N-Terminal pro-Brain Natriuretic Peptide is a biomarker for cardiovascular damage in systemic lupus erythematous: a cross-sectional study.

OBJECTIVES: Prediction models based on traditional risk factors underestimate cardiovascular (CV) risk in systemic lupus erythematosus (SLE). In a large sample of unselected SLE patients, we investigated cross-sectional associations of NT-proBNP with cardiovascular damage (CVD). METHODS: Serum NT-proBNP was measured in SLE patients enrolled in the MUHC Lupus Clinic registry. Serum were collected between March 2022 and April 2023 at annual research visits. The primary outcome was CVD identified on the SLICC Damage Index. Factors associated with CVD and NT-proBNP levels were determined. RESULTS: Overall, 270 SLE patients (female 91%, median age 50.7 [1st quartile- 3rd quartile : 39.6-62.1] years) were analyzed for the primary outcome. Among them, 33 (12%) had CVD. The ROC curve for NT-proBNP demonstrated strong associations with CVD (AUC 0.78, 95% CI 0.69-0.87) with a threshold of 133 pg/ml providing the best discrimination for those with/without CVD. Hypertension (OR 3.3, 95% CI 1.2-9.0), dyslipidaemia (OR 3.6, 95% CI 1.3-9.6) and NT-proBNP > 133 pg/ml (OR 7.0, 95% CI, 2.6-19.1) were associated with CVD in the multivariable logistic regression model. Increased NT-proBNP levels were associated with age (OR 4.2, 95% CI 2.2-8.3), ever smoking (OR 1.9, 95% CI 1.0-3.5), reduced eGFR (4.1, 95% CI 1.3-13.1), prior pericarditis/pleuritis (OR 2.5, 95% CI 1.4-4.5) and aPL antibodies (OR 2.6, 95% CI 1.4-4.9). CONCLUSION: NT-proBNP is a biomarker for CV damage in SLE. The novel associations of NT-proBNP levels with prior pericarditis/pleuritis and aPL antibodies suggest new avenues for research to better understand what drives CV risk in SLE.

Association between chronic obstructive pulmonary disease, smoking, and interstitial lung disease onset in rheumatoid arthritis.

OBJECTIVES: In rheumatoid arthritis (RA), respiratory manifestations include chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). We assessed whether baseline COPD and smoking were associated with RA-ILD onset. METHODS: We identified new-onset ILD in incident RA subjects within the MarketScan Commercial Claims database, using physician and/or hospitalisation diagnostic codes. Smoking data (current, past, never) were available for a subset via a health questionnaire. Kaplan-Meier analyses assessed time to ILD onset, stratified by prior COPD and smoking. Multivariate Cox regression models were adjusted for age, sex, and (in the subset) smoking. Sensitivity analyses adjusted for past RA drugs. RESULTS: Among 373,940 new RA subjects, 6343 (1.7%) developed ILD (8.1 events per 1000 person-year, 95% CI 7.9, 8.3). ILD was more common among subjects with baseline COPD. Adjusting for age and sex, the hazard ratio (HR) between baseline COPD and incident ILD was 2.15, 95% CI 1.93, 2.39. We could not establish a clear relationship between current smoking and ILD; in the subset with smoking data, the HR point estimate for COPD was similar but the 95% CI was wider (due to fewer subjects) and included the null value. Adjusting for baseline RA drugs did not change results. CONCLUSIONS: Pre-existing COPD in incident RA subjects was associated with higher risk of future ILD. While a trend persisted after adjusting for smoking, we were limited by reduced sample size. Our study highlights the importance of ongoing assessments of potentially complicated relationships between smoking, COPD, and other factors in RA-associated ILD.

Clinical Significance of Raynaud Phenomenon in Systemic Lupus Erythematosus.

