameter was considered. Transferrin saturation above the median value (>32.1%) was associated with a higher infection risk (HR 4.3; 95%CI 1.0–19.69; p = 0.05). Similarly, although non-significantly, higher serum iron was strongly associated with infection occurrence. (4) Conclusions: This study identified a probable association between infection risk and higher serum iron and transferrin saturation in patients with RA on anti-IL-6R biologic therapy. We suggest that both these parameters should be considered relevant contributing factors for infection occurrence in patients on anti-IL-6R therapy. View Full-Text
Keywords: iron; hepcidin; ferroportin; Interleukin-6; infection; rheumatoid arthritis iron; hepcidin; ferroportin; Interleukin-6; infection; rheumatoid arthritis
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Ribeiro, R.; Batista, F.; Seguro Paula, F.; Delgado Alves, J. Changes in Iron Metabolism Induced by Anti-Interleukin-6 Receptor Monoclonal Antibody are Associated with an Increased Risk of Infection. Pharmaceuticals 2019, 12, 100.

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