BOSTON -- Current use of an intrauterine device (IUD) was associated with an important biomarker of future rheumatoid arthritis risk among women with a family history of the disease, according to a small study reported here.
In a cohort of women without current RA enrolled in the Studies of the Etiology of RA (SERA) project at the University of Colorado, three (12%) who were positive for antibodies to citrullinated protein antigens (ACPA), which often presage a clinical RA diagnosis, were currently using an IUD compared with 26 of 950 women who were ACPA negative (3%).
Action Points
- Note that these studies were published abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
"This was a statistically significant difference, with an odds ratio of 4.6," said , of the University of Colorado in Denver.
But there was no association between ACPA and previous IUD use or use of oral contraceptives.
"We don't yet know the cause of rheumatoid arthritis, but we do think that autoantibodies play a role in the development of disease because they are specific for RA and may be directly pathogenic for the joints," she said during a press conference at the
In studies of individuals during the preclinical phase of RA, a large proportion of those who ultimately develop the disease are ACPA positive several years before the onset of clinically apparent joint inflammation.
"So we have been very interested in what is involved in the development of these autoantibodies," she said.
Women are disproportionately affected by RA, developing the disease three times more commonly than men, and previous studies have suggested that female-specific factors may be associated with that difference, including contraceptive use and pregnancy.
However, most of those studies were in women who had already developed RA, and Demoruelle's group wanted to look at those factors during the preclinical period to see if influences could be detected at that point.
They enrolled 976 women in SERA, all of whom had a first-degree relative with RA so were at risk because of that history, but had no inflammatory arthritis based on clinical examination.
All participants had serum ELISA testing for the presence of ACPA, and filled out detailed questionnaires about contraceptive and pregnancy histories.
As to why use of an IUD might contribute to the development of RA, Demoruelle noted that she and her group are interested in further examining this relationship to see whether it might be a systemic or local effect.
"In RA, there are suggestions that the autoimmunity may initially occur at mucosal sites. Studies have looked at the effects of IUDs and found a local inflammatory response, so our hypothesis is that in women who are at risk for RA, this local inflammation could lead to systemic autoimmunity," she said.
There are caveats to the study, she noted. The population included individuals who all had first-degree relatives and therefore had a higher baseline risk for RA, so these findings may not necessarily be applicable to all women.
In addition, the study was cross-sectional, but her group plans to look at prospective data to see what happens over time to the autoimmunity and what happens following IUD removal.
Another limitation was that the questionnaire didn't consider the different types of IUDs.
Disclosures
The researchers disclosed no financial relationships.
Primary Source
American College of Rheumatology
Source Reference: Khatter S, et al "Contraceptive factors are associated with serum antibodies to citrullinated protein antigens in women at elevated risk for future rheumatoid arthritis" ACR 2014; Abstract 2921.