173 Immunosuppressant discontinuation in systemic lupus erythematosus: prevalence, risk of subsequent flare and effect on damage accrual

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THU0267 THE SLE DISEASE ACTIVITY SCORE (SLE-DAS) ENABLES ACCURATE DEFINITIONS OF SLE REMISSION AND LDA AS ACHIEVABLE TARGETS IN DISEASE MANAGEMENT

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Radio Recombination Lines toward the Galactic Center Lobe

The Galactic Center lobe is a degree-tall shell seen in radio continuum images of the Galactic center (GC) region. If it is actually located in the GC region, formation models would require massive energy input (e.g., starburst or jet) to create it. At present, observations have not strongly constrained the location or physical conditions of the GC lobe. This paper describes the analysis of new and archival single-dish observations of radio recombination lines toward this enigmatic object. The observations find that the ionized gas has a morphology similar to the radio continuum emission, suggesting that they are associated. We study averages of several transitions from H106alpha to H191epsilon and find that the line ratios are most consistent with gas in local thermodynamic equilibrium. The radio recombination line widths are remarkably narrow, constraining the typical electron temperature to be less than about 4000 K. These observations also find evidence of pressure broadening in the higher electronic states, implying a gas density of n_e=910^{+310}_{-450} cm^{-3}. The electron temperature, gas pressure, and morphology are all consistent with the idea that the GC lobe is located in the GC region. If so, the ionized gas appears to form a shell surrounding the central 100 parsecs of the galaxy with a mass of roughly 10^5 Msun, similar to ionized outflows seen in dwarf starbursts.Comment: Accepted to ApJ. 17 pages, 9 figures, emulateapj styl

Derivation and validation of the SLE Disease Activity Score (SLE-DAS): a new SLE continuous measure with high sensitivity for changes in disease activity

Objectives To derive and validate a new disease activity measure for systemic lupus erythematosus (SLE), the SLE Disease Activity Score (SLE-DAS), with improved sensitivity to change as compared with SLE Disease Activity Index (SLEDAI), while maintaining high specificity and easiness of use. Methods We studied 520 patients with SLE from two tertiary care centres (derivation and validation cohorts). At each visit, disease activity was scored using the Physician Global Assessment (PGA) and SLEDAI 2000 (SLEDAI-2K). To construct the SLE-DAS, we applied multivariate linear regression analysis in the derivation cohort, with PGA as dependent variable. The formula was validated in a different cohort through the study of: (1) correlations between SLE-DAS, PGA and SLEDAI-2K; (2) performance of SLEDAI-2K and SLE-DAS in identifying a clinically meaningful change in disease activity (ΔPGA≥0.3); and (3) accuracy of SLEDAI-2K and SLE-DAS time-adjusted means in predicting damage accrual. Results The final SLE-DAS instrument included 17 items. SLE-DAS was highly correlated with PGA (r=0.875, p<0.0005) and SLEDAI-2K (r=0.943, p<0.0005) in the validation cohort. The optimal discriminative ΔSLE-DAS cut-off to detect a clinically meaningful change was 1.72. In the validation cohort, SLE-DAS showed a higher sensitivity than SLEDAI-2K (change ≥4) to detect a clinically meaningful improvement (89.5% vs 47.4%, p=0.008) or worsening (95.5% vs 59.1%, p=0.008), while maintaining similar specificities. SLE-DAS performed better in predicting damage accrual than SLEDAI-2K. Conclusion SLE-DAS has a good construct validity and has better performance than SLEDAI-2K in identifying clinically significant changes in disease activity and in predicting damage accrual.info:eu-repo/semantics/publishedVersio

Control of star formation by supersonic turbulence

Understanding the formation of stars in galaxies is central to much of modern astrophysics. For several decades it has been thought that stellar birth is primarily controlled by the interplay between gravity and magnetostatic support, modulated by ambipolar diffusion. Recently, however, both observational and numerical work has begun to suggest that support by supersonic turbulence rather than magnetic fields controls star formation. In this review we outline a new theory of star formation relying on the control by turbulence. We demonstrate that although supersonic turbulence can provide global support, it nevertheless produces density enhancements that allow local collapse. Inefficient, isolated star formation is a hallmark of turbulent support, while efficient, clustered star formation occurs in its absence. The consequences of this theory are then explored for both local star formation and galactic scale star formation. (ABSTRACT ABBREVIATED)Comment: Invited review for "Reviews of Modern Physics", 87 pages including 28 figures, in pres

