NSAID exposure delays time-to-pregnancy in patients with spondyloarthritis: an analysis of the GR2 prospective cohort

Abstract

Background: The impact of disease activity and treatment on fertility outcomes in patients with spondyloarthritis (SpA) has been little explored. This study aimed to describe median time to pregnancy (TTP) in women with SpA and the factors influencing TTP in this population.

Methods: This prospective observational multicentre (63 centres) French cohort (GR2 study-NCT02450396) included consecutive women with a diagnosis of SpA (according to their rheumatologist) who wanted to become pregnant between 2015 and 2021. TTP (in months) was the main outcome criterion, prospectively calculated from the date of study inclusion to the date of conception. Data on demographics, disease characteristics, disease activity, severity and treatment were prospectively collected at inclusion and each year thereafter until pregnancy occurred. TTP and its associated factors were estimated by survival analysis (Shared Frailty Cox models), with a random centre effect and multiple imputation to address missing data.

Results: We analysed 88 women included before conception. Among them, 56 (63.6%) became pregnant during follow-up. Median TTP was 16.1 (95% CI (12.2 to 25.3)) months. Mean preconceptional Bath Ankylosing Spondylitis Disease Activity Index at inclusion was 2.9 (±SD 2.1). Patients were treated with TNF inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs and glucocorticoids in 61 (69.3%), 23 (26.1%), 12 (13.6%) and 8 (9.1%) cases, respectively. The multivariate model found a significant association between TTP and age (HR) (per year) 1.22 95% CI (1.08 to 1.40); p<0.001) and the use of NSAIDs during preconception (HR 3.01 95% CI (2.15 to 3.85); p=0.01).

Conclusion: Age and NSAID use during preconception were significantly associated with a longer TTP, after adjustment for other confounding factors. These findings warrant caution in the use of NSAIDs in SpA patients trying to conceive.

Keywords: Anti-Inflammatory Agents, Non-Steroidal; Axial Spondyloarthritis; Epidemiology; Spondyloarthritis.

Figure 1. Flow chart of SpA patients included in the preconception period. SpA, spondyloarthritis.

Figure 2. Cumulative pregnancy incidence in women with SpA with and without NSAID use in the preconceptional period. NSAIDs, non-steroidal anti-inflammatory drugs; SpA, spondyloarthritis.