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Disease activity during pregnancy in patients with rheumatoid arthritis or spondyloarthritis: results from the multicentre prospective GR2 study

BMC Rheumatology volume 9, Article number: 30 (2025) Cite this article

Abstract

Background

Pregnancy may have a beneficial effect on disease activity in rheumatoid arthritis (RA) but the evidence is more conflicting in spondyloarthritis (SpA). The aim of this study was to analyse disease activity and relapse during pregnancy in women with RA and SpA.

Methods

Consecutive pregnant women with RA or SpA were enrolled in this French multicentre observational cohort from 2014 to 2022. Women who had at least two prenatal visits (including one in the first trimester) were included in the analysis. Disease relapse was defined as treatment intensification (initiation or switch of a DMARD) or increase in disease activity scores (DAS28-CRP for RA patients; ASDAS-CRP and/or BASDAI for SpA patients).

Results

Of the 124 pregnant women included, 53 had RA and 71 had SpA. A total of 18 (35%) RA and 44 (62%) SPA received a TNF inhibitor during pregnancy. At the group level, disease activity indexes remained stable in the 1st, 2nd and 3rd trimesters. Disease relapse during pregnancy occurred in 17 (32%) RA patients and 28 (39%) SpA patients, among whom 30 (24%) requiring a treatment intensification. In multivariable analysis, factors associated with disease relapse were nulliparity (odds ratio, OR: 6.5, 95%CI: 1.1 to 37.9) and a disease flare in the 12 months prior to conception (OR: 8.2, 95%CI: 1.6 to 42.7) for RA patients, and a history of bDMARD use (OR: 5.4, 95%CI: 1.1 to 27.3) for SpA patients.

Conclusion

Disease activity remained stable during pregnancy in women with RA and SpA but almost a quarter required major changes to their treatment.

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Introduction

Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are the most common chronic inflammatory rheumatisms affecting more women for RA, and with a balanced sex-ratio for SpA [1]. The prevalence of RA in women of reproductive age was estimated to be 0.2% in France [2].

Pregnancy is thought to have immunomodulatory effects to allow tolerance towards the semi-allogeneic foetus, leading to improvement in RA, but the exact mechanisms underlying spontaneous improvement remain to be elucidated [3]. Improvement in RA disease activity has been reported for years, but mainly from retrospective and old studies [4,5,6,7]. Decrease in disease activity during pregnancy has also been reported, to a lesser extent, in psoriatic arthritis. Results are more conflicting in axial SpA with some showing an increase in disease activity during the second trimester [8,9,10,11,12,13]. However, active disease during pregnancy has been described in 35–52% of patients with RA and in 60–80% of patients with axial SpA [5, 14].

Treatments to control disease activity have to be adapted before pregnancy: methotrexate, the cornerstone of RA treatment is contraindicated and only some antirheumatic drugs can be continued during pregnancy, mainly prednisone, sulfasalazine, hydroxychloroquine, and increasingly tumour necrosis factor (TNF) inhibitors [15]. In both diseases, discontinuation of TNF inhibitors in early pregnancy has been identified as a risk factor for disease flares [16]. The European League Against Rheumatism (EULAR) in 2016 and the French Club “Rhumatismes et Inflammations” in 2021 had recommended the continuation of TNF inhibitors during the first part of pregnancy and even certolizumab pegol and etanercept throughout pregnancy if necessary [17, 18]. However, data on disease activity in pregnant women with RA and SpA in the era of biologics are still scarce [7, 19, 20].

Using a recent nationwide prospective cohort of pregnant women with RA or SpA, this study aimed to assess disease activity during pregnancy and identify factors associated with disease relapse.

Methods

The GR2 study

The “Groupe de Recherche sur la Grossesse au cours des maladies Rares” (GR2) study (NCT02450396 registered on May 21, 2015 at https://www.clinicaltrials.gov/) is a French multicentre, prospective, observational study of pregnancies in women with rare autoimmune diseases (including systemic lupus erythematosus and antiphospholipid syndrome) and rheumatic diseases, including RA and SpA, conducted in France in 76 hospital centres. The methodology has been described previously [21,22,23]. The GR2 study is part of the European Network of Pregnancy Registries in Rheumatology (EuNeP), supported by the Foundation for Research in Rheumatology (FOREUM), and follows the EULAR recommendations for core data sets for pregnancy registries in rheumatology [24, 25]. Women with a rare and/or rheumatic disease are enrolled in the GR2 study in the preconception period or during pregnancy.