OBJECTIVE: There are limited reports of the clinical significance of Raynaud phenomenon (RP) in systemic lupus erythematosus (SLE), with some suggesting RP is associated with less severe lupus. Since most prior studies were small and/or focused on a specific race/ethnic demographic, it is unclear if those results are generalizable. We evaluated whether RP was associated with demographic and clinical factors in a large multiethnic SLE cohort. METHODS: We studied Montreal General Hospital SLE cohort patients who are followed with standardized annual assessments. We included patients with at least 1 visit across 2011-2018 and assessed demographic and clinical variables (using the 1997 American College of Rheumatology criteria and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) at their first visit. We present multivariate logistics regression analyses of cross-sectional associations between these variables and RP in SLE. RESULTS: Of 489 SLE patients, most were female (n = 445, 91%). Mean age at SLE diagnosis was 31.5 (standard deviation, 13.5) years, and 169 (34.6%) had RP. In our fully adjusted model, female sex (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.07-6.03), White race/ethnicity (OR, 1.85; 95% CI, 1.10-3.17), neurological/neuropsychiatric manifestations (OR, 1.98; 95% CI, 1.10-3.56), and anti-RNP antibodies (OR, 3.03; 95% CI, 1.73-5.38) were positively associated with RP, whereas hemolytic anemia and cellular casts were negatively associated. CONCLUSIONS/DISCUSSION: Over one third of our large multiethnic North American SLE cohort had RP. This study confirmed associations between RP and a specific SLE phenotype.

Induced abortions in women with systemic lupus erythematosus.

OBJECTIVES: To determine the rates of induced abortions in women with systemic lupus erythematosus (SLE) compared to women from the general population and assess disease-related predictors of induced abortion in women with SLE. METHODS: We identified women with SLE (15-45 years) and determined the number of induced abortions, using Quebec's administrative databases. We calculated the standardized incidence ratio (SIR) using general population rates. We also performed a nested-case control analysis to investigate predictors of induced abortions in SLE women (such as teratogenic immunosuppressive and corticosteroid exposures). RESULTS: Among 2508 women with SLE, we observed 293 induced abortions [incidence rate of 17.1 induced abortions per 1000 person-years (95% CI 15.2, 19.2)]. There was no clear difference in the number of induced abortions among women with SLE versus women from the general population (SIR 1.10; 95% CI 0.98, 1.24). In the multivariable analysis, we did not observe higher rates of induced abortions among women exposed to teratogenic immunosuppressives [rate ratio (RR) 0.37; 95% CI 0.13, 1.07] or using corticosteroids (RR 0.67; 95% CI 0.39, 1.16). CONCLUSION: Our findings suggest that women with SLE have a similar rate of induced abortions as compared to the general population. This raises some concerns as unplanned pregnancies in SLE women can lead to adverse maternal and fetal outcomes. Our results should prompt further research on family planning counselling in women with SLE.

Myositis in systemic lupus erythematosus.

OBJECTIVES: Myositis is an infrequent feature of SLE and may often be overlooked. We aimed to estimate the incidence of myositis in SLE, and to determine demographic and clinical factors associated with it. METHODS: Within our lupus cohort, we identified potential myositis cases using the SLICC Damage Index for muscle atrophy or weakness, the SLEDAI-2K item for myositis, and annually measured serum creatinine kinase. Cases were confirmed through chart review. We performed descriptive analyses of prevalent myositis cases as of January 2000. From that point onward, we studies patients without myositis to determine risk of incident myositis, using cohort analyses adjusted for demographic variables (age, sex, race/ethnicity). RESULTS: As of January 2000, there were 5 prevalent myositis cases in our SLE cohort. Among 560 SLE patients with a study visit from January 2000 onward, with no history of myositis at baseline, 5 new cases (4 females, 1 male) were identified over an average follow-up of 8.5 years (incidence 1.05 cases per 1000 person-years). There was a higher proportion of Caucasians in the non-myositis group versus myositis group, with a trend for fewer females in the myositis cases. Arthritis, Raynaud's phenomenon, and anti-Smith antibodies were common pre-existing features, occurring in all incident myositis cases. In Cox regression analyses adjusting for age, race/ethnicity and sex, non-Caucasian patients had a markedly increased risk of developing myositis. CONCLUSION: We found a low incidence of myositis in our SLE cohort. A cluster of variables, particularly non-Caucasian race/ethnicity, arthritis, Raynaud's phenomenon, and anti-Smith antibodies were associated with risk of developing myositis in SLE. These variables may aid clinicians in identifying SLE patients at highest risk for this important complication.