EULAR recommendations for the non-pharmacological management of systemic lupus erythematosus and systemic sclerosis

Objective To develop evidence-based recommendations for the non-pharmacological management of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Methods A task force comprising 7 rheumatologists, 15 other healthcare professionals and 3 patients was established. Following a systematic literature review performed to inform the recommendations, statements were formulated, discussed during online meetings and graded based on risk of bias assessment, level of evidence (LoE) and strength of recommendation (SoR; scale AD , A comprising consistent LoE 1 studies, D comprising LoE 4 or inconsistent studies), following the European Alliance of Associations for Rheumatology standard operating procedure. Level of agreement (LoA; scale 0-10, 0 denoting complete disagreement, 10 denoting complete agreement) was determined for each statement through online voting. Results Four overarching principles and 12 recommendations were developed. These concerned common and disease-specific aspects of non-pharmacological management. SoR ranged from A to D. The mean LoA with the overarching principles and recommendations ranged from 8.4 to 9.7. Briefly, non-pharmacological management of SLE and SSc should be tailored, person-centred and participatory. It is not intended to preclude but rather complement pharmacotherapy. Patients should be offered education and support for physical exercise, smoking cessation and avoidance of cold exposure. Photoprotection and psychosocial interventions are important for SLE patients, while mouth and hand exercises are important in SSc. Conclusions The recommendations will guide healthcare professionals and patients towards a holistic and personalised management of SLE and SSc. Research and educational agendas were developed to address needs towards a higher evidence level, enhancement of clinician-patient communication and improved outcomes

EULAR recommendations for the non-pharmacological management of systemic lupus erythematosus and systemic sclerosis

Objective To develop evidence-based recommendations for the non-pharmacological management of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Methods A task force comprising 7 rheumatologists, 15 other healthcare professionals and 3 patients was established. Following a systematic literature review performed to inform the recommendations, statements were formulated, discussed during online meetings and graded based on risk of bias assessment, level of evidence (LoE) and strength of recommendation (SoR; scale A–D, A comprising consistent LoE 1 studies, D comprising LoE 4 or inconsistent studies), following the European Alliance of Associations for Rheumatology standard operating procedure. Level of agreement (LoA; scale 0–10, 0 denoting complete disagreement, 10 denoting complete agreement) was determined for each statement through online voting. Results Four overarching principles and 12 recommendations were developed. These concerned common and disease-specific aspects of non-pharmacological management. SoR ranged from A to D. The mean LoA with the overarching principles and recommendations ranged from 8.4 to 9.7. Briefly, non-pharmacological management of SLE and SSc should be tailored, person-centred and participatory. It is not intended to preclude but rather complement pharmacotherapy. Patients should be offered education and support for physical exercise, smoking cessation and avoidance of cold exposure. Photoprotection and psychosocial interventions are important for SLE patients, while mouth and hand exercises are important in SSc. Conclusions The recommendations will guide healthcare professionals and patients towards a holistic and personalised management of SLE and SSc. Research and educational agendas were developed to address needs towards a higher evidence level, enhancement of clinician–patient communication and improved outcomes

Influence of safety warnings on the prescribing attitude of JAK 2inhibitors for rheumatoid arthritis in Italy

