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IL-6 but Not TNFα Levels Are Associated With Time to Pregnancy in Female Rheumatoid Arthritis Patients With a Wish to Conceive

Fertility issues are common amongst women with rheumatoid arthritis (RA). Interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα), known key players in RA pathogenesis, have been associated with reproductive disorders. This study investigates the role of these cytokines in decreased fertility in...

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Autores principales: Bongenaar, Margot, Smeele, Hieronymus T. W., Lubberts, Erik, Dolhain, Radboud J. E. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758469/
https://www.ncbi.nlm.nih.gov/pubmed/33362560
http://dx.doi.org/10.3389/fphar.2020.604866
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author Bongenaar, Margot
Smeele, Hieronymus T. W.
Lubberts, Erik
Dolhain, Radboud J. E. M.
author_facet Bongenaar, Margot
Smeele, Hieronymus T. W.
Lubberts, Erik
Dolhain, Radboud J. E. M.
author_sort Bongenaar, Margot
collection PubMed
description Fertility issues are common amongst women with rheumatoid arthritis (RA). Interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα), known key players in RA pathogenesis, have been associated with reproductive disorders. This study investigates the role of these cytokines in decreased fertility in women with active RA. Preconception cytokine measurements of 61 patients from the PARA-cohort, a prospective study on RA and pregnancy, were studied in relation to time to pregnancy as a measure for fertility. IL-6 levels were higher in patients with a time to pregnancy longer than 1 year (p = 0.016). Survival analysis of patients stratified by high or low serum IL-6 levels, shows a prolonged time to pregnancy in the high IL-6 group (p = 0.045). Univariate cox regression analysis of IL-6 in relation to time to pregnancy as well as multivariate cox regression analysis correcting for age, disease activity, nulliparity, NSAID use and prednisone use were performed, with hazards ratios for log transformed IL-6 of 0.68 (95% CI: 0.51–0.93, p = 0.015) and 0.66 (95% CI: 0.43–0.99, p = 0.044), respectively. For TNFα, no association with time to pregnancy was found. This study shows that high IL-6, but not TNFα, is associated with decreased fertility in women with RA. This finding provides a rationale to therapeutically target the IL-6 pathway in the time period before pregnancy. More research in the form of large cohort studies on drug safety and the effect of bDMARDS on fertility is needed for implementation of treatment strategies directed at fertility issues in women with RA.
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spelling pubmed-77584692020-12-25 IL-6 but Not TNFα Levels Are Associated With Time to Pregnancy in Female Rheumatoid Arthritis Patients With a Wish to Conceive Bongenaar, Margot Smeele, Hieronymus T. W. Lubberts, Erik Dolhain, Radboud J. E. M. Front Pharmacol Brief Research Report Fertility issues are common amongst women with rheumatoid arthritis (RA). Interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα), known key players in RA pathogenesis, have been associated with reproductive disorders. This study investigates the role of these cytokines in decreased fertility in women with active RA. Preconception cytokine measurements of 61 patients from the PARA-cohort, a prospective study on RA and pregnancy, were studied in relation to time to pregnancy as a measure for fertility. IL-6 levels were higher in patients with a time to pregnancy longer than 1 year (p = 0.016). Survival analysis of patients stratified by high or low serum IL-6 levels, shows a prolonged time to pregnancy in the high IL-6 group (p = 0.045). Univariate cox regression analysis of IL-6 in relation to time to pregnancy as well as multivariate cox regression analysis correcting for age, disease activity, nulliparity, NSAID use and prednisone use were performed, with hazards ratios for log transformed IL-6 of 0.68 (95% CI: 0.51–0.93, p = 0.015) and 0.66 (95% CI: 0.43–0.99, p = 0.044), respectively. For TNFα, no association with time to pregnancy was found. This study shows that high IL-6, but not TNFα, is associated with decreased fertility in women with RA. This finding provides a rationale to therapeutically target the IL-6 pathway in the time period before pregnancy. More research in the form of large cohort studies on drug safety and the effect of bDMARDS on fertility is needed for implementation of treatment strategies directed at fertility issues in women with RA. Frontiers Media S.A. 2020-12-10 /pmc/articles/PMC7758469/ /pubmed/33362560 http://dx.doi.org/10.3389/fphar.2020.604866 Text en Copyright © 2020 Bongenaar, Smeele, Lubberts and Dolhain http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Brief Research Report
Bongenaar, Margot
Smeele, Hieronymus T. W.
Lubberts, Erik
Dolhain, Radboud J. E. M.
IL-6 but Not TNFα Levels Are Associated With Time to Pregnancy in Female Rheumatoid Arthritis Patients With a Wish to Conceive
title IL-6 but Not TNFα Levels Are Associated With Time to Pregnancy in Female Rheumatoid Arthritis Patients With a Wish to Conceive
title_full IL-6 but Not TNFα Levels Are Associated With Time to Pregnancy in Female Rheumatoid Arthritis Patients With a Wish to Conceive
title_fullStr IL-6 but Not TNFα Levels Are Associated With Time to Pregnancy in Female Rheumatoid Arthritis Patients With a Wish to Conceive
title_full_unstemmed IL-6 but Not TNFα Levels Are Associated With Time to Pregnancy in Female Rheumatoid Arthritis Patients With a Wish to Conceive
title_short IL-6 but Not TNFα Levels Are Associated With Time to Pregnancy in Female Rheumatoid Arthritis Patients With a Wish to Conceive
title_sort il-6 but not tnfα levels are associated with time to pregnancy in female rheumatoid arthritis patients with a wish to conceive
topic Brief Research Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758469/
https://www.ncbi.nlm.nih.gov/pubmed/33362560
http://dx.doi.org/10.3389/fphar.2020.604866
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