Low serum lipocalin-2 in pregnant women with systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) pregnancies are considered high-risk due to risk of disease flare and pregnancy complications. A more in-depth understanding of the immunological alterations in SLE patients during pregnancy and identification of predictive biomarkers may help to achieve stable disease and to avoid pregnancy complications. Lipocalin-2 (LCN2) has been implicated as a potential biomarker for rheumatic diseases and preeclampsia, but remains unexplored in SLE pregnancies. METHODS: We measured LCN2 levels in serum samples from SLE pregnancies (n=25) at seven different time points. Samples were taken preconception, in each trimester, at 6 weeks, 6 months and 12 months postpartum. Serum LCN2 levels were compared to samples from rheumatoid arthritis (RA) (n=27) and healthy (n=18) pregnancies at each time point using t-test, and for all time points using a linear mixed effects model. In addition, we investigated the association between LCN2 levels and disease activity, CRP, kidney function, BMI, treatment regimen and adverse pregnancy outcome for SLE and RA patients. RESULTS: We found significantly lower serum LCN2 levels throughout pregnancy in SLE patients with quiescent disease compared to RA and healthy pregnancies. We did not find an association between serum LCN2 and disease activity or adverse pregnancy outcome in SLE pregnancies. CONCLUSIONS: In a population of SLE women with low disease activity we have not found evidence that serum LCN2 levels predict disease activity or adverse pregnancy outcomes. Further studies are needed to elucidate a possible biological role of low LCN2 levels in SLE pregnancies.

Caesarean section in women with axial spondyloarthritis and psoriatic arthritis: a population-based study.

BACKGROUND: There is sparse documentation on pregnancy outcomes in women with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). Data on disease activity are often lacking, preventing the direct investigation of the effect of inflammation on pregnancy outcomes. A caesarean section (CS) implies a higher risk for complications than vaginal delivery. It delays mobilisation after birth necessary to counteract inflammatory pain and stiffness. OBJECTIVE: To explore a possible association of inflammatory active disease and CS rates in women with axSpA and PsA. METHODS: Data from the Medical Birth Registry of Norway (MBRN) were linked with data from RevNatus, a Norwegian nationwide observational register recruiting women with inflammatory rheumatic diseases. Singleton births in women with axSpA (n=312) and PsA (n=121) included in RevNatus 2010-2019 were cases. Singleton births, excluding mothers with rheumatic inflammatory diseases, registered in MBRN during the same period time (n=575 798) served as population controls. RESULTS: CS occurred more frequently in both axSpA (22.4%) and PsA (30.6%) groups compared with population controls (15.6%), with even higher frequencies in inflammatory active axSpA (23.7%) and PsA (33.3%) groups. Compared with population controls, women with axSpA had higher risk for elective CS (risk difference 4.4%, 95% CI 1.5% to 8.2%) but not emergency CS. Women with PsA had higher risk for emergency CS (risk difference 10.6%, 95% CI 4.4% to 18.7%) but not elective CS. CONCLUSION: Women with axSpA had higher risk for elective and women with PsA for emergency CS. Active disease amplified this risk.

Pregnancy and neonatal outcomes in women with axial spondyloarthritis: pooled data analysis from the European Network of Pregnancy Registries in Rheumatology (EuNeP).

OBJECTIVE: To investigate outcome and course of pregnancies in women with axial spondyloarthritis (axSpA) in a pooled data analysis of pregnancy registries in rheumatology. METHODS: Prospectively followed women with axSpA, fulfilling ASAS classification criteria and for whom a pregnancy outcome was reported, were eligible for the analysis. Anonymised data of four registries was pooled. Rates of adverse pregnancy outcomes were calculated. Systemic inflammation, disease activity and treatment patterns with tumour necrosis factor inhibitor (TNFi) before, during and after pregnancy were analysed. RESULTS: In a total of 332 pregnancies from 304 axSpA women, 98.8% of the pregnancies resulted in live birth. Mean maternal age was 31 years and disease duration 5 years. Most of these patients received pre-conception counselling (78.4%). Before pregnancy, 53% received TNFi treatment, 27.5% in first and 21.4% in third trimester. Pregnancy and neonatal outcomes were favourable with rates of 2.2% for pre-eclampsia, 4.9% for preterm birth, 3.1% for low birth weight and 9.5% for small for gestational age. Neonates were delivered by caesarean section in 27.7% of pregnancies, of which 47.4% were emergencies. Pooled mean CRP was 4 mg/L before conception peaking in the second trimester at 9.4 mg/L. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was below 4 at all time-points. CONCLUSIONS: Pooled rates of most outcomes were better than what had been reported in the literature and within expected rates of those reported for the general population. Pre-conception counselling, planned pregnancies and a tight management in expert centres applying a tailored treatment approach may have contributed to the favourable pregnancy outcomes.