Investigators provided written information and obtained oral consent from each woman, as required by the French authorities. The local ethics committee (CPP Ile de France VI) approved the study protocol on August 29, 2012.

Patients

The GR2 study has been enrolling women with a diagnosis of RA or SpA according to their rheumatologist since December 2014. Patients could be enrolled in two ways: either in the preconception period or in the pregnancy period. In the preconception period, consecutive women with RA or SpA with a pregnancy wish (and who had discontinued their contraception) were followed yearly until pregnancy occurred or withdraw of the pregnancy wish or after five years of trying to conceive, whichever came first. In the pregnancy period, a visit was recommended for each trimester of pregnancy and 12 months post-partum.

For our study, we selected patients with RA or SpA who met international criteria (the 2010 ACR/EULAR criteria for RA, and the 2009 ASAS criteria for SpA) who had at least two visits during pregnancy, including one during the first trimester, and deliver before July 2022 (date of database extraction) [26, 27]. For women with more than one visit per trimester, only the first visit of each trimester was analysed.

Data collection

Demographic data, RA and SpA characteristics, rheumatic treatment history (number and type of conventional synthetic disease-modifying antirheumatic drugs [csDMARDs], biologic DMARDs [bDMARDs], received before conception), were collected at baseline (the first trimester of pregnancy).

Disease activity indexes were collected at each visit: disease activity score 28 joints CRP (DAS28-CRP) and DAS28-CRP-3 (excluding patient global assessment) [28] for RA, ankylosing spondylitis disease activity score CRP (ASDAS-CRP) and/or bath ankylosing spondylitis disease activity index (BASDAI) for SpA. Disease flare during the last 12 months before pregnancy was assessed by patient self-report for RA and SpA patients.

Disease remission was defined as a DAS28-CRP ≤ 2.6 for patients with RA, and an ASDAS-CRP ≤ 1.3 for patients with SpA.

Ongoing treatments of rheumatic disease, especially bDMARDs, were also recorded. For corticosteroids received during pregnancy, dose and duration were not available and were reported as a categorical variable (yes/no).

Definitions of relapse

For women with RA, disease relapse was defined as a treatment intensification (start or switch of a DMARD due to disease activity in the 2nd or 3rd trimester compared to baseline) and/or increase in DAS28-CRP (delta DAS28-CRP ≥ 0.6 and final DAS28-CRP > 3.2 or delta DAS28-CRP > 1.2) [29] For women with SpA, disease relapse was defined as a treatment intensification (start or switch of a DMARD due to disease activity in the 2nd or 3rd trimester compared to baseline) and/or delta ASDAS-CRP > 0.9 and/or, if ASDAS-CRP was not available, delta BASDAI > 2 [30, 31].

Switch of a DMARD for pregnancy reasons (i.e. switching from a not recommended molecule to a recommended molecule during pregnancy) was not considered as a treatment intensification.

Statistical analysis

Statistical analyses were performed using Stata software (version 15; StataCorp, College Station, TX, USA) for both pathologies separately (RA and SpA). All tests were two-sided, with an alpha level set at 5%. No imputation of missing data was performed. Categorical data are expressed as number of patients and percentages, and continuous data as mean ± standard deviation or median [25th; 75th percentiles] according to the statistical distribution. The percentage of relapse is presented with an exact binomial 95% confidence interval (CI). Longitudinal analyses of disease activity indexes (DAS28-CRP, ASDAS-CRP and BASDAI) were carried out by linear mixed models considering the trimester (first, second and third), the relapse (yes or no), and their interaction (trimester x relapse) as fixed effects, and the patient as a random effect. The factors associated with the relapse were studied by chi-squared test or Fisher’s exact test for categorical variables, and by Student’s t-test or Mann-Whitney test for quantitative ones. Adjusted analyses were also performed using multivariable logistic regressions (outcome: relapse), with covariates determined according to univariate results and clinical relevance. Due to the small sample size and to avoid collinearity, the number of covariates included in the models was limited (for RA: age at conception, nulliparity, and disease flare in the 12 months prior to conception; for SpA: age at conception, history of bDMARDs use, and HLA-B27 positive).

