The clinical and molecular cardiometabolic fingerprint of an exploratory psoriatic arthritis cohort is associated with the disease activity and differentially modulated by methotrexate and apremilast

Objectives: (1) To evaluate clinical and molecular cardiovascular disease (CVD) signs and their relationship with psoriatic arthritis (PsA) features and (2) to identify a clinical patient profile susceptible to benefit from methotrexate (MTX) and/or apremilast regarding CVD risk. Methods: This cross-sectional study included 100 patients with PsA and 100 age-matched healthy donors. In addition, an exploratory cohort of 45 biologically naïve patients treated for 6 months with apremilast, MTX or combined therapy according to routine clinical practice was recruited. Extensive clinical and metabolic profiles were obtained. Ninety-nine surrogate CVD-related molecules were analysed in plasma and peripheral blood mononuclear cells (PBMCs). Hard cluster analysis was performed to identify the clinical and molecular phenotypes. Mechanistic studies were performed on adipocytes. Results: Cardiometabolic comorbidities were associated with disease activity and long-term inflammatory status. Thirty-five CVD-related proteins were altered in the plasma and PBMCs of PsA patients and were associated with the key clinical features of the disease. Plasma levels of some of the CVD-related molecules might distinguish insulin-resistant patients (MMP-3, CD163, FABP-4), high disease activity (GAL-3 and FABP-4) and poor therapy outcomes (CD-163, LTBR and CNTN-1). Hard cluster analysis identified two phenotypes of patients according to the rates of cardiometabolic comorbidities with distinctive clinical and molecular responses to each treatment. Conclusions: (1) Novel CVD-related proteins associated with clinical features could be emerging therapeutic targets in the context of PsA and (2) the pleiotropic action of apremilast could make it an excellent choice for the management of PsA patients with high CVD risk, targeting metabolic alterations and CVD-related molecules

Pregnancy outcomes in a multidisciplinary unit of pregnant women with systemic autoimmune rheumatic diseases and hereditary thrombophilias