Use of combined hormonal contraceptives among women with systemic lupus erythematosus with and without medical contraindications to oestrogen.

OBJECTIVES: To assess the prevalence of combined hormonal contraceptives (CHCs) in reproductive-age women with SLE with and without possible contraindications and to determine factors associated with their use in the presence of possible contraindications. METHODS: This observational cohort study included premenopausal women ages 18-45 years enrolled in the SLICC Registry ⩽15 months after SLE onset, with annual assessments spanning 2000-2017. World Health Organization Category 3 or 4 contraindications to CHCs (e.g. hypertension, aPL) were assessed at each study visit. High disease activity (SLEDAI score >12 or use of >0.5 mg/kg/day of prednisone) was considered a relative contraindication. RESULTS: A total of 927 SLE women contributed 6315 visits, of which 3811 (60%) occurred in the presence of one or more possible contraindication to CHCs. Women used CHCs during 512 (8%) visits, of which 281 (55%) took place in the setting of one or more possible contraindication. The most frequently observed contraindications were aPL (52%), hypertension (34%) and migraine with aura (22%). Women with one or more contraindication were slightly less likely to be taking CHCs [7% of visits (95% CI 7, 8)] than women with no contraindications [9% (95% CI 8, 10)]. CONCLUSION: CHC use was low compared with general population estimates (>35%) and more than half of CHC users had at least one possible contraindication. Many yet unmeasured factors, including patient preferences, may have contributed to these observations. Further work should also aim to clarify outcomes associated with this exposure.

Power in numbers.

Collecting useful data on a sufficiently large cohort of pregnancies in women with rheumatic disease is a challenge. The original manuscripts that demonstrated the dangers of pregnancy in women with lupus were relatively small case series. As larger prospective cohorts were collected by university-based experts, however, greater safety was demonstrated and the current norms of treatment were determined. In recent years, larger administrative databases have been tapped to study pregnancies not managed within university clinics and to study the long-term impact of maternal rheumatic disease on the offspring. Each of these methods of study has both strengths and weaknesses, adding a unique piece of data to our overall knowledge. We will discuss a range of approaches to the study of rheumatic disease in pregnancy, covering the potential benefits that each brings as well as the biases that can impact study results. When the results of studies are viewed through these lenses, each can contribute to our larger understanding of the rheumatic diseases in pregnancy.

Postpartum complications in new mothers with juvenile idiopathic arthritis: a population-based cohort study.

Objective: The aim was to evaluate the prevalence of postpartum complications, including depression, in new mothers who had juvenile idiopathic arthritis (JIA) and to assess whether these differ from mothers who never had JIA. Methods: Our cohort study used data from physician billing and hospitalizations covering Quebec, Canada. We identified females with JIA with a first-time birth between 1 January 1983 and 31 December 2010 and assembled a control cohort of first-time mothers without JIA from the same administrative data, matching 4:1 for date of first birth, maternal age and area of residence. We compared the following postpartum complications: major puerperal infection, anaesthetic complications, postpartum haemorrhage, thromboembolism, obstetrical trauma, complications of obstetrical surgical wounds and maternal depression in the first year after delivery, in the JIA vs non-JIA groups, using bivariate analysis and multiple logistic regression. Results: The mean age at delivery was 24.7 years in the JIA group (n = 1681) and 25.0 years for the non-JIA group (n = 6724). Mothers with JIA were more likely to experience complications attributable to anaesthetic [adjusted risk ratio (aRR) 2.17, 95% CI; 1.05, 4.48], postpartum haemorrhage (aRR = 2.75, 95% CI: 2.42, 3.11) and thromboembolism (aRR = 5.27, 95% CI: 1.83, 15.17) but were at lower risk for obstetrical trauma (aRR = 0.78, 95% CI: 0.64, 0.95) or newly to develop depression in the first year postpartum (aRR = 0.52, 95% CI: 0.40, 0.68). Conclusion: Mothers with JIA appear to be at higher risk for complications attributable to anaesthesia, postpartum haemorrhage and thromboembolism. Prevention strategies for postpartum haemorrhage and thromboembolism may be especially important in this population.

