Objective
Even though systemic vasculitides (SVs) affect primarily patients over 50 years of age, they can occur among women of childbearing age. Preterm birth (PTB) and hypertensive disorders are ...frequent complications of pregnancy in SVs. This study aims to evaluate the risk of hypertensive disorders and PTB among pregnant women with SVs, and to identify associated risk factors.
Method
Using the French health insurance data warehouse, we conducted a nationwide cohort study including all pregnancies between 2013 and 2018 in women with SVs. Theses pregnancies were matched to pregnancies among women without SVs. We estimated risk of hypertensive disorders and PTB risk during pregnancy among women with SVs and investigated associated risk factors using a nested case‐control design.
Results
Among 3,155,723 pregnancies, we identified 646 pregnancies in women with SVs, matched to 3,230 controls. SVs were significantly associated with hypertensive disorders (odds ratio OR 1.7, 95% confidence interval 95% CI 1.3–2.2) and PTB (OR 1.8, 95% CI 1.4–2.3). Chronic renal failure before pregnancy, history of or treated arterial hypertension, the occurrence of vasculitides flare during pregnancy, and the subgroup of SVs were independently associated with the occurrence of hypertensive disorders. Maternal age at delivery, chronic renal failure before conception, and the occurrence of vasculitides flare during pregnancy were independently associated with the occurrence of PTB.
Conclusion
About one of seven pregnancies in women with SVs is associated with hypertensive disorders or preterm birth. The occurrence of vasculitides flare was associated with these complications. Our findings support the importance of prepregnancy counseling to ensure disease stability.
Primary Sjögren syndrome (pSS) is an autoimmune disorder characterized by ocular and oral dryness or systemic manifestations.
To evaluate efficacy and harms of rituximab in adults with recent-onset ...or systemic pSS.
Randomized, placebo-controlled, parallel-group trial conducted between March 2008 and January 2011. Study personnel (except pharmacists), investigators, and patients were blinded to treatment group. (ClinicalTrials.gov: NCT00740948).
14 university hospitals in France.
120 patients with scores of 50 mm or greater on at least 2 of 4 visual analogue scales (VASs) (global disease, pain, fatigue, and dryness) and recent-onset (< 10 years) biologically active or systemic pSS.
Randomization (1:1 ratio) to rituximab (1 g at weeks 0 and 2) or placebo.
Primary end point was improvement of at least 30 mm in 2 of 4 VASs by week 24.
No significant difference between groups in the primary end point was found (difference, 1.0% 95% CI, -16.7% to 18.7%). The proportion of patients with at least 30-mm decreases in at least two of the four VAS scores was higher in the rituximab group at week 6 (22.4% vs. 9.1%; P = 0.036). An improvement of at least 30 mm in VAS fatigue score was more common with rituximab at weeks 6 (P < 0.001) and 16 (P = 0.012), and improvement in fatigue from baseline to week 24 was greater with rituximab. Adverse events were similar between groups except for a higher rate of infusion reactions with rituximab.
Low disease activity at baseline and a primary outcome that may have been insensitive to detect clinically important changes.
Rituximab did not alleviate symptoms or disease activity in patients with pSS at week 24, although it alleviated some symptoms at earlier time points.
Obesity has significant implications for the health of pregnant women. However, few studies have quantified its association with maternal mortality or examined the relevant underlying causes and the ...role of care, although this remains the most severe maternal outcome. Our objectives were to quantify the risk of maternal death by prepregnancy body mass index and to determine whether obesity affected the quality of care of the women who died.
This is a national population-based case-control study in France. Cases were 364 maternal deaths from the 2007-2012 National Confidential Enquiry. Controls were 14,681 parturients from the nationally representative 2010 perinatal survey. We studied the association between categories of prepregnancy BMI and maternal death by multivariable logistic regression, estimating adjusted odds ratios and 95% confidence intervals, overall and by specific causes of death. Individual case reviews assessed the quality of care provided to the women who died, by obesity status.
Compared with women with normal BMI, underweight women (<18.5 kg/m
) had an adjusted OR of death of 0.75 (95% CI, 0.42-1.33), overweight women (25-29.9 kg/m
) 1.65 (95% CI, 1.24-2.19), women with class 1 obesity (30-34.9 kg/m
) 2.22 (95% CI, 1.55-3.19) and those with class 2-3 obesity (≥35 kg/m
) 3.40 (95% CI, 2.17-5.33). Analysis by cause showed significant excess risk of maternal death due to cardiovascular diseases, venous thromboembolism, hypertensive complications and stroke in women with obesity. Suboptimal care was as frequent among women with (35/62, 57%) as without obesity (136/244, 56%), but this inadequate management was directly related to obesity among 14/35 (40%) obese women with suboptimal care. Several opportunities for improvement were identified.
