Papers by Ana Maria Gheorghiu
FARMACIA
Peripheral vasculopathy is a severe complication of systemic sclerosis (SSc) through digital ulce... more Peripheral vasculopathy is a severe complication of systemic sclerosis (SSc) through digital ulcerations (DUs) that can lead to gangrene or amputations. Bosentan, an antagonist of endothelin receptor 1 with proven efficacy in preventing new onset of DUs in patients with SSc, was first introduced in Romania in 2014. Our objective was to evaluate the efficacy and long-term safety of bosentan in SSc patients in a prescribing centre in Bucharest. We included 49 patients with SSc (39 women, with a median (IQR) duration of follow-up of 25 (43) months), evaluated in our clinic between November 2014 and March 2021, who presented with DUs on admission or in the preceding three months. We compared clinical and laboratory data, including the number of DUs, Visual Analogue Scale (VAS) for Raynaud's phenomenon and DUs, Health Assessment Questionnaire disease index (HAQ) at baseline and follow-up. At the initiation of treatment, patients presented a median (IQR) of 4 (4) DUs, VAS Raynaud 8 (2), VAS DUs 9 (3), HAQ 1.75 (1), with a significant reduction at 12 months of the number of DUs to DUs 0 (0), VAS Raynaud 2 (2.9), VAS DUs 0.5 (1.75) and HAQ 0.88 (1.13), with a maintained efficacy for DUs, VAS Raynaud and VAS DUs for the entire follow-up period. There were 8 (16.3%) cases of hepatic cytolysis 3-6 times the upper normal limit which required discontinuation of treatment, but otherwise no severe reactions. The treatment with bosentan was efficient on the long-term and well-tolerated by most patients. Rezumat Afectarea vasculară periferică este o complicație severă a sclerodermiei sistemice (ScS), prin ulcerațiile digitale (UD) care pot duce la gangrenă sau amputații. Bosentanul, antagonist al receptorilor endotelinei, cu eficiență dovedită în prevenția apariției UD la pacienții cu ScS, a fost introdus în România în 2014. Obiectivul studiului a fost de a evalua eficacitatea și siguranța pe termen lung a tratamentului cu bosentan la pacienții cu ScS dintr-un centru prescriptor din București. Au fost incluși în studiu 49 de pacienți cu ScS (39 femei, cu durata mediană (IQR) de urmărire 25 (43) luni) în perioada noiembrie 2014martie 2021, care au avut UD la prezentare sau în ultimele 3 luni anterior. S-au comparat datele clinice și de laborator (inclusiv numărul de UD, Visual Analogue Scale (VAS) pentru fenomenul Raynaud și UD, Health Assessment Questionaire index (HAQ) de la inițierea terapiei până la 6 ani de urmărire. La inițiere, pacienții au prezentat 4 (4) UD, VAS Raynaud 8 (2), VAS UD 9 (3), HAQ 1,75 (1,0), cu scăderea semnificativă la 12 luni a numărului de UD la UD 0 (0), VAS Raynaud 2 (2,9), VAS UD 0,5 (1,75) și HAQ 0,88 (1,13), p < 0,001 pentru toate, cu menținerea eficacității pentru UD, VAS Raynaud și VAS UD pentru întreaga perioadă de urmărire. S-au înregistrat 8 (16,3%) sindroame de citoliză hepatică 3-6 x LSN, care au necesitat oprirea tratamentului, în rest nu a fost înregistrată nicio reacție adversă severă. Tratamentul cu bosentan a avut eficiență îndelungată și toleranță bună la majoritatea pacienților.
