No association between recent antibiotic use and risk of rheumatoid arthritis: results from two prospective cohort studies

ABSTRACT

Background

Retrospective research partly characterizes the link between antibiotic use and rheumatoid arthritis (RA) development. This prospective cohort study may help reassess the association.

Research design and methods

We included 133,125 participants from the Nurses’ Health Study (NHS) and NHS II databases. Three groups were established: nonuse, short-term use (1–14 days), and middle- to long-term use (≥15 days) to explore the link. Cox regression model was chosen to evaluate the hazard ratios (HRs) for RA.

Results

Short-term antibiotic use was not associated with the subsequent risk of RA (adjusted HR = 0.88, 95% Confidence Interval [CI] 0.38–1.38) compared to the no antibiotic use group in the multivariable adjusted model. The age-stratified model showed no sufficient evidence of increased risk in participants with middle- to long-term antibiotic use (HR = 1.32, 95% CI 0.89–1.98). The effect further attenuated to null after controlling for confounding factors (adjusted HR = 1.06, 95% CI 0.42–1.71).

Conclusions

We found no evidence of an association between antibiotic use and RA risk. Our findings may reduce potential concerns about increased RA risk among antibiotic users.

KEYWORDS:

• Antibiotics
• rheumatoid arthritis
• cohort study
• confounding factors
• reverse causality

Acknowledgments

The authors would like to thank Prof. Jae Hee Kang and Prof. Francine Grodstein (Brigham and Women’s Hospital, Harvard Medical School, Boston, MA.) for their help in providing data.

Authors’ contributions

Benjie Zhou designed the study. Jinqiu Yuan collected the data for publication. Qiangsheng He analyzed the data. Yuxing Liu, Bin Xia, and Bo Li interpreted the data and drafted the manuscript. Benjie Zhou, Jinqiu Yuan, and Jeffrey A Sparks revised the manuscript. All authors read and approved the final manuscript.

Declaration of interest

The funders had no role in the design, conduct, or data interpretation of the study. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have received an honorarium from Expert Opinion on Drug Safety for their review work but have no other relevant financial relationships to disclose.

Data availability statement

Data may be obtained from a third party ([email protected]) and are not publicly available. Requests for access to data, questionnaires, and statistical code may be made by contacting the corresponding author at [email protected]. Questionnaire templates for this study are openly available in Nurses' Health Study at https://nurseshealthstudy.org/participants/questionnaires.

Ethics approval

The NHS and NHS II were approved by the Human Research Committee at Partners HealthCare, Boston, MA.

Consent to participate

Informed consent was obtained from all participants.

Geolocation information

The NHS, originally enrolled 121,700 female registered nurses from 11 U.S. states aged 30–55 years, and the NHS II included 116,430 younger female nurses aged 25–42 years from 14 U.S. states.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by the Natural Science Foundation of China; under Grant [numbers: 82003408, 82003524, 82074078]; Guangdong Provincial Key Laboratory of Digestive Cancer Research; under Grant [number 2021B1212040006]; the Startup Fund for the 100 Top Talents Program, Sun Yat-sen University; under Grant [number 392012]; and the National Institutes of Health; under Grant [numbers: L30 AR066953, K23 AR069688, R01 AR049880, R03 AR075886, K24 AR052403, UM1 CA186107, R01 CA49449, UM1 CA176726, R01 CA67262].