Results

Study population

A total of 124 pregnancies (including two twin pregnancies), occurring in 116 women, were analysed (Fig. 1). A comparison of included and excluded women has shown no differences in terms of age, disease duration, nulliparity and disease activity indices at the first trimester (data not shown). Of the124 included pregnancies, 53 occurred in patients with RA and 71 in patients with SpA. Of these, 75 (60.5%) had three visits (one per trimester) during pregnancy, and 49 (39.5%) had two visits. A preconception visit was available for 38 pregnancies. Patient’s characteristics and disease features of the study population are shown in Table 1.

Fig. 1
figure 1

Flowchart of the study. GR2: “Groupe de Recherche sur la Grossesse au cours des maladies Rares”; RA: rheumatoid arthritis; SpA: spondyloarthritis. *Date of data base extraction

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Table 1 Baseline characteristics of the patients with rheumatoid arthritis and spondyloarthritis
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RA patients

Among women with RA, 39/51 (76.5%) were rheumatoid factor positive, 37/52 (71.2%) were anti-citrullinated peptide antibody positive, and 24/52 (46.2%) had erosions. Overall, 42/53 (79.2%) of the RA patients had a history of corticosteroid use, 45 (84.9%) had ever received at least one csDMARD, 28 (52.8%) a bDMARD including 24 (45.3%) a TNF inhibitor. In the preconception period (12 months prior to conception), six women with RA discontinued methotrexate. A total of 18 (33.4%) women with RA received a TNF inhibitor at some point during pregnancy (15 [28.3%] in the first trimester, 16 [30.2%] in the second trimester and 15 [28.3%] in the third trimester). Certolizumab and etanercept were the most commonly used TNF inhibitors during pregnancy in RA patients. During pregnancy, one woman discontinued TNF inhibitor in the first trimester, two started a TNF inhibitor (1 certolizumab and 1 golimumab) during the second trimester, and one started a TNF inhibitor (certolizumab) during the third trimester.

Disease activity at baseline was low with a mean DAS28-CRP of 2.6 ± 1.3. A total of 23/40 (57.5%) RA were in remission at baseline according to DAS28-CRP. Average disease activity indexes remained stable in the 1st, 2nd and 3rd trimester of pregnancy (Fig. 2): for DAS28-CRP (2.6 ± 1.3, 2.3 ± 1.1, 2.5 ± 1.3 respectively, p = 0.48), and DAS28-CRP-3 (2.5 ± 1.1, 2.4 ± 0.9, 2.5 ± 1.1 respectively, p = 0.82). The evolution of disease activity assessed by the DAS28-CRP was not significantly different between relapsing and non-relapsing patients (Fig. 2).

Fig. 2
figure 2

Disease activity during pregnancy in women with rheumatoid arthritis (A) and spondyloarthritis (B, C). All “trimester x relapse” interactions, assessed by linear mixed models, are non-significant. The central mark is the median, the edges of the box are the 25th and 75th percentiles, the upper whisker is calculated as the maximum of (75th percentile + 1.5 × (75th percentile ─ 25th percentile)), and the lower whisker is calculated as the minimum of (25th percentile ─ 1.5 × (75th percentile ─ 25th percentile)). ASDAS-CRP: ankylosing spondylitis disease activity index using the C-reactive protein; BASDAI: bath ankylosing spondylitis disease activity index; DAS28-CRP: disease activity score in 28 joints using the C-reactive protein; T: trimester

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Disease relapse, as previously defined, occurred during pregnancy in 17 (32.1%, 95%CI: 19.9 to 46.3%) patients with RA. Among them, 10 required a treatment intensification. In univariate analysis, factors associated with disease relapse in patients with RA included a disease flare in the 12 months prior to conception and DAS28-CRP at baseline (Table 2). In multivariable analysis, nulliparity (OR: 6.5, 95%CI: 1.1 to 37.9) and a disease flare in the 12 months prior to conception (OR: 8.2, 95%CI: 1.6 to 42.7) still remained significantly associated with disease relapse (Table 3).