INTRODUCCIÓN Las enfermedades reumáticas autoinmunes sistémicas (ERAS) y las trombofilias hereditarias (TH) pueden estar asociadas a embarazos de alto riesgo obstétrico. El objetivo principal de este estudio consiste en describir los episodios de gestación atendidos en una consulta multidisciplinar (CM) de mujeres embarazadas con ERAS y TH primarias. METODOLOGÍA Estudio observacional retrospectivo basado en datos de rutina de práctica clínica registrados en una base de datos de mujeres embarazadas con ERAS y TH primarias atendidas en una CM y seguidas consecutivamente en el Hospital Universitario Virgen de las Nieves de Granada entre enero de 2012 y mayo de 2018. El análisis de las variables basales antes de la atención en la CM se realizó por mujeres (n = 143) y el de las variables de seguimiento por episodios de gestación (n = 198). Este estudio describe los resultados gestacionales exitosos con recién nacidos vivos, los resultados gestacionales adversos (abortos y muertes fetales), las complicaciones neonatales y las complicaciones maternas durante la atención en la CM. Los resultados gestacionales adversos durante la atención estándar (previa a la CM) fueron comparados con los registrados durante la CM. Para esta comparación se calculó la reducción absoluta del riesgo (RAR) y el número necesario de mujeres a tratar (NNT). RESULTADOS Se registraron 198 embarazos pertenecientes a 143 mujeres (112 con ERAS y 31 con TH primarias). Se registraron 191 (96.5%) resultados gestacionales exitosos y 7 (3.5%) resultados gestacionales adversos durante la CM (5 abortos y 2 muertes fetales). Los resultados durante la atención estándar previa a la CM mostraron que el 60.8% de las mujeres habían presentado más de un aborto espontáneo y el 4.2% alguna muerte fetal. En cambio, tras la atención en la CM, por cada 100 mujeres tratadas en la CM se registró un 57.3% menos de abortos espontáneos y un 2.8% menos de muertes fetales de las que se producirían si no hubieran sido tratadas en la CM, según la RAR, IC 95% [48.8-65.9] (p_valor < 0.001) e IC 95% [1.1-6.6] (p_valor = 0.289) respectivamente. El NNT para evitar un aborto espontáneo fue de 1.74; IC 95% [1.5-2.1] y para evitar una muerte fetal NNT = 35.75 IC 95% [15.2-90.9]. El 84.8% de los recién nacidos y el 93.3% de las mujeres no experimentaron complicaciones neonatales ni maternas durante la atención en la CM. CONCLUSIONES Este estudio pretende dar a conocer la alta tasa de resultados gestacionales exitosos, así como la reducción drástica de los resultados gestacionales adversos tras la atención en una CM integrada por reumatólogos, internistas, obstetras, hematólogos, nefrólogos, pediatras y/o neonatólogos. Resultados aún más significativos al tratarse de una población con un alto porcentaje de resultados gestacionales adversos durante la atención estándar, previa a la CM. Estos resultados podrían ser útiles para la promoción de las CM en el manejo de los embarazos de mujeres con ERAS y TH.INTRODUCTION Rheumatic diseases (RD) and hereditary thrombophilias (HT) can be associated with high-risk pregnancies. The main objective of this study is to describe the gestational episodes seen in a multidisciplinary consultation (MC) of pregnant women with RD and primary HT. METHODOLOGY Retrospective observational study based on clinical practice data. These ones were recorded in a database of pregnant women with RD and primary HT attended in a MC and consecutively followed up at the Hospital Universitario Virgen de las Nieves in Granada between January 2012 and May 2018. Analysis of baseline variables before MC can was performed by women (n=143) and analysis of follow-up variables by gestation episodes (n=198). This study describes successful gestational outcomes with newborns, adverse gestational outcomes (miscarriages and foetal deaths), neonatal complications and maternal complications during MC care. Adverse gestational outcomes during standard care (pre-MC) were compared with those recorded during MC. For this comparison, the absolute risk reduction (ARR) and the number of needed women to treat (NNT) were calculated. RESULTS A total of 198 pregnancies belonging to 143 women (112 with RD and 31 with HT). There were 191 (96.5%) successful gestational outcomes and 7 (3.5%) adverse gestational outcomes during MC (5 miscarriages and 2 foetal deaths). Results during standard care (pre-MC) showed that 60.8% of women had more than one miscarriage and 4.2% some foetal death. In contrast, after MC care, for every 100 women treated at MC, there were 57.3% fewer miscarriages and 2.8% fewer foetal death than would have occurred if they had not been treated at MC, according to the ARR, 95% CI [48.8-65.9] (p_value < 0.001) and 95% CI [1.1-6.6] (p_value = 0.289) respectively. The NNT to prevent miscarriage was 1.74; 95% CI [1.5-2.1] and to prevent foetal death NNT = 35.75 95% CI [15.2-90.9]. 84.8% of newborns and 93.3% of women did not experience any complication during the MC care. CONCLUSIONS This study aims to show the high rate of successful gestational outcomes, as well as the drastic reduction of adverse gestational outcomes after care in a MC integrated by rheumatologists, internists, obstetricians, hematologists, nephrologists, pediatricians and/or neonatologists. These results are even more significant in a population with a high percentage of adverse outcomes during standard care prior to the MC. These results could be useful for the promotion of MC in the management of pregnancies in women with RD and HT.Tesis Univ. Granada

Multidisciplinary Unit Improves Pregnancy Outcomes in Women with Rheumatic Diseases and Hereditary Thrombophilias: An Observational Study.

Rheumatic diseases (RD) and hereditary thrombophilias (HT) can be associated with high-risk pregnancies. This study describes obstetric outcomes after receiving medical care at a multidisciplinary consultation (MC) and compares adverse neonatal outcomes (ANOs) before and after medical care at an MC. This study is a retrospective observational study among pregnant women with RD and HT treated at an MC of a university hospital (southern Spain) from 2012 to 2018. Absolute risk reduction (ARR) and number needed to treat (NNT) were calculated. A total of 198 pregnancies were registered in 143 women (112 with RD, 31 with HT), with 191 (96.5%) pregnancies without ANOs and seven (3.5%) pregnancies with some ANOs (five miscarriages and two foetal deaths). Results previous to the MC showed 60.8% of women had more than one miscarriage, with 4.2% experiencing foetal death. MC reduced the ANO rate by AAR = 60.1% (95%CI: 51.6-68.7%). The NNT to avoid one miscarriage was 1.74 (95%CI: 1.5-2.1) and to avoid one foetal death NNT = 35.75 (95CI%: 15.2-90.9). A total of 84.8% of newborns and 93.2% of women did not experience any complication. As a conclusion, the follow-up of RD or HT pregnant women in the MC drastically reduced the risk of ANOs in this population with a previous high risk

Multidisciplinary Unit Improves Pregnancy Outcomes in Women with Rheumatic Diseases and Hereditary Thrombophilias: An Observational Study