The risk of maternal death increases with BMI; it multiplied by 1.6 in overweight women and more than tripled in pregnant women with severe obesity. Training clinicians in the specificities of care for pregnant women with obesity could improve their outcomes.
Abstract
Objective
The detection of somatic mutations among the genes of myeloid cells in asymptomatic patients—defining clonal haematopoiesis of indeterminate potential (CHIP)—is associated with a ...predisposition to cardiovascular events (CVEs) in the general population. We aimed to determine whether CHIP was associated with CVEs in SLE patients.
Methods
The study is an ancillary study of the randomized, double-blind, placebo-controlled, multicentre PLUS trial conducted from June 2007 through August 2010 at 37 centres in France, involving 573 SLE patients. The search for somatic mutations by high-throughput sequencing of 53 genes involved in clonal haematopoiesis was performed on genomic DNA collected at PLUS inclusion. CHIP prevalence was assessed in SLE and in a retrospective cohort of 479 patients free of haematological malignancy. The primary outcome was an incident CVE in SLE.
Results
Screening for CHIP was performed in 438 SLE patients 38 (29–47) years, 91.8% female. Overall, 63 somatic mutations were identified in 47 patients, defining a CHIP prevalence of 10.7% in SLE. Most SLE patients (78.7%) carried a single mutation. Most variants (62.5%) were located in the DNMT3A gene. CHIP frequency was related to age and to age at SLE diagnosis, and was associated with a lower frequency of aPLs. CHIP occurred >20 years earlier (P < 0.00001) in SLE than in controls. The detection of CHIP at inclusion was not found to be associated with occurrence of CVEs during follow-up HR = 0.42 (0.06–3.21), P = 0.406.
Conclusion
The prevalence of CHIP is relatively high in SLE for a given age, but was not found to be associated with incident CVEs.
Trial registration
ClinicalTrials.gov, https://clinicaltrials.gov, NCT05146414.
Primary Sjögren syndrome is a systemic autoimmune disease characterized by mouth and eye dryness, pain, and fatigue. Hydroxychloroquine is the most frequently prescribed immunosuppressant for the ...syndrome. However, evidence regarding its efficacy is limited.
To evaluate the efficacy of hydroxychloroquine for the main symptoms of primary Sjögren syndrome: dryness, pain, and fatigue.
From April 2008 to May 2011, 120 patients with primary Sjögren syndrome according to American-European Consensus Group Criteria from 15 university hospitals in France were randomized in a double-blind, parallel-group, placebo-controlled trial. Participants were assessed at baseline, week 12, week 24 (primary outcome), and week 48. The last follow-up date for the last patient was May 15, 2012.
Patients were randomized (1:1) to receive hydroxychloroquine (400 mg/d) or placebo until week 24. All patients were prescribed hydroxychloroquine between weeks 24 and 48.
The primary end point was the proportion of patients with a 30% or greater reduction between weeks 0 and 24 in scores on 2 of 3 numeric analog scales (from 0 best to 10 worst) evaluating dryness, pain, and fatigue.
At 24 weeks, the proportion of patients meeting the primary end point was 17.9% (10/56) in the hydroxychloroquine group and 17.2% (11/64) in the placebo group (odds ratio, 1.01; 95% CI, 0.37-2.78; P = .98). Between weeks 0 and 24, the mean (SD) numeric analog scale score for dryness changed from 6.38 (2.14) to 5.85 (2.57) in the placebo group and 6.53 (1.97) to 6.22 (1.87) in the hydroxychloroquine group. The mean (SD) numeric analog scale score for pain changed from 4.92 (2.94) to 5.08 (2.48) in the placebo group and 5.09 (3.06) to 4.59 (2.90) in the hydroxychloroquine group. The mean (SD) numeric analog scale for fatigue changed from 6.26 (2.27) to 5.72 (2.38) in the placebo group and 6.00 (2.52) to 5.94 (2.40) in the hydroxychloroquine group. All but 1 patient in the hydroxychloroquine group had detectable blood levels of the drug. Hydroxychloroquine had no efficacy in patients with anti-SSA autoantibodies, high IgG levels, or systemic involvement. During the first 24 weeks, there were 2 serious adverse events in the hydroxychloroquine group and 3 in the placebo group; in the last 24 weeks, there were 3 serious adverse events in the hydroxychloroquine group and 4 in the placebo group.