Table 2 Factors associated with relapse during pregnancy in RA and spa patients
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Table 3 Multivariable analysis of factors associated with relapse during pregnancy, in 43 patients with rheumatoid arthritis and 71 patients with spondyloarthritis
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SpA patients

Among women with SpA, 40 (56.3%) were HLA-B27 positive, most with axial manifestation (n = 36/70, 51.4%), and 44 (62.0%) had radiographic or MRI evidence of sacroiliitis. A total of 26 (36.6%) of had ever received a csDMARD, 57 (80.3%) a bDMARD and 55 (77.5%) a TNF inhibitor.

In the preconception period (12 months prior to conception), five women with SpA discontinued methotrexate. A total of 44 (62.0%) women with SpA received a TNF inhibitor at some point during pregnancy (38 [53.5%] in the first trimester, 31 [43.7%] in the second trimester and 27 [38.0%] in the third trimester), most commonly certolizumab. During pregnancy, 12 women stopped a TNF inhibitor in the first trimester: 5 certolizumab, 4 etanercept, 2 adalimumab and 1 infliximab. On the other hand, five women started a TNF inhibitor (3 certolizumab and 2 etanercept) during the second trimester, and one during the third trimester (certolizumab).

Disease activity at baseline was low with a mean ASDAS-CRP of 1.9 ± 1.2 and a mean BASDAI of 3.0 ± 2.1. At baseline, 14/37 (37.8%) were in remission according to ASDAS-CRP. Mean disease activity indexes remained stable in the 1st, 2nd and 3rd trimester of pregnancy according to ASDAS-CRP (1.9 ± 1.2, 2.0 ± 1.0, 1.7 ± 1.0 respectively, p = 0.60), and BASDAI (3.0 ± 2.1, 2.8 ± 2.0, 2.9 ± 2.1 respectively, p = 0.92).

Disease relapse, as previously defined, occurred during pregnancy in 28 (39.4%, 95%CI: 28.0 to 51.7%) patients with SpA. Of these, 20 required a treatment intensification. The evolution of disease activity indexes (ASDAS-CRP and BASDAI) was not significantly different between relapsing and non-relapsing patients (Fig. 2).

In univariate analysis, disease relapse was significantly associated with a history of bDMARD use (92.9% vs. 72.1%, p = 0.03) (Table 2). In multivariable analysis, the history of bDMARD use (OR: 5.4, 95%CI: 1.1 to 27.3) still remained significantly associated with disease relapse (Table 3).

Discussion

In this multicentre prospective study, we have reported that disease activity scores remained stable during pregnancy in women with RA and SpA.

Previous evidence on disease activity during pregnancy in patients with rheumatic disease was largely from retrospective studies until the 2000s. In 1999, Barrett et al. published the results of a large prospective national cohort of 141 pregnant women with RA showing a trend towards improvement in disability as assessed by the Health Assessment Questionnaire in the last trimester compared with preconception period, but this work lacked objective measures of disease activity [4]. In the PARA cohort of 84 pregnant women with RA, the beneficial effects of pregnancy on disease activity in the third trimester were more pronounced in those with moderate to high disease activity in the first trimester compared with those with low disease activity at baseline [5]. In 2019, Jethwa et al. performed a meta-analysis of 10 studies (ranging from 1983 to 2016) including 237 pregnant women with RA and reported an improvement (as assessed by various disease scoring systems) in 60% of the patients but 47% relapsed in the postpartum period [32]. In the more recent PARA study of 184 pregnancies in RA patients, disease activity remained stable during pregnancy and in the postpartum period. In women with SpA, there is less data on the effects of pregnancy on disease activity. In the Norwegian RevNatus registry, disease activity as assessed by the BASDAI was relatively stable with a slight increase during the second trimester compared with the post-partum period [10]. The GR2 study is a recent cohort (from 2014) mostly conducted in tertiary centres and contemporary with the increasing use of TNF inhibitors during pregnancy. Disease activity at baseline was relatively low in our cohort compared with previous report, and a large proportion of women with RA and SpA were in remission at the beginning of the pregnancy [28]. A significant proportion received a TNF inhibitor during pregnancy (35% of RA, 62% of SpA), in keeping with recent EULAR guidelines on treatment management during pregnancy [18]. This may explain the relative stability of disease activity during pregnancy in our patients.