SSRI and SNRI use during pregnancy and the risk of persistent pulmonary hypertension of the newborn.

AIM: The use of selective serotonin reuptake inhibitors (SSRIs) in late pregnancy may be associated with an increased risk of persistent pulmonary hypertension of the newborn (PPHN). Limited data are available on the risk of PPHN associated with serotonin norepinephrine reuptake inhibitors (SNRIs). We aimed to quantify both associations. METHODS: Using data from the Quebec Pregnancy Cohort between 1998 and 2009, we included women covered by the provincial drug plan who had a singleton live birth. Exposure categories were SSRI, SNRI and other antidepressant use; non-users were considered as the reference category. Generalized estimating equation models were used to obtain risk estimates and 95% confidence intervals (CIs). Confounding by indication was minimized by adjusting for history of maternal depression/anxiety before pregnancy. RESULTS: Overall, 143 281 pregnancies were included; PPHN was identified in 0.2% of newborns. Adjusting for maternal depression, and other potential confounders, SSRI use during the second half of pregnancy was associated with an increased risk of PPHN [adjusted odds ratio (aOR) 4.29, 95% CI 1.34, 13.77] compared with non-use of antidepressants; SNRI use during the same time window was not statistically associated with the risk of PPHN (aOR 0.59, 95% CI 0.06, 5.62). Use of SSRIs and SNRIs before the 20th week of gestation was not associated with the risk of PPHN. CONCLUSIONS: Use of SSRIs in the second half of pregnancy was associated with the risk of PPHN. Given our results on SNRIs and the lack of statistical power for these analyses, it is unclear whether SNRI use during pregnancy also increases the risk of PPHN.

Increased congenital heart defects in children born to women with systemic lupus erythematosus: results from the offspring of Systemic Lupus Erythematosus Mothers Registry Study.

BACKGROUND: In a large population-based study, we aimed to determine whether children born to women with systemic lupus erythematosus (SLE) have an increased risk of congenital heart defects (CHDs) in comparison with children born to women without SLE. METHODS AND RESULTS: The Offspring of SLE Mothers Registry (OSLER) includes all women who had ≥1 hospitalization for delivery after SLE diagnosis, identified through Quebec's healthcare databases (1989-2009), and a randomly selected control group of women, matched ≥4:1 for age and year of delivery. We identified children born live to SLE mothers and their matched controls, and ascertained CHD based on ≥1 hospitalization or physician visit with relevant diagnostic codes, within the first 12 months of life. We performed multivariable logistic regression analyses, using the generalized estimating equation method, to adjust for relevant covariates. Five hundred nine women with SLE had 719 children, whereas 5824 matched controls had 8493 children. In comparison with controls, children born to women with SLE experienced more CHD (5.2% [95% confidence interval (CI), 3.7-7.1] versus 1.9% [95% CI, 1.6-2.2], difference 3.3% [95% CI, 1.9-5.2]). In multivariable analyses, children born to women with SLE had a substantially increased risk of CHD (odds ratio, 2.62; 95% CI, 1.77-3.88) in comparison with controls. In addition, in comparison with controls, offspring of SLE mothers had a substantially increased risk of having a CHD repair procedure (odds ratio, 5.82; 95% CI, 1.77-19.09). CONCLUSIONS: In comparison with children from the general population, children born to women with SLE have an increased risk of CHD, and an increased risk of having a CHD repair procedure, as well.

Assessing process of care in rheumatoid arthritis at McGill University hospitals.