Among patients with primary Sjögren syndrome, the use of hydroxychloroquine compared with placebo did not improve symptoms during 24 weeks of treatment. Further studies are needed to evaluate longer-term outcomes.
clinicaltrials.gov Identifier: NCT00632866.
To describe the characteristics of patients with Sjögren's disease (SjD) and inclusion-body myositis (IBM), and how they compare to SjD patients with other inflammatory myopathies (IM).
Patients were ...retrospectively recruited from 13 French centers and included if they met the ACR/EULAR criteria for SjD and for IM. They were categorized as SjD-IBM if sub-criteria for IBM were met, or as SjD-other IM if not.
SjD-IBM patients (n = 22) were mostly females (86%), with a median Q1; Q3 age of 54 38.5; 64 years at SjD diagnosis, and 62 46.5; 70 years at first IBM symptoms. Although most patients displayed glandular and immunological abnormalities, additional extra-glandular manifestations were uncommon, resulting in moderate disease activity at SjD diagnosis (ESSDAI 5.5 1; 7.8). Classic IBM features were frequent, such as progressive symptom onset (59%), asymmetrical (27%) and distal (32%) involvements, dysphagia (41%), low CPK (386.5 221.8; 670.5 UI/l) and CRP (3.0 3; 8.5 mg/l) levels. Immunosuppressants were reported as efficient in 55% of cases.Compared with SjD-IBM patients, SjD patients with other IM (n = 50) were significantly younger, displayed more frequent additional extra-glandular disease, higher ESSDAI score (11 3; 30), shorter delay between SjD diagnosis and myositis onset (0 -0.5; 26), more frequent CPK values over 1000 UI/l (36%), and less frequent classic IBM features.
IBM can occur in SjD patients, with muscle features reminiscent of classic sporadic IBM characteristics, but mostly affecting women. In SjD patients with muscle involvement, extra-glandular manifestations, high ESSDAI score, elevated CPK values, and shorter delay after SjD diagnosis plead against IBM.
Renal involvement is a rare event during primary SS (pSS). We aimed to describe the clinico-biological and histopathological characteristics of pSS-related nephropathy and its response to treatment.
...We conducted a French nationwide, retrospective, multicentre study including pSS patients fulfilling American-European Consensus Group criteria or enlarged American-European Consensus Group criteria, and with biopsy-proven renal involvement.
A total of 95 patients were included (median age 49 years). An estimated glomerular filtration rate (eGFR) of <60 ml/min was found in 82/95 patients (86.3%). Renal biopsy demonstrated tubulointerstitial nephritis (TIN) in 93 patients (97.9%), and frequent (75%) plasma cell infiltrates. Glomerular lesions were found in 22 patients (23.2%), mainly related to cryoglobulin. The presence of anti-SSA (76.8%) and anti-SSB (53.8%) antibodies was particularly frequent among patients with TIN and was associated with a worse renal prognosis. Eighty-one patients (85.3%) were treated, with CSs in 80 (98.8%) and immunosuppressive agents (mostly rituximab) in 21 cases (25.9%). Despite marked interstitial fibrosis at initial biopsy, kidney function improved significantly during the 12-month period following diagnosis (final eGFR 49.9 vs 39.8 ml/min/1.73 m 2 at baseline, P < 0.001). No proven benefit of immunosuppressive agents over steroid therapy alone was found in this study.
Renal involvement of pSS is mostly due to TIN with marked T, B and especially plasma cell infiltration. Renal dysfunction is usually isolated but can be severe. Use of CSs can improve the eGFR, but further studies are needed to define the best therapeutic strategy in this disease.
