9A.07: CARDIOVASCULAR TARGET ORGAN DAMAGE IN PREMENOPAUSAL SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS AND IN CONTROLS. ARE THERE ANY DIFFERENCES?

OBJECTIVE: In patients with systemic lupus erythematosus (SLE) a greater prevalence of structural and functional cardiovascular (CV) alterations has been described, possibly explaining the higher incidence of CV events, as compared to subjects matched for age and sex.Aim of this study was to analyze the presence of target organ damage in premenopausal women with SLE and in controls matched not only for demographic characteristics but also for other cardiovascular risk factors. DESIGN AND METHOD: 34 patients with SLE clinically stable (SLEDAI Score 2.5 +/- 1.5) (mean age 32 ± 7 years, range 19-44) and 34 controls matched for sex, age, body mass index (BMI), clinic blood pressure (BP) and antihypertensive treatment (if present), underwent: 24 hours BP monitoring, echocardiography with tissue Doppler analysis (TDI) for the evaluation of left ventricular (LV) structure and of systolic and diastolic function, carotid ultrasound for intima-media thickness (IMT) and carotid distensibility measurement, and pulse wave velocity measurement for aortic stiffness (PWV). RESULTS: By definition no difference was observed for age, sex, BMI and clinic BP values and a similar Framingham risk score was observed between SLE and controls (1.3 ± 2.7 vs 1.5 ± 2.3%, p = ns). No significant differences were observed for all echocardiographic parameters except LV longitudinal systolic function (Sm), an early index of LV systolic dysfunction (see Table). Carotid IMT and distensibility, as well as PWV and the prevalence of an abnormal aortic stiffness were both similar in the two groups. At the logistic analysis, PWV was independently associated with LV mass in controls and with the steroid weekly dose in SLE patients.(Figure is included in full-text article.) CONCLUSIONS: In patients with SLE and low activity index of the disease we did not observe significant vascular alterations as compared to controls with similar cardiovascular risk. The early LV systolic impairment observed in this group of patients needs confirmation in larger cohorts

Ten Year Risk of Cardiovascular Events during anti-TNF Alpha in Rheumatoid Arthritis Patients

Abstract Objective: To analyze the rate of major CV events in 433 patients with longstanding RA, treated for more than 10 years with anti-TNFα or DMARDs. Methods: All RA patients treated with anti-TNF-α from 2000 and 2002 (n. 86; TNF+ group) and a random sample of 258 patients treated with DMARDs out of 829 followed-up in the same period in the same Unit (TNF- group) were analyzed. Myocardial infarction, heart failure, stroke, transient cerebral ischemic attack were considered. Exposure (anti-TNF-α vs. DMARDs) and outcome (CV events) were analyzed by the proportional hazard Cox regression, adjusting for RA duration, DAS 28, seropositivity (RF, anti CCP), treatment and Framingham CV risk factors (adjusted according to EULAR recommendations). Results: CV events were detected in 18.9% of cases with an incidence rate of 2.4% patients/year (95%CI: 1.5-3.7) in TNF+ and 1.3% patients/year (95%CI: 0.9-1.7) in TNF- group. Events occurred after a mean of 8.3 ± 3.6 years of anti-TNF exposure and 13.3 ± 8 years of DMARDs exposure (p: 0.006). Cox analysis, adjusted for sex, age, CV risk factors, DAS28, FR positivity, corticosteroids, anti-inflammatory drugs and methotrexate treatment, showed that only Framingham risk score is slightly associated with CV events (HR: 1.03, 95%CI:1.01-1.06). In addition, diabetes (p: 0.017) and coronary artery disease (p: 0.015) were associated with myocardial infarction, while higher age at RA onset (p: 0.02) and Framingham risk score (p: 0.0008) were associated with heart failure. Conclusions: CV events occurred in 2.4% patient/year during anti-TNF alpha treatment. A strict cardiovascular monitoring was mandatory in order to prevent major CV events

A comprehensive review of the clinical approach to pregnancy and systemic lupus erythematosus