OBJECTIVE: In rheumatoid arthritis (RA), quality indicators (QIs) are tools used to measure process of care. This study aimed to assess performance of selected QIs from the 2004 Arthritis Foundation's QI Set at 2 major sites of a university network of teaching hospitals. METHODS: The charts and electronic hospital records of 76 RA patients were audited to determine adherence to QIs. Logistic multivariate regression analyses were performed to investigate potential determinants of nonadherence and propose measures to facilitate better QI compliance, as a potential strategy towards RA care improvement. RESULTS: We identified consistent observance of QIs mandating prescription of disease-modifying antirheumatic drug therapy for all patients, drug adjustment with disease activity, prednisone tapering, and bisphosphonate therapy if indicated for patients on glucocorticoids. However, there was either lack of documentation or true inconsistent adherence to QIs dealing with radiograph performance, functional capacity assessment, and screening for hepatitis and tuberculosis before commencement of methotrexate and biologic agents, respectively. For the specific QIs analyzed, we did not find any definite independent associations with the studied variables. CONCLUSIONS: Our findings indicate that while there is frequent evidence for adherence to certain RA quality care standards at our centers, there is less compliance to others. Strategies to optimize the performance or documentation of those found most lacking, namely, functional capacity and screening for specific drug contraindications, could improve patient care. Radiographic disease monitoring, while lacking, may represent a move toward other more sensitive methods of RA progression detection, such as joint ultrasound. The inclusion of patient- and physician-derived information could help elucidate the reasons underlying nonadherence.

Ustekinumab Safety in Pregnancy: A Comprehensive Review.

Chronic inflammatory conditions, including inflammatory bowel diseases (IBD), psoriasis, and psoriatic arthritis, are prevalent among women of reproductive age; patients with active disease during pregnancy may be at an increased risk of adverse birth outcomes. For this reason, physicians are focused on approaches to controlling disease activity prior to and during pregnancy. The safety profile of many therapies used for these conditions has been relatively well established, though evidence on newer therapies is lacking. Ustekinumab is a relatively new interleukin-12/23 inhibitor approved for IBD, psoriasis, and psoriatic arthritis, whose safety in pregnancy is not yet fully understood. In this comprehensive review, we critically assess the available evidence on ustekinumab in pregnancy across animal studies and human case reports, case series, observational studies, and clinical practice guidelines. We show that, to date, studies have not identified an excess risk of adverse pregnancy outcomes among women exposed to ustekinumab in pregnancy, with few exposed pregnancies and potential for some bias. Clinical guidelines are conflicted regarding whether they recommend continuing or discontinuing ustekinumab, highlighting the paucity of data and need for more research on this issue.

Trimethoprim-sulfamethoxazole prophylaxis during treatment of granulomatosis with polyangiitis with rituximab in the United States of America: a retrospective cohort study.

BACKGROUND: Antibiotic prophylaxis is recommended during ANCA-associated vasculitis (AAV) induction. We aimed to describe the frequency, persistence, and factors associated with trimethoprim-sulfamethoxazole (TMP-SMX) use in an adult population sample with granulomatosis with polyangiitis (GPA) treated with rituximab (RTX). METHODS: We identified adults with GPA treated with RTX within the Merative™ Marketscan® Research Databases (2011-2020). TMP-SMX prophylaxis was defined as a [Formula: see text] 28-day prescription dispensed within a month of starting RTX. We estimated TMP-SMX persistence, allowing prescription refill gaps of 30 days. Multivariable logistic regression and Cox proportional hazards regression assessed the factors associated with baseline TMP-SMX use and persistence, respectively. Covariates included age, sex, calendar year, insurance type, immunosuppressant use, hospitalization, and co-morbidities. RESULTS: Among 1877 RTX-treated GPA patients, the mean age was 50.9, and 54% were female. A minority (n = 426, 23%) received TMP-SMX with a median persistence of 141 (IQR 83-248) days. In multivariable analyses, prophylaxis was associated with prednisone use in the month prior to RTX ([Formula: see text] 20 mg/day vs none, OR 3.96; 95% CI 3.0-5.2; 1-19 mg/day vs none, OR 2.63; 95% CI 1.8-3.8), and methotrexate use (OR 1.48, 95% CI 1.04-2.1), intensive care (OR 1.95; 95% CI 1.4-2.7), and non-intensive care hospitalization (OR 1.56; 95% CI 1.2-2.1) in the 6 months prior to RTX. Female sex (OR 0.63; 95% CI 0.5-0.8) was negatively associated with TMP-SMX use. CONCLUSIONS: TMP-SMX was dispensed to a minority of RTX-treated GPA patients, more often to those on glucocorticoids and with recent hospitalization. Further research is needed to determine the optimal use and duration of TMP-SMX prophylaxis following RTX in AAV.

Outcomes associated with antiphospholipid antibodies in COVID-19: A prospective cohort study.