However, we also observed that almost a third (32% of RA and 39% of SpA) of the women had a disease relapse during pregnancy. According to previous reports, a flare occurred in 29 to 38% of pregnant women with RA and in 25 to 80% of women with SpA [12, 16, 20, 33]. Flare is more complex than only an increase in disease activity scores [31, 34]. For this reason, we have adopted a pragmatic definition of disease relapse as a treatment intensification and/or an increase in disease activity scores. Several risk factors for disease relapse during pregnancy have been reported to date. Förger et al. reported that high levels of anti-CCP antibodies could be associated with high disease activity during pregnancy which was not observed neither by De man et al. or in our study [28, 35]. Discontinuation of TNF-alpha inhibitor early in the pregnancy may also be a risk factor for disease activity during the course of pregnancy [20]. Interstingly, in our study, a significant proportion of women, especially those with SpA, (SpA n = 12/38, RA n = 1/15) discontinued a TNF inhibitor during the first trimester of pregnancy. Several hypotheses could be put forward: the mother’s wish of not to expose the foetus to drugs, a medical decision regarding molecules, i.e. monoclonal antibodies such as adalimumab or infliximab.

Our study has some limitations. First, our small sample size which limits the power of our analysis, even though the GR2 remains the largest French cohort of pregnancies in rheumatic disease to date. Second, we used validated objective indices (DAS28-CRP, ASDAS-CRP and BASDAI) to assess disease activity but quality of life measures and patient-reported outcome were missing. Also, some parameters, such as the history of flare in the last 12 months, are patient-reported and could be affected by over- or underestimation. Thirdly, in the GR2 study, the daily glucocorticoid dose and the duration was unfortunately poorly reported, although it is a commonly used treatment in RA during pregnancy, leading to a possible underestimation of disease relapse. Four, we chose the first trimester of pregnancy as the baseline study time point because a large proportion of our population (more than two thirds) did not have a pre-pregnancy assessment of disease activity, which is known to be associated with disease activity during pregnancy. In addition, the relationship between disease activity during pregnancy and the postpartum period and the effect of breastfeeding on disease activity will be the subject of a separate paper. Indeed, the impact of the discontinuation of methotrexate in the preconception period was not evaluable because of lack of power.

Conclusion

Disease activity scores remained stable at mostly low levels during pregnancy in this contemporary cohort of women with RA and SpA but nearly a quarter of women required major changes to their treatment. Close monitoring of disease activity in pregnant women with RA or SpA is necessary, particularly for those with unstable rheumatism before conception for women with RA, and those who ever received bDMARDS for women with SpA.

Data availability

The datasets generated and/or analyzed during this study are available from the corresponding author upon reasonable request.

Abbreviations

ACR:

American College of Rheumatology

ASAS:

Assessment of SpondyloArthritis international Society

ASDAS-CRP:

Ankylosing Spondylitis Disease Activity Index using the C-reactive protein

BASDAI:

Bath Ankylosing Spondylitis Disease Activity Index

bDMARD:

biological Disease-Modifying Antirheumatic Drugs

CCTIRS:

Comité consultatif sur le traitement de l’information en matière de recherche dans le domaine de la santé

CI:

Confiance Interval

CNIL:

Commission nationale de l’informatique et des libertés

CPP:

Comité de Protection des Personnes

CRP:

C-reactive protein

csDMARD:

conventional Synthetic Disease-Modifying Antirheumatic Drugs

DAS28-CRP:

Disease Activity Score in 28 joints using the C-reactive protein

DMARD:

Disease-Modifying Antirheumatic Drugs

EULAR:

European League Against Rheumatism

EuNeP:

European Network of Pregnancy Registries in Rheumatology

FOREUM:

Foundation for Research in Rheumatology

GR2:

