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.

EULAR recommendations for a core data set for pregnancy registries in rheumatology.

BACKGROUND AND OBJECTIVE: There is an urgent need for robust data on the trajectories and outcomes of pregnancies in women with inflammatory rheumatic diseases (IRD). In particular when rare outcomes or rare diseases are to be investigated, collaborative approaches are required. However, joint data analyses are often limited by the heterogeneity of the different data sources.To facilitate future research collaboration, a European League Against Rheumatism (EULAR) Task Force defined a core data set with a minimum of items to be collected by pregnancy registries in rheumatology covering the period of pregnancy and the 28-day neonatal phase in women with any underlying IRD. METHODS: A stepwise process included a two-round Delphi survey and a face-to-face meeting to achieve consensus about relevant items. RESULTS: A total of 64 multidisciplinary stakeholders from 14 different countries participated in the two rounds of the Delphi process. During the following face-to-face meeting of the EULAR Task Force, consensus was reached on 51 main items covering 'maternal information', 'pregnancy' and 'treatment'. Generic instruments for assessment are recommended for every item. Furthermore, for the five most frequent IRDs rheumatoid arthritis, spondyloarthritis, juvenile idiopathic arthritis, systemic lupus erythematosus and other connective tissue diseases, disease-specific laboratory markers and disease activity measurements are proposed. CONCLUSION: This is the first consensus-based core data set for prospective pregnancy registries in rheumatology. Its purpose is to stimulate and facilitate multinational collaborations that aim to increase the knowledge about pregnancy course and safety of treatment in women with IRDs during pregnancy.

Risk for adverse pregnancy outcome in axial spondyloarthritis and rheumatoid arthritis: disease activity matters.

OBJECTIVE: To analyse pregnancy outcome and delivery mode in patients with RA and axial spondyloarthritis (axSpA) in relation to disease activity and anti-rheumatic drugs. METHODS: Patients with RA and axSpA were compared with age-matched healthy controls (HCs) with respect to pregnancy outcome and delivery mode. Disease activity (DAS28, ASDAS, CRP) and medication use of patients was assessed once at each trimester. ORs with 95% CI were calculated with univariate and multivariate regression models. RESULTS: We analysed 244 pregnancies, of which 96 occurred in patients with RA, 78 in patients with axSpA and 70 in HCs. The adjusted analysis showed that pregnant women with RA and axSpA had a higher risk of pregnancy complications (gestational diabetes, preeclampsia, infection, preterm premature rupture of membranes), small for gestational age infants and preterm deliveries (all P < 0.05). Active disease was a predictor for preterm delivery in both RA [odds ratio (OR) = 3.9, 95% CI: 1.25, 12.15] and axSpA (OR = 13.8, 95% CI: 1.33, 143.94). Regarding delivery mode, most patients had vaginal deliveries. However, women with RA revealed an increased risk of caesarean section compared with HC (P < 0.05), which was not seen in patients with axSpA. CONCLUSION: Our findings show that disease activity of RA and axSpA during pregnancy influences pregnancy outcome. To allow for successful pregnancy a treatment strategy that targets inactive disease beyond conception should be followed.

Rituximab and Canakinumab Use During Lactation: No Detectable Serum Levels in Breastfed Infants.

INTRODUCTION: In breastfeeding patients with chronic inflammatory rheumatic diseases, a postpartum flare may require the use of biologics. However, data on the safety of biologics during lactation are scarce, potentially impeding the decision-making process. CASE SERIES: We report two cases of women in whom treatment with a monoclonal IgG antibody (rituximab or canakinumab) was indicated during the lactation period. In both cases, breastfeeding was continued, and drug levels in the mother's serum, in serial breast milk samples and in the infant's serum were measured. Both rituximab and canakinumab showed minimal drug concentrations in breast milk and no detectable levels in the infants' sera. CONCLUSION: The lack of detectable levels of rituximab and canakinumab in the sera of breastfed infants reflects the poor oral bioavailability of these biologics and helps to promote their use in breastfeeding patients.