The Janus kinase inhibitors (JAKi) tofacitinib (TOFA), baricitinib (BARI), upadacitinib (UPA) and 74 filgotinib (FILGO) are effective drugs for the treatment of rheumatoid arthritis. However, the US 75 Food &amp; Administration (FDA) raised concerns on the safety of TOFA after its approval. This 76 prompted the European Medicines Agency (EMA) to issue two safety warnings for limiting TOFA 77 use then extended in a third warning to all Jaki in patients at high risk of developing serious adverse 78 events (SAE). These included thrombosis, major adverse cardiac events (MACE) and cancer. Thepurpose of this work was to analyze how the first two safety warnings from EMA affected the pre- 80 scribing of Jaki by rheumatologists in Italy. All patients with rheumatoid arthritis who had been 81 prescribed JAKi for the first time in a 36-month period from July 1, 2019, to June 30, 2022 were con- 82 sidered. Data were obtained from the medical records of 29 Italian tertiary referral rheumatology 83 centers. Patients were divided into three groups of 4 months each, depending on whether the JAKi 84 prescription had occurred before the EMA's first safety alert (July 1-October 31, 2019, Group 1), 85 between the first and second alerts (November 1, 2019-February 29, 2020, Group 2), or between the 86 second and third alerts (March 1, 2021-June 30, 2021, Group 3). Percentage and absolute changes in 87 patients prescribed the individual JAKi were analyzed. Differences among the three Groups of pa- 88 tients in demographic and clinical characteristics were also assessed. A total of 864 patients were 89 prescribed a JAKi during the entire period considered. Of these, 343 were identified in Group 1, 233 90 in Group 2 and 288 in Group 3. An absolute reduction of 32% was observed in the number of patients 91 prescribed a JAKi between Group 1 and Group 2 and 16% between Group 1 and Group 3. In contrast, 92 there was a 19% increase in the prescription of a JAKi in patients between Group 2 and Group 3. In 93 the first Group, BARI was the most prescribed drug (227 prescriptions, 66.2% of the total), followed 94 by TOFA (115, 33.5%) and UPA (1, 0.3%). In the second Group, the most prescribed JAKi was BARI 95 (147, 63.1%), followed by TOFA (65, 27.9%) and UPA (33, 11.5%). In the third Group, BARI was still 96 the most prescribed JAKi (104 prescriptions, 36.1%), followed by UPA (89, 30.9%), FILGO (89, 21.5%) 97 and TOFA (33, 11.5%). The number of patients prescribed TOFA decreased significantly between 98 Group 1 and Group 2 and between Group 2 and Group 3 (p ˂ 0.01). Patients who were prescribed 99 BARI decreased significantly between Group 1 and Group 2 and between Group 2 and Group 3 (p 100 ˂ 0.01). In contrast, patients prescribed UPA increased between Group 2 and Group 3 (p ˂ 0.01). 101 These data suggest that the warnings issued for TOFA were followed by a reduction in total JAKi 102 prescriptions. However, the more selective JAKi (UPA and FILGO) were perceived by prescribers 103 as favorable in terms of risk/benefit ratio and their use gradually increased at the expense of the 104 other molecules

Management of pregnancy in autoimmune rheumatic diseases: maternal disease course, gestational and neonatal outcomes and use of medications in the prospectiveItalian P-RHEUM.it study

Objectives To investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it. Methods Pregnant women with different ARD were enrolled for up to 20 gestational weeks in 29 Rheumatology Centres for 5 years (2018-2023). Maternal and infant information were collected in a web-based database. Results We analysed 866 pregnancies in 851 patients (systemic lupus erythematosus was the most represented disease, 19.6%). Maternal disease flares were observed in 135 (15.6%) pregnancies. 53 (6.1%) pregnancies were induced by assisted reproduction techniques, 61 (7%) ended in miscarriage and 11 (1.3%) underwent elective termination. Obstetrical complications occurred in 261 (30.1%) pregnancies, including 2.3% pre-eclampsia. Two cases of congenital heart block were observed out of 157 pregnancies (1.3%) with anti-Ro/SSA. Regarding treatments, 244 (28.2%) pregnancies were treated with glucocorticoids, 388 (44.8%) with hydroxychloroquine, 85 (9.8%) with conventional synthetic disease-modifying anti-rheumatic drugs and 122 (14.1%) with biological disease-modifying anti-rheumatic drugs. Live births were 794 (91.7%), mostly at term (84.9%); four perinatal deaths (0.5%) occurred. Among 790 newborns, 31 (3.9%) were small-for-gestational-age and 169 (21.4%) had perinatal complications. Exclusive maternal breast feeding was received by 404 (46.7%) neonates. The Edinburgh Postnatal Depression Scale was compiled by 414 women (52.4%); 89 (21.5%) scored positive for emotional distress. Conclusions Multiple factors including preconception counselling and treat-to-target with pregnancy-compatible medications may have contributed to mitigate disease-related risk factors, yielding limited disease flares, good pregnancy outcomes and frequency of complications which were similar to the Italian general obstetric population. Disease-specific issues need to be further addressed to plan preventative measures