Groupe de Recherche sur la Grossesse au cours des maladies Rares

HLA-B27:

Human Leukocyte Antigen – B27

OR:

Odd Ratio

RA:

Rheumatoid Arthritis

SpA:

Spondyloarthritis

TNF:

Tumor Necrosis Factor

US:

United State

VAS:

Visual Analogue Scale

References

  1. Chimenti M-S, Alten R, D’Agostino M-A, et al. Sex-associated and gender-associated differences in the diagnosis and management of axial spondyloarthritis: addressing the unmet needs of female patients. RMD Open. 2021;7:e001681.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Pina Vegas L, Drouin J, Dray-Spira R, et al. Prevalence, mortality, and treatment of patients with rheumatoid arthritis: A cohort study of the French National health data system, 2010–2019. Joint Bone Spine. 2023;90:105460.

    Article  PubMed  Google Scholar 

  3. Bondt A, Hafkenscheid L, Falck D, et al. ACPA IgG galactosylation associates with disease activity in pregnant patients with rheumatoid arthritis. Ann Rheum Dis. 2018;77:1130–6.

    Article  CAS  PubMed  Google Scholar 

  4. Barrett JH, Brennan P, Fiddler M, et al. Does rheumatoid arthritis remit during pregnancy and relapse postpartum? Results from a nationwide study in the united Kingdom performed prospectively from late pregnancy. Arthritis Rheum. 1999;42:1219–27.

    Article  CAS  PubMed  Google Scholar 

  5. de Man YA, Dolhain RJEM, van de Geijn FE, et al. Disease activity of rheumatoid arthritis during pregnancy: results from a nationwide prospective study. Arthritis Rheum. 2008;59:1241–8.

    Article  PubMed  Google Scholar 

  6. Hazes JMW, Coulie PG, Geenen V, et al. Rheumatoid arthritis and pregnancy: evolution of disease activity and pathophysiological considerations for drug use. Rheumatology. 2011;50:1955–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Smeele HT, Röder E, Wintjes HM, et al. Modern treatment approach results in low disease activity in 90% of pregnant rheumatoid arthritis patients: the precara study. Ann Rheum Dis. 2021;80:859–64.

    Article  CAS  PubMed  Google Scholar 

  8. Ostensen M. The effect of pregnancy on ankylosing spondylitis, psoriatic arthritis, and juvenile rheumatoid arthritis. Am J Reprod Immunol. 1992;28:235–7.

    Article  CAS  PubMed  Google Scholar 

  9. Berman M, Zisman D, Wollman J, et al. The effect of pregnancy on disease activity in patients with psoriatic arthritis. J Rheumatol. 2018;45:1651–5.

    Article  PubMed  Google Scholar 

  10. Ursin K, Lydersen S, Skomsvoll JF, et al. Disease activity during and after pregnancy in women with axial spondyloarthritis: a prospective multicentre study. Rheumatology (Oxford). 2018;57:1064–71.

    Article  PubMed  Google Scholar 

  11. Maguire S, O’Dwyer T, Mockler D, et al. Pregnancy in axial spondyloarthropathy: A systematic review & meta-analysis. Semin Arthritis Rheum. 2020;50:1269–79.

    Article  PubMed  Google Scholar 

  12. Timur H, Tokmak A, Türkmen GG, et al. Pregnancy outcome in patients with ankylosing spondylitis. J Maternal-Fetal Neonatal Med. 2016;29:2469–73.

    Article  CAS  Google Scholar 

  13. Ostensen M. A prospective study of pregnant patients with rheumatoid arthritis and ankylosing spondylitis using validated clinical instruments. Ann Rheum Dis. 2004;63:1212–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Østensen M, Fuhrer L, Mathieu R, et al. A prospective study of pregnant patients with rheumatoid arthritis and ankylosing spondylitis using validated clinical instruments. Ann Rheum Dis. 2004;63:1212–7.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American college of rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Rheumatol. 2020;72:529–56.

