Rheumatoid arthritis (RA)

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By domain

Will pregnancy affect my RA? ●●●○moderate evidencestrong

de Man 2008 (PARA, verified primary text): among patients with at least moderate disease activity in the first trimester (n=52), at least 48% achieved a moderate EULAR response during pregnancy. Patients with low first-trimester disease activity (n=32) remained stable. Postpartum, 39% had at least a moderate flare by reversed EULAR criteria. This prospective study did not reproduce the older retrospective estimate of 75-90% improvement. PreCARA (Smeele 2021, primary text read): under a modified treat-to-target approach, LDA or remission rose from 75.4% pre-pregnancy to 90.4% in the third trimester, against 33.2% and 47.3% in the PARA comparator, with lower mean disease activity at every timepoint (p<0.001). No patient had a severe postpartum increase (PARA 5.7%, p=0.01); moderate increase 12.2% against 21.0% (p=0.18). Read as demonstrating attainability under structured care rather than as an effect estimate: observational, single tertiary centre, historic comparator, and PreCARA had longer disease duration but fewer erosions and lower preconception disease activity.^{[3, 4]}

Will RA affect the pregnancy? ●●●○moderate evidenceconditional

Generally favourable outcomes; active disease is associated with modestly increased preterm birth and small-for-gestational-age risk. Disease control is protective.^{[1, 3]}

Fertility ●●○○low evidenceconditional

Remission before conception is the actionable lever. In PreCARA, the 131 of 215 (61%) reaching DAS28-CRP 2.6 or lower had a median time to pregnancy of 65 days against 150 days in the 84 who did not (p=0.0054), with subfertility 19% against 30%; the remission subgroup approximates the general-population subfertility rate of about 18%. Overall, median time to pregnancy was 91 days (IQR 27 to 333) against 251 days (97 to 554) in the PARA historical cohort (p<0.0001), pregnancy within 1 year 77% against 58%, subfertility 23% against 42% (both p<0.0001), adjusted HR for occurrence of pregnancy 1.58 (95% CI 1.30 to 1.92). The approach: DMARDs intensified to DAS28 below 2.6 before conception, daily NSAIDs stopped, prednisone ideally 7.5 mg daily or less, pregnancy-compatible agents including TNF inhibitors, three-monthly preconception visits, and structured counselling on cycle, lifestyle and medication with gynaecology referral. Carries the design caveats on the clinician door only, by Dr. Mahendira's direction. Observational with a historical comparator: 26% enrolled already in the first trimester and 29% already trying, so preconception exposure is incompletely captured; PreCARA had longer disease duration but fewer erosions and lower preconception disease activity; BMI was not collected in PARA; confounding by indication is not excluded. The authors note that the counselling pathway and timed intercourse may themselves have contributed. No difference in time to pregnancy within PreCARA by TNF inhibitor or prednisone use. Maternal age and nulliparity remained independent predictors.^{[1, 5]}

Planning ahead ●●●○moderate evidencestrong

Discontinue methotrexate and leflunomide (with washout) pre-conception; transition to compatible DMARDs; aim to conceive in low disease activity.^{[1, 2]}

Medicines ●●●○moderate evidencestrong

Compatible options: hydroxychloroquine, sulfasalazine, azathioprine, TNF inhibitors (certolizumab convenient near term). Low-dose glucocorticoids for flares. Avoid methotrexate, leflunomide, JAK inhibitors.^{[1, 2]}

After birth ●●●○moderate evidenceconditional

Anticipate postpartum flare; pre-plan resumption of a breastfeeding-compatible regimen; most compatible DMARDs and TNF inhibitors suit lactation.^{[1, 2]}

Key points

Key numbers

• de Man 2008 (PARA): >=48% moderate EULAR response during pregnancy among those with >=moderate disease activity in the first trimester (n=52). Note the denominator is that subgroup, not all pregnancies.^[3]
• de Man 2008 (PARA): 39% had at least a moderate postpartum flare by reversed EULAR response criteria (n=84).^[3]

References

1. Sammaritano LR, et al. 2020 ACR Guideline for the Management of Reproductive Health in RMD. Arthritis Rheumatol. 2020;72(3):529-556. https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.41191
2. Ruegg L, et al. EULAR recommendations for antirheumatic drugs in reproduction, pregnancy, and lactation: 2024 update. Ann Rheum Dis. 2025;84(6):910-926. https://ard.eular.org/article/S0003-4967(25)00818-0/fulltext
3. de Man YA, et al. Disease activity of rheumatoid arthritis during pregnancy: results from a nationwide prospective study (PARA). Arthritis Rheum. 2008;59(9):1241-1248. https://pubmed.ncbi.nlm.nih.gov/18759316/
4. Smeele HTW, Roder E, Wintjes HM, Kranenburg-van Koppen LJC, Hazes JMW, Dolhain RJEM. Modern treatment approach results in low disease activity in 90% of pregnant rheumatoid arthritis patients: the PreCARA study. Ann Rheum Dis. 2021;80(7):859-864. doi:10.1136/annrheumdis-2020-219547 https://doi.org/10.1136/annrheumdis-2020-219547
5. Quaak CH, Roder E, Wintjes HM, van Steensel-Boon AJ, Mulders AGMGJ, Kranenburg-van Koppen LJC, Dolhain RJEM. Time to pregnancy in women with rheumatoid arthritis who want to conceive treated according to a treat-to-target approach: a comparison of an observational cohort with a historical reference cohort. Lancet Rheumatol. 2026;8(6):e461-e469. doi:10.1016/S2665-9913(26)00001-9 https://doi.org/10.1016/S2665-9913(26)00001-9