THE ROLE OF PENTRAXIN-3 AS PREDICTOR OF PREGNANCY COMPLICATIONS IN PATIENTS WITH SLE AND/OR ANTI-PHOSPHOLIPID SYNDROME AND APL CARRIERS

Systemic Lupus Erythematosus (SLE) is an autoimmune disease affecting childbearing women. Nowadays, mainly due to preconception counselling, the overall prognosis of such pregnancies has consistently improved. Preconception visit is pivotal to assess anti-phospholipid (aPL) antibodies and/or anti-phospholipid syndrome (APS), drugs’ safety and disease activity, in order to prevent adverse pregnancy outcomes (APOs) and maternal flares. The general aim of the thesis was to improve the management of pregnant SLE and/or APS patients by assessing pregnancy outcomes and identifying predictors of APOs and flares. Firstly, we focused on severe preeclampsia (PE) leading to preterm delivery<34 weeks, which is one of the classification criteria of APS. The sample included 40 APS patients with severe PE enrolled in 6 European centres. PE occurred very early in gestation (median 25.5 weeks) and with a high mortality during the offspring (65%). In the follow-up period (5 years), none of these patients experienced 3 consecutive miscarriages, whereas thromboses, intrauterine foetal deaths and HELLP syndromes were observed, suggesting that recurrent miscarriages APS criterion may have a different physiopathology compared to the other criteria. Secondly, we tested a new score, the SLE-disease activity score (SLE-DAS) as predictor of flares and APOs in 2nd and 3rd trimester in SLE women enrolled at two referral centres (Italy and France). SLE activity was assessed at first trimester by SLE-pregnancy disease activity index (SLEPDAI) and SLE-DAS. In this cohort of 158 pregnant patients with a very stable lupus, a significant correlation between SLE-DAS and SLEPDAI was observed (Spearman’s ρ=0.97). Both SLE-DAS and SLEPDAI predicted flares (p=0.02 and p=0.01, respectively), and resulted associated with APOs (p=0.02). Thus, SLE-DAS seems a reliable instrument to measure SLE activity during pregnancy. Planning pregnancy when SLE is quiescent is a cornerstone of the management of SLE patients. However, the impact of lupus low disease activity state (LLDAS), remission and damage accrual in early gestation has never been simultaneously studied. We evaluated SLE women in the prospective GR2 study with an ongoing singleton pregnancy at 12 weeks (one pregnancy/woman). Several sets of criteria were used to define remission, disease activity, and damage. First trimester maternal and SLE features were tested as predictors of flares and APOs. 238 women (98.3% on hydroxychloroquine) had 230 live births. Thirty-five (14.7%) patients had at least one flare; APOs occurred in 34 (14.3%) women. At logistic regression models, damage (SLICC-Damage Index) (odds ratio-OR- 1.8, 95% confidence intervals-CI-: 1.1-2.9 for model 1 and OR 1.7, 95% CI: 1.1-2.8 for model 2) and lupus anticoagulant (LAC, OR 4.2, 95% CI: 1.8-9.7 for model 1; OR 3.7, 95% CI: 1.6-8.7 for model 2) resulted significantly associated with APOs. Hence, damage should be considered in preconception counselling and early gestation along with LAC. Pentraxin-3 (PTX3) has been studied as promising biomarker of pregnancy complications, although no data on SLE/APS pregnant women are available. Hence, we evaluated serum PTX-3 and anti-PTX3 antibodies as predictors of pregnancy outcomes in SLE and/or APS women at our Rheumatology Unit. The current analysis included pregnant SLE (SLICC 2012) and/or APS (Sydney, 2006) women. The control group included healthy patients/affected with other rheumatic diseases (nor SLE nor APS) referred to our clinic with a conception date <1st April 2021 (one pregnancy/patient). Among 79 pregnancies, APS occurred in 7 (8.9%), SLE in 9 (11.4%) and SLE with APS in 3 women (3,8%). Overall, the control group included 66 (83.6%) patients. Serum IgG anti-PTX3 Abs were found in 11 (13.9%, 95% CI 7.2-23.5) women. Anti-PTX3 were slightly associated with gestational diabetes mellitus (GDM) (p=0.04) and resulted