    Article  PubMed  Google Scholar 

  16. Gerardi MC, Crisafulli F, García-Fernandez A, et al. Stopping bDMARDs at the beginning of pregnancy is associated with disease flares and preterm delivery in women with rheumatoid arthritis. Front Pharmacol. 2022;13:887462.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sellam J, Morel J, Tournadre A, et al. Practical management of patients on anti-TNF therapy - the CRI guidelines. Joint Bone Spine. 2021;88:105173.

    Article  PubMed  Google Scholar 

  18. Götestam Skorpen C, Hoeltzenbein M, Tincani A, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 2016;75:795–810.

    Article  PubMed  Google Scholar 

  19. Genest G, Spitzer KA, Laskin CA. Maternal and fetal outcomes in a cohort of patients exposed to tumor necrosis factor inhibitors throughout pregnancy. J Rheumatol. 2018;45:1109–15.

    Article  PubMed  Google Scholar 

  20. van den Brandt S, Zbinden A, Baeten D, et al. Risk factors for flare and treatment of disease flares during pregnancy in rheumatoid arthritis and axial spondyloarthritis patients. Arthritis Res Ther. 2017;19:64.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Larosa M, Le Guern V, Guettrot-Imbert G, et al. Evaluation of lupus anticoagulant, damage, and remission as predictors of pregnancy complications in systemic lupus erythematosus: the French GR2 study. Rheumatology (Oxford). 2022;61:3657–66.

    Article  CAS  PubMed  Google Scholar 

  22. Murarasu A, Guettrot-Imbert G, Le Guern V, et al. Characterisation of a high-risk profile for maternal thrombotic and severe haemorrhagic complications in pregnant women with antiphospholipid syndrome in France (GR2): a multicentre, prospective, observational study. Lancet Rheumatol. 2022;4:e842–52.

    Article  CAS  PubMed  Google Scholar 

  23. de Frémont GM, Costedoat-Chalumeau N, Lazaro E, et al. Pregnancy outcomes in women with primary Sjögren’s syndrome: an analysis of data from the multicentre, prospective, GR2 study. Lancet Rheumatol. 2023;5:e330–40.

    Article  PubMed  Google Scholar 

  24. Meissner Y, Strangfeld A, Costedoat-Chalumeau N, et al. European network of pregnancy registers in rheumatology (EuNeP)-an overview of procedures and data collection. Arthritis Res Ther. 2019;21:241.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Meissner Y, Fischer-Betz R, Andreoli L, et al. EULAR recommendations for a core data set for pregnancy registries in rheumatology. Ann Rheum Dis. 2021;80:49–56.

    Article  PubMed  Google Scholar 

  26. Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American college of rheumatology/european league against rheumatism collaborative initiative. Arthritis Rheum. 2010;62:2569–81.

    Article  PubMed  Google Scholar 

  27. Rudwaleit M, van der Heijde D, Landewé R, et al. The development of assessment of spondyloarthritis international society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis. 2009;68:777–83.

    Article  CAS  PubMed  Google Scholar 

  28. de Man YA, Hazes JMW, van de Geijn FE, et al. Measuring disease activity and functionality during pregnancy in patients with rheumatoid arthritis. Arthritis Rheum. 2007;57:716–22.

    Article  PubMed  Google Scholar 

  29. Bykerk VP, Bingham CO, Choy EH, et al. Identifying flares in rheumatoid arthritis: reliability and construct validation of the OMERACT RA flare core domain set. RMD Open. 2016;2:e000225.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Molto A, Gossec L, Meghnathi B, et al. An assessment in spondyloarthritis international society (ASAS)-endorsed definition of clinically important worsening in axial spondyloarthritis based on ASDAS. Ann Rheum Dis. 2018;77:124–7.

    Article  PubMed  Google Scholar 

  31. Godfrin-Valnet M, Puyraveau M, Prati C, et al. Flare in spondyloarthritis: thresholds of disease activity variations. Joint Bone Spine. 2015;82:192–5.

    Article  PubMed  Google Scholar 

  32. Jethwa H, Lam S, Smith C, et al. Does rheumatoid arthritis really improve during pregnancy?? A systematic review and metaanalysis. J Rheumatol. 2019;46:245–50.