Psoriatic Arthritis Disease Activity During and After Pregnancy: A Prospective Multicenter Study.

OBJECTIVE: To study disease activity in women with peripheral psoriatic arthritis (PsA) during and after pregnancy. Previous knowledge on this topic is sparse. METHODS: The study included 108 pregnancies in 103 women with PsA from a Norwegian nationwide register. Disease activity was assessed prospectively at 7 time points before, throughout, and after pregnancy with the 3-variable Disease Activity Score in 28 joints (DAS28) using C-reactive protein levels and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Scores assessed at each time point were analyzed in a linear mixed model. We did additional analyses with "tumor necrosis factor inhibitor (TNFi) in pregnancy" as a covariate. The same statistical method was used to study self-reported physical function, pain, and mental health. RESULTS: Approximately 75% of the women were in remission or had low disease activity during and after pregnancy according to the DAS28-CRP score. Although disease activity was altogether stable, we found that it decreased in pregnancy and increased within 6 months postpartum. Disease activity at 6 months postpartum was significantly higher than at 6 weeks postpartum (mean DAS28-CRP score 2.71 versus 2.45; P = 0.016). Women using TNFi in pregnancy had significantly lower disease activity than women not using TNFi (mean DAS28-CRP score at 6 months postpartum 2.22 versus 2.72; P = 0.043). BASDAI scores were also low and stable during pregnancy but significantly higher at 6 months postpartum than at 6 weeks postpartum (mean BASDAI score 3.69 versus 2.95; P = 0.013). CONCLUSION: Studying women with PsA, we found that disease activity was highest at 6 months postpartum but altogether low and stable in the period from planning pregnancy to 1 year after delivery. Women using TNFi in pregnancy had significantly lower disease activity.

No excess risks in offspring with paternal preconception exposure to disease-modifying antirheumatic drugs.

OBJECTIVE: To examine pregnancy outcomes in the partners of male patients with inflammatory joint disease who were or were not exposed to disease-modifying antirheumatic drugs (DMARDs) before conception compared with the outcomes in reference subjects from the general population. METHODS: Linkage of data from a longitudinal observational study of patients with inflammatory joint disease (the Norwegian Disease-Modifying Antirheumatic Drug [NOR-DMARD] registry study) and the Medical Birth Registry of Norway (MBRN) enabled a comparison of pregnancy outcomes in the partners of men with inflammatory joint disease. Outcomes of pregnancies in which the father was exposed to DMARDs within 12 weeks of conception and those in which the father was never exposed to DMARDs were analyzed separately and compared with the outcomes in reference subjects. Potential associations between DMARD exposure and adverse pregnancy outcomes were assessed by logistic regression analysis. RESULTS: A total of 1,796 men with inflammatory joint disease were associated with 2,777 births in the MBRN. In 110 of these births, the father had been exposed to DMARDs within 12 weeks before conception, and in 230 births the father had never been exposed to DMARDs before conception. The DMARDs (monotherapy or combination treatment) to which the fathers were exposed most frequently within 12 weeks of conception were methotrexate (n = 49), sulfasalazine (n = 17), and tumor necrosis factor inhibitors (n = 57). Neither adverse pregnancy outcomes nor occurrence of congenital malformations differed between patients and reference subjects in either group. CONCLUSION: Preconception paternal exposure to DMARDs was not associated with an increase in adverse pregnancy outcomes. Importantly, no increased risk of congenital malformations was observed.

Systemic lupus erythematosus and outcomes in first and subsequent births based on data from a national birth registry.

OBJECTIVE: To examine the associations between systemic lupus erythematosus (SLE) and outcomes in first and subsequent births. METHODS: Data from the Medical Birth Registry of Norway during the period December 1, 1998 to December 31, 2009 were used to assess maternal and perinatal outcomes in women diagnosed with SLE compared with the general population. Outcomes of first and subsequent births were analyzed separately. Associations between SLE and pregnancy outcomes were assessed in logistic regression analyses and are shown as adjusted odds ratios (aORs) after adjustment for maternal age, gestational age, smoking habits, and previous cesarean section (CS), when relevant. RESULTS: We analyzed 95 first and 145 subsequent births in patients and compared them with references. The risk of CS was two-fold higher in SLE patients in first and subsequent births. More newborns of patients had a birth weight <2,500 gm (aOR 5.00 [95 % confidence interval (95% CI) 3.02, 8.27] in first births and aOR 4.33 [95% CI 2.64, 7.10] in subsequent births). Additionally, preterm birth was more frequent among SLE patients (aOR 4.04 [95% CI 2.45, 6.56] in first births and aOR 3.13 [95% CI 1.97, 4.98] in subsequent births). Congenital malformations were more prevalent among children of patients than references (aOR 2.71 [95% CI 1.25, 5.86] in first births and aOR 3.13 [95% CI 1.69, 5.79] in subsequent births). Perinatal death was more frequent in first births among patients (aOR 7.34 [95% CI 2.69, 20.03]), but no difference was observed in subsequent births. CONCLUSION: Pregnancy complications were more frequent in SLE patients than references, and the greatest differences between groups were observed in first births.