slightly associated with intra-uterine growth restriction (p=0.09).Systemic Lupus Erythematosus (SLE) is an autoimmune disease affecting childbearing women. Nowadays, mainly due to preconception counselling, the overall prognosis of such pregnancies has consistently improved. Preconception visit is pivotal to assess anti-phospholipid (aPL) antibodies and/or anti-phospholipid syndrome (APS), drugs’ safety and disease activity, in order to prevent adverse pregnancy outcomes (APOs) and maternal flares. The general aim of the thesis was to improve the management of pregnant SLE and/or APS patients by assessing pregnancy outcomes and identifying predictors of APOs and flares. Firstly, we focused on severe preeclampsia (PE) leading to preterm delivery<34 weeks, which is one of the classification criteria of APS. The sample included 40 APS patients with severe PE enrolled in 6 European centres. PE occurred very early in gestation (median 25.5 weeks) and with a high mortality during the offspring (65%). In the follow-up period (5 years), none of these patients experienced 3 consecutive miscarriages, whereas thromboses, intrauterine foetal deaths and HELLP syndromes were observed, suggesting that recurrent miscarriages APS criterion may have a different physiopathology compared to the other criteria. Secondly, we tested a new score, the SLE-disease activity score (SLE-DAS) as predictor of flares and APOs in 2nd and 3rd trimester in SLE women enrolled at two referral centres (Italy and France). SLE activity was assessed at first trimester by SLE-pregnancy disease activity index (SLEPDAI) and SLE-DAS. In this cohort of 158 pregnant patients with a very stable lupus, a significant correlation between SLE-DAS and SLEPDAI was observed (Spearman’s ρ=0.97). Both SLE-DAS and SLEPDAI predicted flares (p=0.02 and p=0.01, respectively), and resulted associated with APOs (p=0.02). Thus, SLE-DAS seems a reliable instrument to measure SLE activity during pregnancy. Planning pregnancy when SLE is quiescent is a cornerstone of the management of SLE patients. However, the impact of lupus low disease activity state (LLDAS), remission and damage accrual in early gestation has never been simultaneously studied. We evaluated SLE women in the prospective GR2 study with an ongoing singleton pregnancy at 12 weeks (one pregnancy/woman). Several sets of criteria were used to define remission, disease activity, and damage. First trimester maternal and SLE features were tested as predictors of flares and APOs. 238 women (98.3% on hydroxychloroquine) had 230 live births. Thirty-five (14.7%) patients had at least one flare; APOs occurred in 34 (14.3%) women. At logistic regression models, damage (SLICC-Damage Index) (odds ratio-OR- 1.8, 95% confidence intervals-CI-: 1.1-2.9 for model 1 and OR 1.7, 95% CI: 1.1-2.8 for model 2) and lupus anticoagulant (LAC, OR 4.2, 95% CI: 1.8-9.7 for model 1; OR 3.7, 95% CI: 1.6-8.7 for model 2) resulted significantly associated with APOs. Hence, damage should be considered in preconception counselling and early gestation along with LAC. Pentraxin-3 (PTX3) has been studied as promising biomarker of pregnancy complications, although no data on SLE/APS pregnant women are available. Hence, we evaluated serum PTX-3 and anti-PTX3 antibodies as predictors of pregnancy outcomes in SLE and/or APS women at our Rheumatology Unit. The current analysis included pregnant SLE (SLICC 2012) and/or APS (Sydney, 2006) women. The control group included healthy patients/affected with other rheumatic diseases (nor SLE nor APS) referred to our clinic with a conception date <1st April 2021 (one pregnancy/patient). Among 79 pregnancies, APS occurred in 7 (8.9%), SLE in 9 (11.4%) and SLE with APS in 3 women (3,8%). Overall, the control group included 66 (83.6%) patients. Serum IgG anti-PTX3 Abs were found in 11 (13.9%, 95% CI 7.2-23.5) women. Anti-PTX3 were slightly associated with gestational diabetes mellitus (GDM) (p=0.04) and resulted slightly associated with intra-uterine growth restriction (p=0.09)