    Article  PubMed  Google Scholar 

  33. High Risk of Flares during Pregnancy in Women with Rheumatoid Arthritis Who Discontinue Treatment with TNF Inhibitors at Conception. ACR Meeting, Abstracts. https://acrabstracts.org/abstract/high-risk-of-flares-during-pregnancy-in-women-with-rheumatoid-arthritis-who-discontinue-treatment-with-tnf-inhibitors-at-conception/ Accessed 1 Feb 2024.

  34. Bartlett SJ, Bykerk VP, Cooksey R, et al. Feasibility and domain validation of rheumatoid arthritis (RA) flare core domain set: report of the OMERACT 2014 RA flare group plenary. J Rhuematol. 2015;42:2185–9.

    Article  CAS  Google Scholar 

  35. Förger F, Vallbracht I, Helmke K, et al. Pregnancy mediated improvement of rheumatoid arthritis. Swiss Med Wkly. 2012;142:w13644.

    PubMed  Google Scholar 

Download references

Acknowledgements

None to declare.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Rheumatology Department, Université Clermont-Auvergne, CHU Clermont-Ferrand, 58 rue Montalembert, Clermont-Ferrand, 63000, France

    Marion Couderc & Martin Soubrier

  2. INSERM, Université Clermont-Auvergne, Clermont-Ferrand, France

    Marion Couderc

  3. Biostatistics Unit, DRCI, CHU Clermont-Ferrand, Clermont-Ferrand, France

    Céline Lambert

  4. Rheumatology Department, Hôpital Cochin, AP-HP, Paris, France

    Sabrina Hamroun & Anna Molto

  5. ECAMO Team, INSERM U-1153, Center of Research in Epidemiology and Statistics (CRESS), Université Paris-Cité, Paris, France

    Sabrina Hamroun, Nathalie Costedoat-Chalumeau & Anna Molto

  6. Department of Obstetrics, CHU Clermont-Ferrand, Clermont-Ferrand, France

    Denis Gallot

  7. Assistance Publique-Hôpitaux de Paris, Internal Medicine Department, Centre de Référence Maladies Auto-immunes et Systémiques Rares, Hôpital Cochin, Université de Paris, Paris, France

    Nathalie Costedoat-Chalumeau, Gaëlle Guettrot-Imbert & Veronique Le Guern

  8. INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique, Sorbonne Université, Paris, France

    Laure Gossec

  9. Assistance Publique-Hôpitaux de Paris, Rheumatology Department, Pitié-Salpêtrière hospital, Paris, France

    Laure Gossec

  10. Rheumatology Department, Centre de Référence des Maladie Autoimmunes et Systémiques Rares, Pellegrin Hospital, Centre Hospitalier Universitaire, Bordeaux, France

    Christophe Richez

  11. CNRS-UMR 5164, ImmunoConcept, Université de Bordeaux, Bordeaux, France

    Christophe Richez

Authors
  1. Marion Couderc
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  2. Céline Lambert
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  3. Sabrina Hamroun
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  4. Denis Gallot
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  5. Nathalie Costedoat-Chalumeau
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  6. Laure Gossec
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  7. Gaëlle Guettrot-Imbert
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  8. Veronique Le Guern
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  9. Christophe Richez
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  10. Martin Soubrier
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  11. Anna Molto
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Consortia

on behalf of the GR2 Study group

Contributions

M.C. and C.L. wrote the main manuscript, all the authors reviewed the manuscript.

Corresponding author

Correspondence to Marion Couderc.

Ethics declarations

Ethics approval and consent to participate

This study was conducted in compliance with the Declaration of Helsinki and its amendments. Informed consent was obtained from all the particpants, as required by the French authorities. The local ethics committee (CPP Ile de France VI) approved the study protocol on August 29, 2012.

Consent for publication

Not Applicable.

Competing interests

The authors declare no competing interests.

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Couderc, M., Lambert, C., Hamroun, S. et al. Disease activity during pregnancy in patients with rheumatoid arthritis or spondyloarthritis: results from the multicentre prospective GR2 study. BMC Rheumatol 9, 30 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s41927-025-00479-x

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  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s41927-025-00479-x

Keywords

BMC Rheumatology

ISSN: 2520-1026

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