Risk factors for flare and treatment of disease flares during pregnancy in rheumatoid arthritis and axial spondyloarthritis patients.

BACKGROUND: During pregnancy, patients with rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) can experience active disease, which might be influenced by adjustment of treatment around conception. The aim of this study was to identify possible risk factors of disease flares during pregnancy and to evaluate the effect of treatment in pregnant patients experiencing a flare. METHODS: Pregnant patients with RA and axSpA were prospectively followed before, during, and after pregnancy. Disease activity and flares of disease activity were analyzed in regard to medication. RESULTS: Among 136 pregnant patients, disease flares during pregnancy occurred in 29% of patients with RA and in 25% of patients with axSpA. In both diseases, active disease and tumor necrosis factor inhibitor (TNFi) discontinuation in early pregnancy were identified as risk factors for disease flares during pregnancy. Of 75 patients with RA, 15 patients were on TNFi and discontinued the treatment at the time of the positive pregnancy test. After stopping TNFi, disease activity increased, which was reflected by peaking C-reactive protein levels at the first trimester. The relative risk of flare in patients with RA stopping TNFi was 3.33 (95% CI 1.8-6.1). Initiation of TNFi or glucocorticosteroid (GC) treatment in 60% of these patients resulted in disease improvement at the second and third trimesters. In comparison, patients with RA without TNFi in the preconception period, most of whom had used pregnancy-compatible antirheumatic drugs, showed mild and stable disease activity before and during pregnancy. Of 61 patients with axSpA, 24 patients were on TNFi and discontinued the treatment at the time of the positive pregnancy test. In patients with axSpA stopping TNFi, a disease aggravation at the second trimester could be observed. The relative risk of flare in this group was 3.08 (95% CI 1.2-7.9). In spite of initiated TNFi or GC treatment in 62.5% of these patients, disease activity remained elevated throughout pregnancy. Patients with axSpA without TNFi in the preconception period showed persistent high disease activity from prepregnancy until the postpartum period. CONCLUSIONS: On the basis of a risk-benefit analysis, to stabilize disease activity and to prevent a flare during pregnancy in patients with RA and axSpA, tailored medication including TNF inhibitors should be considered beyond conception.

[Ongoing breastfeeding with breast abscess]. / Aufrechterhaltung der Laktation bei Brustabszess.

Mastitis puerperalis can frequently be complicated by a breast abscess. Immediate diagnosis and treatment are crucial if breastfeeding is to be continued and for the prevention of further complications. Somatic and psychological interventions are of importance for recovery. Specialised nurses and midwives have an important impact on the promotion of well-being of affected mothers.

Certolizumab treatment during late pregnancy in patients with rheumatic diseases: Low drug levels in cord blood but possible risk for maternal infections. A case series of 13 patients.

OBJECTIVE: Due to reduction of immune-suppressive drugs, patients with rheumatic diseases can experience an increase in disease activity during pregnancy. In such cases, TNF-inhibitors may be prescribed. However, monoclonal antibodies with the Fc moiety are actively transported across the placenta, resulting in therapeutic drug levels in the newborn. As certolizumab (CZP) lacks the Fc moiety, it may bear a lower risk for the child. METHOD: We report a case series of thirteen patients (5 with rheumatoid arthritis and 8 with spondyloarthritis) treated with CZP during late pregnancy to control disease activity. RESULT: CZP measured in cord blood of eleven infants ranged between undetectable levels and 1µg/mL whereas the median CZP level of maternal plasma was 32.97µg/mL. Three women developed an infection during the third trimester, of whom one had a severe infection and one had an infection that resulted in a pre-term delivery. During the postpartum period, 6 patients remained on CZP while breastfeeding. CZP levels in the breast milk of two breastfeeding patients were undetectable. CONCLUSION: The lack of the active transplacental transfer of CZP gives the possibility to treat inflammatory arthritis during late gestation without potential harm to the newborn. However, in pregnant women treated with TNF-inhibitors and prednisone, attention should be given to the increased susceptibility to infections, which might cause prematurity. CZP treatment can be continued while breastfeeding.