Nowadays, most of the young women affected by Systemic Lupus Erythematosus (SLE) can carry out one or more pregnancies thanks to the improvement in treatment and the consequent reduction in morbidity and mortality. Pregnancy outcome in these women has also greatly improved in the last decades. A correct timing for pregnancy (tailored on disease activity and established during a preconception counselling), together with a tight monitoring during the three trimesters and the post-partum period (to timely identify and treat possible obstetric complications or maternal disease flares), as well as the concept of multidisciplinary management, are currently milestones of the management of pregnancy in SLE patients. Nevertheless, the increasing knowledge on the compatibility of drugs with pregnancy has allowed a better treatment of these patients, by choosing medications that control maternal disease activity without harming the foetus. However, particular attention and strict monitoring should be dedicated to SLE pregnant women in particular clinical settings: patients with lupus nephritis and patients with aPL positivity or Antiphospholipid syndrome, who are at higher risk for maternal and foetal complications, but also patients with anti-Ro/SSA and/or anti-La/SSB antibodies, because of the risk of neonatal lupus. A discussion on family planning, as well as counselling on contraception, should be part of the everyday-practice for physicians caring for SLE women during their reproductive age. Another issue is the possible reduction of fertility in these women, that can be due to different reasons. Consequently, the request for assisted reproduction techniques has been increasing in the last years, so that rheumatologists and gynaecologists should be prepared to counsel SLE patients also in this particular setting

Preverbal productions in children with sex chromosome trisomies

Supplemental material for "Preverbal skills in 8-month-old children with sex chromosome trisomies" in First Languag

9A.07

OBJECTIVE: In patients with systemic lupus erythematosus (SLE) a greater prevalence of structural and functional cardiovascular (CV) alterations has been described, possibly explaining the higher incidence of CV events, as compared to subjects matched for age and sex.Aim of this study was to analyze the presence of target organ damage in premenopausal women with SLE and in controls matched not only for demographic characteristics but also for other cardiovascular risk factors. DESIGN AND METHOD: 34 patients with SLE clinically stable (SLEDAI Score 2.5 +/- 1.5) (mean age 32 ± 7 years, range 19-44) and 34 controls matched for sex, age, body mass index (BMI), clinic blood pressure (BP) and antihypertensive treatment (if present), underwent: 24 hours BP monitoring, echocardiography with tissue Doppler analysis (TDI) for the evaluation of left ventricular (LV) structure and of systolic and diastolic function, carotid ultrasound for intima-media thickness (IMT) and carotid distensibility measurement, and pulse wave velocity measurement for aortic stiffness (PWV). RESULTS: By definition no difference was observed for age, sex, BMI and clinic BP values and a similar Framingham risk score was observed between SLE and controls (1.3 ± 2.7 vs 1.5 ± 2.3%, p = ns). No significant differences were observed for all echocardiographic parameters except LV longitudinal systolic function (Sm), an early index of LV systolic dysfunction (see Table). Carotid IMT and distensibility, as well as PWV and the prevalence of an abnormal aortic stiffness were both similar in the two groups. At the logistic analysis, PWV was independently associated with LV mass in controls and with the steroid weekly dose in SLE patients.(Figure is included in full-text article.) CONCLUSIONS: In patients with SLE and low activity index of the disease we did not observe significant vascular alterations as compared to controls with similar cardiovascular risk. The early LV systolic impairment observed in this group of patients needs confirmation in larger cohorts

Longterm outcome of patients with primary antiphospholipid syndrome: A retrospective multicenter study

Objective. To assess the longterm frequency of thrombotic recurrences, obstetrical complications, organ damage, severe comorbidities, and evolution toward connective tissue disease (CTD) in primary antiphospholipid syndrome (PAPS). Methods.Medical records of patients with PAPS followed in 6 centers for 65 15 years were retrospectively reviewed. Results. One hundred fifteen patients were studied: 88% women, followed between 1983 and 2014 with a mean (\ub1 SD) age at diagnosis of 33 (\ub1 10) years. During a median followup of 18 years (range 15-30), 50 patients (44%) had at least a thrombotic event for a total of 75 events and an annual incidence of 3.5%. Thromboses were more frequent in patients with previous thrombotic history (p = 0.002). A catastrophic antiphospholipid syndrome occurred in 6 patients (5%). The use of oral anticoagulants in patients with thrombotic onset did not appear to be protective against recurrences (p = 0.26). Fifty-two women had 87 pregnancies, successful in 78%. Twenty-nine percent of patients accrued functional damage. Damage was significantly associated with a thrombotic history (p = 0.004) and with arterial events (p < 0.001), especially stroke, but not with demographics, serology, or treatment. Twenty-four major bleeding episodes were recorded in 18 patients, all receiving anticoagulants. Severe infections affected 6 patients (5%), with 1 fatality. A solid cancer was diagnosed in 8 patients (7%). Altogether, 16 patients (14%) developed an autoimmune disease and 13 (11%) a full-blown picture of CTD. Conclusion. Despite therapy, a high proportion of patients experienced new thrombotic events and organ damage, while evolution toward CTD was infrequent