Objective: To investigate the safety and efficacy of rituximab (RTX) for systemic symptoms in patients with primary Sjögren’s syndrome (pSS), and changes in B cell biomarkers. Patients and methods: ...The records of 16 patients with pSS according to the American European consensus group criteria were reviewed retrospectively. Results: Patients, all women, had a median age of 58.5 (range 41–71) years and a disease duration of 9.5 (range 0–25) years. RTX was prescribed for lymphoma (n = 5), refractory pulmonary disease with polysynovitis (n = 2), severe polysynovitis (n = 2), mixed cryoglobulinaemia (n = 5), thrombocytopenia (n = 1) and mononeuritis multiplex (n = 1). The median follow-up duration was 14.5 (range 2–48) months. Three patients experienced adverse events, including one mild serum sickness-like reaction with the presence of human antichimeric antibodies. Efficacy of treatment was observed in 4 of 5 patients with lymphomas and in 9 of 11 patients with systemic involvement. Dryness was improved in only a minority of patients. Corticosteroid dose was reduced in 11 patients. RTX induced decreased rheumatoid factor, γ-globulin and β2-microglobulin levels, and the level of B cell activating factor of the tumour necrosis factor family (BAFF) increased concomitantly with B cell depletion. Five patients were re-treated, with good efficacy and tolerance, except for one with probable serum sickness-like reaction. Conclusion: This study shows good efficacy and fair tolerance of RTX for systemic features. In addition, RTX allows for a marked reduction in corticosteroid use. Except for BAFF, the level of which increases, serum B cell biomarker levels decrease after taking RTX. Controlled trials should be performed to confirm the efficacy of RTX in pSS.
Issues with pregnancy in systemic lupus Le Guern, Véronique; Guettrot-Imbert, Gaelle; Dupré, Anastasia ...
Joint, bone, spine : revue du rhumatisme,
12/2024, Volume:
91, Issue:
6
Journal Article
Peer reviewed
Open access
•The key to a successful pregnancy in a lupus patient is based on anticipation and comprehensive preconception counselling, which helps to optimise treatment and multidisciplinary ...management.•Reliable contraception should always be offered to avoid pregnancy during an active phase of the disease or during teratogenic treatment.•Although the prognosis of pregnancy in lupus patients has improved considerably over the last few decades, risks of maternal and fetal complications remain.•Hydroxychloroquine should be continued in lupus women during the preconception period and throughout pregnancy, reducing the risk of flare, and the recurrence of congenital heart block.•Anti-SSA and anti-SSB are associated with neonatal lupus syndrome, the most severe manifestation of which is congenital heart block.
Systemic lupus erythematosus is a disease that affects a large number of young women of childbearing age. Today, pregnancy is considered safe in almost all women with lupus, especially when the disease is under control. However, pregnancies in this population have a higher risk of maternal complications than in the general population. It is therefore important to plan pregnancies as effectively as possible, using effective contraception and pre-pregnancy counselling. In fact, effective, well-tolerated contraception is essential for patients for whom pregnancy cannot be safely envisaged, particularly in the setting of teratogenic treatment or significant disease activity. Preconception counselling is essential and helps to anticipate several aspects of a future pregnancy. Several recent prospective studies have clearly identified risk factors for obstetric complications and disease flare. High level of lupus activity, low complement, primigravida and a history of lupus nephritis are predictive factors of disease flare when antiphospholipid syndrome or antiphospholipid antibodies (specifically for lupus anticoagulant), damage, activity of lupus are predictive for obstetric events. Appropriate therapeutic management is essential, based primarily on the continuation of hydroxychloroquine, although some recent warnings about its use in pregnancy have been discussed controversially. Corticosteroid therapy can be continued at the lowest possible dose, as can certain immunosuppressive drugs. In the case of a history of lupus nephritis, low-dose aspirin is also prescribed. Although still exceptional, the risk of neonatal lupus is also higher, in patients with anti-SSA and anti-SSB antibodies. The aim of this review is to summarise the risk factors for adverse obstetric outcomes and to improve medical and obstetric management in this population of pregnant women with lupus.
Abstract The use of the conventional APS treatment (the combination of low-dose aspirin and LMWH) dramatically improved the obstetrical prognosis in primary obstetrical APS (OAPS). The persistence of ...adverse pregnancy outcome raises the need to find other drugs to improve obstetrical outcome. Hydroxychloroquine is widely used in patients with various autoimmune diseases, particularly SLE. Antimalarials have many anti-inflammatory, anti-aggregant and immune-regulatory properties: they inhibit phospholipase activity, stabilize lysosomal membranes, block the production of several pro-inflammatory cytokines and, in addition, impair complement-dependent antigen–antibody reactions. There is ample evidence of protective effects of hydroxychloroquine in OAPS similar to the situation in SLE arising from in vitro studies of pathophysiological working mechanism of hydroxychloroquine. However, the clinical data on the use of hydroxychloroquine in primary APS are lacking and prospective studies are necessary.
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