Background: The significance of antiphospholipid antibodies (aPL) in COVID-19 remains uncertain. Objectives: We determined whether aPL are associated with COVID-19 and/or thrombosis or adverse outcomes during hospitalization for COVID-19. Methods: Symptomatic adults tested for SARS-CoV-2 for clinical reasons (March-July 2020) with either ≥1 positive polymerase chain reaction (COVID-19+) or all negative (non-COVID-19) results were recruited to a biobank collecting plasma, clinical data, and outcomes. We tested baseline plasma samples (days 0-7) of all subjects (and day-30 samples in the COVID-19+ subjects, when available) for aPL (anticardiolipin immunoglobulin [Ig]M/IgG, anti-ß2-glycoprotein I IgM/IgG, antiphosphatidylserine/prothrombin IgM/IgG, and lupus anticoagulant). We compared the baseline prevalence of aPL between the COVID-19+ and non-COVID-19 subjects. Among hospitalized COVID-19+ subjects, multivariable logistic regression was used to evaluate the association of aPL (and their subtypes) with arterial or venous thromboembolic events, acute kidney injury, intensive care unit admission, mechanical ventilation, and death after adjusting for potential confounders. Results: At baseline, 123 of 289 (43%) COVID+ subjects had ≥1 aPL versus 116 of 261 (32%) non-COVID-19 subjects (difference, 10%; 95% CI, 3%-18%). Among 89 COVID+ subjects with repeated samples, aPL persisted on day 30 in 15 of 34 (44%) subjects with baseline aPL positivity, and half of those without aPL at baseline developed one or more new aPL. In hospitalized COVID-19 subjects (n = 241), baseline aPL positivity was associated with acute kidney injury (odds ratio [OR], 1.8; 95% CI, 1.1-3.2) and mechanical ventilation (OR, 3.2; 95% CI, 1.5-6.8) but not death (OR, 1.2; 95% CI, 0.6-2.5). In secondary analyses, medium-to-high titers of anticardiolipin IgG (>40) were associated with thromboembolic events (OR, 7.3; 95% CI, 1.8-30.1). Conclusion: In patients with COVID-19, aPL may help identify an increased risk of thrombosis and other adverse outcomes.

Assessing Serious Infections in Children Exposed In Utero to Ustekinumab.

Chronic inflammatory conditions, including inflammatory bowel disease (IBD), psoriasis (PsO), and psoriatic arthritis (PsA), have a high burden among women of reproductive age. There has been significant interest in finding safe ways of controlling disease activity during pregnancy without adversely affecting the pregnancy or offspring.

Measuring the Impact of MyLupusGuide in Canada: Results of a Randomized Controlled Study.

OBJECTIVE: This study was undertaken to assess the effects of a web-based program, MyLupusGuide, developed to facilitate self-management in systemic lupus erythematosus (SLE). METHODS: In this randomized controlled online study, participants received either immediate access to the MyLupusGuide site or delayed access starting on month 3. The primary outcome was the patient activation measure (PAM) score. Secondary outcomes included measurements of health status, self-efficacy, coping, perceived patient-physician relationship, and medication adherence. Outcomes were measured at the baseline visit and at the 3-month and 6-month follow-up visits. We used linear mixed modeling to compare PAM scores between the 2 groups at months 3 and 6. RESULTS: There were 541 participants included in this study. The mean ± SE age was 50 ± 14 years; 93% were female and 74% were White. The mean ± SE disease duration was 17 ± 12 years, and 56% visited MyLupusGuide at least once. The baseline mean ± SE PAM score was 61.2 ± 13, with 36% scoring low for perceived self-management skills. After 3 months of exposure to MyLupusGuide, there were no differences in terms of PAM scores between groups. In exploratory analyses, we found significant improvement in PAM scores in those who had low PAM scores at baseline and in male individuals. We observed significant improvements in self-efficacy before and after access to MyLupusGuide and delayed improvements at month 6 compared to month 3 in terms of mental health and emotional coping. CONCLUSION: MyLupusGuide increases self-efficacy but not patient activation. A total of 56% of participants visited the MyLupusGuide site during the study period. Individuals with lupus need support to become activated toward self-management behaviors.