“Disease knowledge index” and perspectives on reproductive issues: A nationwide study on 398 women with autoimmune rheumatic diseases

Objective: The reproductive choices of women affected by rheumatic diseases (RD) can be influenced by several factors, including the quality of physician-patient communication. We conducted a survey on reproductive issues aiming at exploring the unmet needs of women with RD during childbearing age. Methods: We administered 65 multiple-choice and 12 open-answer questions about pregnancy counselling, contraception, use of drugs during pregnancy and other women reproductive issues to 477 consecutive women with RD aged 18–55 years followed-up in 24 rheumatology centres in Italy. Analysis was restricted to 398 patients who received their diagnosis of RD before the age of 45. According to the RD diagnosis, patients were subdivided into 2 groups: connective tissue diseases (n = 249) and chronic arthritis (n = 149). Results: At the time of interview, women in both groups had a mean age of 40 years. Nearly one third of patients in each group declared not to have received any counselling about either pregnancy desire nor contraception. A smaller family size than desired was reported by nearly 37% of patients, because of concerns related to maternal disease in one fourth of the cases. A “Disease Knowledge Index” (DKI) was created to investigate the degree of patients’ information about the implications of their RD on reproductive issues. Having received counselling was associated with higher DKI values and with a positive impact on family planning. Conclusion: Italian women of childbearing age affected by RD reported several unmet needs in their knowledge about reproductive issues. Strategies are needed to implement and facilitate physician-patient communication

A Prospective International Study on Adherence to Treatment in 305 Patients With Flaring SLE: Assessment by Drug Levels and Self-Administered Questionnaires

Nonadherence to treatment is a major cause of lupus flares. Hydroxychloroquine (HCQ), a major medication in systemic lupus erythematosus, has a long half-life and can be quantified by high-performance liquid chromatography. This international study evaluated nonadherence in 305 lupus patients with flares using drug levels (HCQ <200 ng/ml or undetectable desethylchloroquine), and self-administered questionnaires (MASRI <80% or MMAS-8 <6). Drug levels defined 18.4% of the patients as severely nonadherent. In multivariate analyses, younger age, nonuse of steroids, higher body mass index, and unemployment were associated with nonadherence by drug level. Questionnaires classified 39.9% of patients as nonadherent. Correlations between adherence measured by questionnaires, drug level, and physician assessment were moderate. Both methods probably measured two different patterns of nonadherence: self-administered questionnaires mostly captured relatively infrequently missed tablets, while drug levels identified severe nonadherence (i.e., interruption or erratic tablet intake). The frequency with which physicians miss nonadherence, together with underreporting by patients, suggests that therapeutic drug monitoring is useful in this setting. (Trial registration: ClinicalTrials.gov: NCT01509989.)

A Prospective International Study on Adherence to Treatment in 305 Patients With Flaring SLE: Assessment by Drug Levels and Self-Administered Questionnaires [Corrected and republished]

Nonadherence to treatment is a major cause of lupus flares. Hydroxychloroquine (HCQ), a major medication in systemic lupus erythematosus, has a long half-life and can be quantified by high-performance liquid chromatography. This international study evaluated nonadherence in 305 lupus patients with flares using drug levels (HCQ < 200 ng/ml or undetectable desethylchloroquine), and self-administered questionnaires (MASRI < 80%). Drug levels defined 18.4% of the patients as severely nonadherent. In multivariate analyses, younger age, nonuse of steroids, higher body mass index, and unemployment were associated with nonadherence by drug level. Questionnaires classified 23.4% of patients as nonadherent. Correlations between adherence measured by questionnaires, drug level, and physician assessment were moderate. Both methods probably measured two different patterns of nonadherence: self-administered questionnaires mostly captured relatively infrequently missed tablets, while drug levels identified severe nonadherence (i.e., interruption or erratic tablet intake). The frequency with which physicians miss nonadherence, together with underreporting by patients, suggests that therapeutic drug monitoring is useful in this setting. (Trial registration: ClinicalTrials.gov: NCT01509989.)

Systemic sclerosis Progression INvestiGation (SPRING) Italian registry: demographic and clinico-serological features of scleroderma spectrum

Systemic sclerosis (SSc) is a severe multiple-organ disease characterised by unpredictable clinical course, inadequate response to treatment, and poor prognosis. National SSc registries may provide large and representative patients cohorts required for descriptive and prognostic studies. Therefore, the Italian Society of Rheumatology promoted the registry SPRING (Systemic sclerosis Progression INvestiGation)