Rheumatoid arthritis and outcomes in first and subsequent births based on data from a national birth registry.

OBJECTIVE: To examine associations between rheumatoid arthritis (RA) and pregnancy outcomes in first and subsequent births. DESIGN: Cohort study. SETTING: Study based on data registered in the Medical Birth Registry of Norway from the period 1 December 1998 to 31 December 2009. POPULATION: Singleton births in women recorded with RA (n = 1496) and reference deliveries from the general population (n = 625,642). METHODS: Outcomes of first and subsequent births were analyzed separately. First birth was defined as the first delivery of nulliparous women. Associations between RA and maternal and perinatal outcomes were assessed in logistic regression analyses and adjusted for maternal age at delivery, gestational age, smoking habits and for previous cesarean section when relevant. MAIN OUTCOME MEASURES: Maternal and perinatal outcomes. RESULTS: Vaginal bleeding was observed more often among women with RA both in first pregnancy [adjusted odds ratio (aOR) 1.8, 95% CI 1.3-2.4] and in subsequent pregnancies (aOR 1.4, 95% CI 1.1-1.9). Elective cesarean section was more common among women with RA both in the first birth (aOR 2.0, 95% CI 1.4-2.8) and in subsequent births (aOR 1.5, 95% CI 1.2-2.0). Preterm delivery was more frequent among women with RA than the reference population in first pregnancy (aOR 1.5, 95% CI 1.1-2.0) and in subsequent pregnancies (aOR 1.5, 95% CI 1.1-1.9). CONCLUSION: Complications and poor pregnancy outcomes were more often observed in women with RA and the greatest differences were observed in the first pregnancy.

Drug insight: Anti-tumor necrosis factor therapy for inflammatory arthropathies during reproduction, pregnancy and lactation.

Tumor necrosis factor (TNF) antagonists are widely used to reduce disease activity and joint damage, and to improve health-related quality of life in patients suffering from rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis. To date, no increased risk of embryotoxicity or teratogenicity, or adverse pregnancy outcome (such as birth defects, premature birth, and low birth weight) has been reported in patients with inflammatory arthropathies treated with anti-TNF therapy, compared with the general population. However, the available data are limited, and methotrexate, which is commonly used in combination with anti-TNF drugs, is teratogenic. Until more data are available, no firm conclusions can be reached regarding the safety of anti-TNF therapy in pregnancy. Nevertheless, in selected cases where there is high disease activity, anti-TNF therapy might be recommended, depending on the results of individual risk-benefit analyses. Fully informed consent from the mother is needed in such cases. Anti-TNF agents are not usually used during lactation, although the risk of toxicity is probably negligible.

[Clinical experience with TNF-alpha inhibitors in rheumatoid arthritis]. / Klinisk erfaring med TNF-alpha-hemmere ved revmatoid artritt.

BACKGROUND: Infliximab and etanercept, both tumour necrosis factor-alpha inhibitors, are proven to be effective in patients with rheumatoid arthritis in randomised controlled trials. MATERIAL AND METHODS: Patients with active rheumatoid arthritis were treated with infliximab (n = 29) or etanercept (n = 24) in clinical hospital practice. They were examined before and during treatment. All patients had tried at least one DMARD before. Details of disease activity were monitored by measuring tender and swollen joints, global and pain patient visual analogue scales, Disease Activity Index Score (DAS 28), the Modified Health Assessment Questionnaire, blood and urine samples, and adverse effects. The patients were monitored regularly for two years or until they stopped treatment. RESULTS: In the infliximab group we observed statistically significantly better values for all the registered variables after 6 weeks. At the other times of registration the variables were varying a lot; however, DAS 28 scores after baseline were all within the limits of moderate effect. In the etanercept group we observed statistically significantly better values for all the variables except for erythrocyte sedimentation rate after 6 weeks. At the other times of registration all the variables had significantly better values. Adverse effects were reported in 9 patients in the infliximab group and in 5 in the etanercept group, but no serious adverse effects were reported. 18 patients in the infliximab group (61%) and 10 in the etanercept group (42%) had stopped treatment within two years, either because of adverse effects or lack of effect. CONCLUSION: In this open study of patients with active rheumatoid arthritis, most experienced a rapid effect of infliximab, but a varying effect later on. In the etanercept group the patients experienced both a rapid and sustained effect among those who tolerated the medication. Compared to what several others have reported, a large number of patients stopped treatment; this may reflect limited experience.