FRI0145 High disease activity and preconceptional use of prednisone and non-steroidal anti-inflammatory drugs impair fertility in women with rheumatoid arthritis

Background

Fertility problems are more common in women with rheumatoid arthritis (RA) than in healthy women. Parity is reduced in female RA patients and the time to pregnancy (TTP) is increased.[1-3] Thus far, no studies have been performed to identify clinical factors associated with a prolonged TTP in female RA patients.

Objectives

to identify clinical factors associated with time to pregnancy in women diagnosed with RA

Methods

Patients were derived from the Pregnancy-induced Amelioration in Rheumatoid Arthritis (PARA) study, a nationwide prospective cohort study. Patients fulfilled the 1987 ACR criteria and were included in the study preconceptionally or during first trimester of pregnancy. Cox regression analysis was performed with age, parity, smoking, years since RA diagnosis, presence of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), disease activity (DAS28), use of methotrexate (MTX) in the past and use of non-steroidal anti-inflammatory drugs (NSAIDs), sulfasalazine or prednisone during the preconceptional period as explanatory variables.

Results

231 patients were available for analysis of whom 96 (42%) were subfertile (TTP longer than 12 months). Fifteen percent did not get pregnant. The mean age was 31.3±3.8 years. RF was positive in 73%, and ACPA in 65% of patients. The subfertile group differed significantly from the normally fertile group regarding age (31.9 years and 30.8 years respectively, p=0.037) and DAS28 (4.03 and 3.46 respectively, p<0.001). Use of NSAIDs (p=0.002) and prednisone (p=0.001) occurred more often in the subfertile group. Cox regression analysis with multiple variables showed strong evidence that age (p=0.034), nulliparity (p<0.001), DAS28 (p=0.010), preconceptional use of NSAIDs (p=0.008), and preconceptional use of prednisone (p=0.001) were associated with a longer TTP. Hazard ratios for occurrence of pregnancy were 0.96 (95%CI 0.92-0.99) per year of age, 0.54 (0.40-0.74) for nulliparity, 0.84 (0.73-0.96) per point increase in DAS28, 0.61 (0.42-0.88) for NSAID use and 0.58 (0.42-0.80) for prednisone use. Use of MTX in the past shortened the TTP (hazard ratio 1.43 (1.04-1.97) p=0.028). Smoking (p=0.486), time since RA diagnosis (p=0.844), RF positivity (p=0.274), ACPA positivity (p=0.273), and preconceptional sulfasalazine use (p=0.173) showed no significant association with TTP.

Conclusions

A prolonged time to pregnancy in female RA patients shows not only a significant association with age and parity, but also with increased disease activity scores, and preconceptional use of NSAIDs and prednisone. Use of MTX in the past seems to have a protective effect on fertility. Treatment strategies during the preconceptional period should aim at maximum suppression of RA disease activity, taking into account possible negative effects of NSAIDs and prednisone.

References

Clowse ME, et al. Effects of infertility, pregnancy loss, and patient concerns on family size of women with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Care Res (Hoboken). 2012 May;64(5):668-74. Jawaheer D, et al. Time to pregnancy among women with rheumatoid arthritis. Arthritis Rheum. 2011 Jun;63(6):1517-21. Del Junco DJ, et al. The relationship between rheumatoid arthritis and reproductive function. Br J Rheumatol. 1989;28 Suppl 1:33; discussion 42-5.

Acknowledgements

This study is funded by the Dutch Arthritis Association (Reumafonds).

Disclosure of Interest

None Declared