Women with rheumatoid arthritis (RA) who want to become pregnant are more likely to do so and do so faster if a treat-to-target approach is used than if it is not, Dutch researchers have found. 

More than three quarters of women became pregnant within 1 year with the treat-to-target approach vs just over half of women in a historical reference cohort, Cornelia Quaak, MD, and colleagues report ed in The Lancet Rheumatology.

The time to pregnancy was an average of 5 months faster comparing a treat-to-target that had been adapted for pregnant women vs no treat-to-target approach, with women becoming pregnant at a median of 91 days vs 251 days, respectively (P < .0001).

These data are “definitely enough to change guidelines,” senior author Radboud Dolhain, MD, PhD, told Medscape Medical News.

The findings show that striving for low disease activity, or preferably remission, before pregnancy is important, said Dolhain, who heads up the Department of Rheumatology at Erasmus University Medical Center Rotterdam, Netherlands, where the research was undertaken. 

“In our earlier studies, it took women a very long time to get pregnant, but it also meant that there’s a very long period of active disease,” Dolhain explained. High disease activity during pregnancy impacts the health of both the mother and child, he added, noting adverse pregnancy outcomes such as lower birthweights and earlier deliveries could be the result.

“This is the very first time that we've really clearly shown that [treat-to-target is] also associated with a shorter time to pregnancy,” said Dolhain, adding that it is “far better for the mother, for their RA, for their offspring, and they also get pregnant easier.”

Modernizing RA Treatment During Pregnancy 

The treat-to-target approach developed by Dolhain and his colleagues focuses on the use of conventional synthetic and biologic disease-modifying antirheumatic drugs (cs/bDMARDs) compatible with pregnancy while avoiding the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and high (> 7.5 mg/d) doses of prednisone. The aim is to achieve a disease activity in 28 joints (DAS28) below 2.6, with a DAS28 based on C-reactive protein of 2.6 or lower used to define clinical remission. 

Women and their partners are also given preconception counselling to help them understand the importance of health and lifestyle factors that could influence their fertility, including medication use and the timing of sexual intercourse. Women are also referred to a gynecologist for a preconception evaluation. 

The approach has already been shown in the Preconception Counseling in Active Rheumatoid Arthritis ( PreCARA) study to help more women achieve low disease activity or remission before pregnancy than a historical cohort of women from the Pregnancy-Induced Amelioration of Rheumatoid Arthritis (PARA) study who were treated according to the standards of the time and before treat-to-target was a possibility.

As an extension of this, Dolhain and team decided to look at whether the time to pregnancy was any different between the two cohorts of women who had been recruited at their institution between 2011 and 2023 for PreCARA and between 2002 and 2010 for PARA. Women were eligible for inclusion in these trials if they had inflammatory arthritis and were either planning to conceive or were already pregnant. 

PreCARA and PARA Patient Populations 

Individual patient data from women diagnosed with RA were used for the time-to-pregnancy study. In total, there were 215 women aged a mean of 32.4 years from PreCARA and 245 aged a mean of 31.8 years from PARA included. 

Disease activity before conception was significantly lower in PreCARA than in PARA, with respective DAS28 of 2.33 and 3.84. 

In terms of treatment for their RA, women in PreCARA were less likely to have been treated with NSAIDs (13% vs 24% for PARA) or doses of prednisone above 7.5 mg/d (11% vs 35%, respectively). Women in PreCARA were more likely to have been given a csDMARD such as sulfasalazine (69% vs 32%) or hydroxychloroquine (65% vs 6%) or a bDMARD, mainly a TNF inhibitor (53% vs 4%). The TNF inhibitors used were certolizumab pegol (40% vs 0%), etanercept (28% vs 89%), adalimumab (16% vs 11%), infliximab (14% vs 0%), and golimumab (2% vs 0%). 

‘Compelling Evidence’ for Proactive Approach 

Invited to comment on the research for The Lancet Rheumatology, Bonnie Bermas, MD, of the University of Texas Southwestern Medical Center in Dallas, noted that the time to pregnancy is an “important clinical question.” Bermas said the new PreCARA data provide “compelling evidence that proactive, treat-to-target disease management combined with specialized reproductive counselling can meaningfully improve reproductive outcomes.”

Bermas noted that the “intensive reproduction counseling” used in PreCARA but not in PARA could have also had an effect in itself and “represents an important unmeasured confounder.”

Speaking to Medscape Medical News, Bethan Goulden, MD, PhD, of University College London in the UK, said that the work adds “further weight to the idea that many disease-modifying therapies are not just ‘compatible’ with pregnancy and pregnancy planning to control maternal symptoms but that they are beneficial to fertility and pregnancy in their own right in individuals with inflammatory diseases like RA.”

Goulden, who was not involved in the research and is a dual-trained rheumatology and obstetric medicine specialist registrar and Arthritis UK clinical research fellow, noted that “many women planning pregnancy and the healthcare providers advising them will instinctively assume that fewer medications before and during pregnancy are better,” she said. 

The work “marks a broader evolution in the field of obstetric rheumatology, moving away from an infant risk/teratogenicity-focused mindset to an approach which acknowledges that effective treatment is itself part of good reproductive care,” Goulden said.

Ian Giles, MD, PhD, told Medscape Medical News separately that the research “adds further evidence of the importance of disease control leading up to pregnancy, to shorten the time to conception, and then we definitely want to continue that through the pregnancy to help improve outcomes.”

Giles, a professor of rheumatology at University College London and consultant rheumatologist University College London Hospitals NHS Foundation Trust, added: “What’s become clear in the last 10 years or so is that a great many medications can be used safely through pregnancy. It’s not the case that stopping the drugs and pregnancy makes everything better, as used to be taught for rheumatoid arthritis,” he said.

PreCARA and PARA were independently supported. Dolhain has received unrestricted research grants from the Dutch Arthritis Foundation and UCB, which together funded this study, and speaking fees from UCB, Novartis, and Eli Lilly. 

Bermas, Giles, and Goulden had no relevant conflicts of interest other than their specialist interest in managing pregnancy in RA. 

Sara Freeman is a freelance medical journalist based in London, England.