Rheumatic diseases (RD) and hereditary thrombophilias (HT) can be associated with high-risk pregnancies. This study describes obstetric outcomes after receiving medical care at a multidisciplinary consultation (MC) and compares adverse neonatal outcomes (ANOs) before and after medical care at an MC. This study is a retrospective observational study among pregnant women with RD and HT treated at an MC of a university hospital (southern Spain) from 2012 to 2018. Absolute risk reduction (ARR) and number needed to treat (NNT) were calculated. A total of 198 pregnancies were registered in 143 women (112 with RD, 31 with HT), with 191 (96.5%) pregnancies without ANOs and seven (3.5%) pregnancies with some ANOs (five miscarriages and two foetal deaths). Results previous to the MC showed 60.8% of women had more than one miscarriage, with 4.2% experiencing foetal death. MC reduced the ANO rate by AAR = 60.1% (95%CI: 51.6−68.7%). The NNT to avoid one miscarriage was 1.74 (95%CI: 1.5–2.1) and to avoid one foetal death NNT = 35.75 (95CI%: 15.2–90.9). A total of 84.8% of newborns and 93.2% of women did not experience any complication. As a conclusion, the follow-up of RD or HT pregnant women in the MC drastically reduced the risk of ANOs in this population with a previous high risk

Predictors of Progression and Mortality in Patients with Prevalent Rheumatoid Arthritis and Interstitial Lung Disease: A Prospective Cohort Study

Objectives: To describe a prospective cohort of patients with rheumatoid arthritis associated with interstitial lung disease (RA-ILD) and identify risk factors associated with disease progression and mortality in this cohort. Patients and methods: We performed a multicenter, prospective, observational study of patients with RA-ILD receiving disease-modifying antirheumatic drugs (DMARDs) between 2015 and 2020. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline and at 60 months. The main endpoint was “Progression to ILD at the end of follow-up” in terms of the following outcomes: (1) improvement (i.e., improvement in forced vital capacity (FVC) ≥10% or diffusing capacity of the lungs for carbon monoxide (DLCO) ≥15% and absence of radiological progression); (2) nonprogression (stabilization or improvement in FVC ≤10% or diffusing capacity of the lungs for carbon monoxide (DLCO) 10% or DLCO >15% and radiological progression); or (4) death. We recorded demographic and clinical characteristics, lung function, and the incidence of adverse events. A Cox regression analysis was performed to identify factors associated with the worsening of ILD. Results: After 60 months, lung disease had stabilized in 66 patients (56.9%), improved in 9 (7.8%), and worsened in 23 (19.8%). Eighteen patients (15.5%) died, with a mean survival of 71.8 (1.9) months after diagnosis of ILD. The Cox multivariate analysis revealed the independent predictors of worsening of RA-ILD to be usual interstitial pneumonia (hazard ratio (HR), 2.6 (95%CI, 1.0–6.7)), FVC <80% (HR, 3.8 (95%CI, 1.5–6.7)), anticitrullinated protein antibody titers (HR, 2.8 (95%CI, 1.1–6.8)), smoking (HR, 2.5 (95%CI, 1.1–6.2)), and treatment with abatacept, tocilizumab, or rituximab (HR, 0.4 (95%CI, 0.2–0.8)). During follow-up, 79 patients (68%) experienced an adverse event, mostly infection (61%). Infection was fatal in 10/18 patients (55.5%) during follow-up. Conclusions: Lung function is stable in most patients with RA-ILD receiving treatment with disease-modifying anti-rheumatic drugs (DMARDs), although one-third worsened or died. Identifying factors associated with worsening in RA-ILD is important for clinical management.Grant for Medical Researchers of the “Fundación Española de Reumatología” 2019.Ye

Characteristics and Predictors of Progression Interstitial Lung Disease in Rheumatoid Arthritis Compared with Other Autoimmune Disease: A Retrospective Cohort Study

