Researchers have described “a reassuring trend” of improving pregnancy outcomes over time in patients with axial spondyloarthritis (axSpA) alongside increased use of biological DMARDs, which could ultimately level the risk to that seen in the general population.
“If the current rate of improvement is maintained, women with axial spondyloarthritis treated in accordance with clinical guidelines might eventually not be at an increased risk of adverse pregnancy outcomes when treated in accordance with clinical practice guidelines,” the authors noted.
“This finding should be reassuring for both patients and practitioners, and could inform women with axial spondyloarthritis in their family planning.”
The register-based cohort study, undertaken in Sweden, matched 1,580 births in women with axSpA to 15,792 comparator births between April 1, 2007, and December 31, 2020.
Analysis revealed that women with axSpA were at higher risk compared to the general population of: preterm birth (6.3% versus 4.3%, respectively, adjusted risk ratio 1.43); pre-eclampsia (3.9% versus 2.8%, RR 1.44); elective caesarean delivery (14.9% vs 9.5%, RR 1.59), and serious infant infection (6.6% vs 5.0%, RR 1.29).
However, the increased risk of preterm birth, infant infection and caesarean delivery diminished by around 0.5 percentage points every year over the study period.
This was concurrent with an approximate 2% annual increase in use of TNF inhibitors during pregnancy, rising from under 20% in 2007 to around 40% in 2020, while use of NSAIDs, corticosteroids, and conventional systemic DMARDs during pregnancy were low during the study period.
Dr Antoni Chan, Consultant Rheumatologist and Physician, Clinical Lead in Rheumatology and axSpA at Royal Berkshire NHS Foundation Trust, told the limbic that the reduction in pregnancy complications seen in the trial was positive news that would improve the understanding of TNF inhibitor use during pregnancy.
“The reduction in infant infection with the increased use of TNF inhibitors should increase our confidence in using this treatment”, he said, noting that the study did not show direct causation between the use of TNF inhibitors and the improved pregnancy outcomes.
“Whether this [improved pregnancy outcomes] is due to the reduction of inflammation was not determined as there was missing data such as CRP and BASDAI. Better disease control and reduced inflammation levels prior to pregnancy with increased use of TNF inhibitors may have resulted in the improved pregnancy outcome,” he said.
“The improvement in pregnancy outcomes may have also been due to the reduction in the use of NSAIDs and prednisolone before and during pregnancy rather than from increased TNF inhibitor use”, he added.
Risk factors
With regard to potential risk factors, the study found no link between preterm birth and inflammation or disease activity in year preceding or during pregnancy, nor between type of treatment or presence of spondyloarthritis manifestations.
In fact, a significant effect modification was only seen with young maternal age and low education level, which were both associated with a higher risk of preterm birth in women with axSpA but not in the comparator arm.
“However, these specific factors are usually considered risk factors for preterm birth in the general population, and thus the lack of association in comparators in our study might be due to chance,” according to the paper.
Also of note, none of the potential risk factors assessed in the study were associated with a significantly increased risk of infant infection, while for pre-eclampsia a one unit increase in BASDAI was linked with a risk ratio of 1.50, though it was stressed that this should be interpreted with caution.
“Although it might be reasonable that higher disease activity confers a higher risk of adverse outcomes, BASDAI is based on subjective measures such as fatigue and pain, which might be related to symptoms of pre-eclampsia itself,” the investigators said.
Limitations of the study include a low proportion of pregnancies with disease activity data, as well as lack of information on the timing of treatments.
Nevertheless, the researchers said the findings indicate that despite increased use of powerful immunomodulatory treatments over the study period, the risk of adverse pregnancy outcomes in women with axial spondyloarthritis has significantly declined.
Dr Chan said study “will be welcome news to patients with axSpA and physicians who treat them”.
Looking forward, he noted that separating the pooled data into groups using ASAS Classification of radiographic and non-radiographic axial spondyloarthritis and by TNF inhibitor use in pregnancy would be informative. Further research was also needed to determine why the risk of pre-eclampsia did not improve compared to the other outcomes, he added.