Objectives: To describe the characteristics and progression of interstitial lung disease in patients with associated systemic autoimmune disease (ILD-SAI) and to identify factors associated with progression and mortality. Patients and methods: We performed a multicenter, retrospective, observational study of patients with ILD-SAI followed between 2015 and 2020. We collected clinical data and performed pulmonary function testing and high-resolution computed tomography at diagnosis and at the final visit. The main outcome measure at the end of follow-up was forced vital capacity (FVC) >10% or diffusing capacity of the lungs for carbon monoxide >15% and radiological progression or death. Cox regression analysis was performed to identify factors associated with worsening of ILD. Results: We included 204 patients with ILD-SAI: 123 (60.3%) had rheumatoid arthritis (RA), 58 had (28.4%) systemic sclerosis, and 23 (11.3%) had inflammatory myopathy. After a median (IQR) period of 56 (29.8–93.3) months, lung disease had stabilized in 98 patients (48%), improved in 33 (16.1%), and worsened in 44 (21.5%). A total of 29 patients (14.2%) died. Progression and hospitalization were more frequent in patients with RA (p = 0.010). The multivariate analysis showed the independent predictors for worsening of ILD-SAI to be RA (HR, 1.9 [95% CI, 1.3–2.7]), usual interstitial pneumonia pattern (HR, 1.7 [95% CI, 1.0–2.9]), FVC (%) (HR, 2.3 [95% CI, 1.4–3.9]), and smoking (HR, 2.7 [95%CI, 1.6–4.7]). Conclusion: Disease stabilizes or improves after a median of 5 years in more than half of patients with ILD-SAI, although more than one-third die. Data on subgroups and risk factors could help us to predict poorer outcomes.Ye

Importance of Vaccination against SARS-CoV-2 in Patients with Interstitial Lung Disease Associated with Systemic Autoimmune Disease.

Objectives: To describe the frequency of COVID-19 and the effect of vaccination in patients with interstitial lung disease and systemic autoimmune disease (ILD-SAD) and to identify factors associated with infection and severity of COVID-19. Methods: We performed a cross-sectional multicenter study of patients with ILD-SAD followed between June and October 2021. The main variable was COVID-19 infection confirmed by a positive polymerase chain reaction (PCR) result for SARS-CoV-2. The secondary variables included severity of COVID-19, if the patient had to be admitted to hospital or died of the disease, and vaccination status. Other variables included clinical and treatment characteristics, pulmonary function and high-resolution computed tomography. Two logistic regression was performed to explore factors associated with “COVID-19” and “severe COVID-19”. Results: We included 176 patients with ILD-SAD: 105 (59.7%) had rheumatoid arthritis, 49 (27.8%) systemic sclerosis, and 22 (12.54%) inflammatory myopathies. We recorded 22/179 (12.5%) SARS-CoV-2 infections, 7/22 (31.8%) of them were severe and 3/22 (13.22%) died. As to the vaccination, 163/176 (92.6%) patients received the complete doses. The factors associated with SARS-CoV-2 infection were FVC (OR (95% CI), 0.971 (0.946−0.989); p = 0.040), vaccination (OR (95% CI), 0.169 (0.030−0.570); p = 0.004), and rituximab (OR (95% CI), 3.490 (1.129−6.100); p = 0.029). The factors associated with severe COVID-19 were the protective effect of the vaccine (OR (95% CI), 0.024 (0.004−0.170);

Safety and Effectiveness of Abatacept in a Prospective Cohort of Patients with Rheumatoid Arthritis-Associated Interstitial Lung Disease.

To prospectively evaluate the safety and efficacy profile of abatacept in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). We performed a prospective observational multicenter study of a cohort of patients with RA-ILD treated with abatacept between 2015 and 2021. Patients were evaluated using high-resolution computed tomography and pulmonary function tests at initiation, 12 months, and the end of follow-up. The effectiveness of abatacept was evaluated based on whether ILD improved, stabilized, progressed, or was fatal. We also evaluated factors such as infection, hospitalization, and inflammatory activity using the 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR). Cox regression analysis was performed to identify factors associated with progression of lung disease. The study population comprised 57 patients with RA-ILD treated with abatacept for a median (IQR) of 27.3 (12.2-42.8) months. Lung disease had progressed before starting abatacept in 45.6% of patients. At the end of follow-up, lung disease had improved or stabilized in 41 patients (71.9%) and worsened in 13 (22.8%); 3 patients (5.3%) died. No significant decreases were observed in forced vital capacity (FVC) or in the diffusing capacity of the lung for carbon monoxide (DLCO).The factors associated with progression of RA-ILD were baseline DAS28-ESR (OR [95% CI], 2.52 [1.03-3.12]; p = 0.041), FVC (OR [95% CI], 0.82 [0.70-0.96]; p = 0.019), and DLCO (OR [95% CI], 0.83 [0.72-0.96]; p = 0.018). Only 10.5% of patients experienced severe adverse effects. Pulmonary function and joint inflammation stabilized in 71% of patients with RA-ILD treated with abatacept. Abatacept had a favorable safety profile