Annals of the Rheumatic Diseases, 2020
Background: Patient reported outcome measures (PROM) are important for clinical practice and rese... more Background: Patient reported outcome measures (PROM) are important for clinical practice and research. Given the unmet need for a comprehensive PROM for systemic sclerosis (SSc), the ScleroID questionnaire was developed by a joint team of patients with SSc and medical experts. This is intended as a brief, specific, patient-derived, disease impact score for research and clinical use in SSc. Objectives: Here, we present the validation and final version of the ScleroID. Methods: This EULAR-endorsed project involves 9 European expert SSc centers. Patients fulfilling the ACR/EULAR 2013 criteria were prospectively included since 05/16 in a large observational cohort study. Patients completed the ScleroID and comparators SHAQ, EQ5D, SF36. They also weighted the 10 dimensions of the ScleroID by distributing 100 points according to the perceived impact on their health. The final score calculation is based on the ranking of the weights. The validation study included a reliability arm and a longitudinal arm, looking at sensitivity to change at follow-up. Results: Of the 472 patients included at baseline, 109 patients also had a reliability visit and 113 patients a follow-up visit. 84.5% of patients were female, 29.8% had diffuse SSc, mean age was 54.6 years, and mean disease duration 9.5 years. The highest weights were assigned by the patients to Raynaud`s phenomenon, fatigue, hand function and pain, confirming our previous results. The total ScleroID score showed good Spearman correlation coefficients with the comparators (SHAQ, 0.73; EQ5D-0.48; Patient's global assessment, VAS 0.77; HAQ-DI 0.62; SF36 physical score-0.62; each p<0.001). The internal consistency was good: Crohnbach's alpha 0.866, similar to SS-HAQ (0.88) and higher than EQ5D (0.77). The ScleroID had a very good reliability: intra-class correlation coefficient 0.839 (ranging 0.608 to 0.788 for the individual items), superior to all comparators. Twenty of 113 patients reported a change in their disease status at follow up. Sensitivity to change: the standardized response mean was 0.34 for the total ScleroID score and highest for lower GI (0.633) and life choices domains (0.521), superior to all other PROM. Figure 1 shows the final ScleroID. Figure 1. Conclusion: The EULAR ScleroID is a novel PROM designed for use in clinical practice and clinical trials to reflect the disease impact of SSc, showing good performance in the validation study. Importantly, Raynaud syndrome, impaired hand function, pain and fatigue were the main patient reported drivers of disease impact.
Rheumatology
Objective Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in syst... more Objective Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in systemic sclerosis (SSc) patients. We aimed to investigate the impact of sex on SSc-ILD. Methods EUSTAR SSc patients with radiologically confirmed ILD and available percentage predicted forced vital capacity (%pFVC) were included. Demographics and disease features were recorded. A change in %pFVC over 12 months (s.d. 6) (cohort 1) was classified into stable (≤4%), mild (5–9%) and large progression (≥10%). In those with 2-year longitudinal %pFVC (cohort 2), the %pFVC change at each 12-month (s.d. 6) interval was calculated. Logistic regression analyses [odds ratio (OR) and 95% CI] and Cox proportional hazards models adjusted for age and %pFVC were applied. Results A total of 1136 male and 5253 female SSc-ILD patients were identified. Males were significantly younger, had a shorter disease duration, had a higher prevalence of CRP elevation and frequently had diffuse cutaneous involvement. In c...
Diagnostics
Background: The recently published 2019 American College of Rheumatology/European Alliance of Ass... more Background: The recently published 2019 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria for systemic lupus erythematosus (SLE) were developed to increase the reliability and identification of SLE, especially in early disease. With the emergence of several new drugs for SLE, identifying and treating patients early are more important than ever. Methods: Data of 446 SLE patients evaluated in our center between 1996–2019 and 226 controls with other autoimmune diseases evaluated between 2001–2022 were retrospectively analyzed. The sensitivity and specificity of the 2019 ACR/EULAR criteria were compared to the 2012 SLICC and the 1997 ACR criteria. Results: The 2019 ACR/EULAR criteria showed very good sensitivity (86.6%) compared to the 1997 ACR criteria (76.7%), p < 0.001, with a trend toward significance compared to the 2012 SLICC criteria (83.6%), p = 0.072. Their sensitivity remained high (87.6%) in patients wit...
RMD Open
ObjectivesTocilizumab showed trends for improving skin fibrosis and prevented progression of lung... more ObjectivesTocilizumab showed trends for improving skin fibrosis and prevented progression of lung fibrosis in systemic sclerosis (SSc) in randomised controlled clinical trials. We aimed to assess safety and effectiveness of tocilizumab in a real-life setting using the European Scleroderma Trial and Research (EUSTAR) database.MethodsPatients with SSc fulfilling the American College of Rheumatology (ACR)/EULAR 2013 classification criteria, with baseline and follow-up visits at 12±3 months, receiving tocilizumab or standard of care as the control group, were selected. Propensity score matching was applied. Primary endpoints were the modified Rodnan skin score (mRSS) and FVC at 12±3 months compared between the groups. Secondary endpoints were the percentage of progressive/regressive patients for skin and lung at 12±3 months.ResultsNinety-three patients with SSc treated with tocilizumab and 3180 patients with SSc with standard of care fulfilled the inclusion criteria. Comparison between ...
Rheumatology
Objectives To estimate the prevalence of long-term exposure to glucocorticoids (GCs) and to ident... more Objectives To estimate the prevalence of long-term exposure to glucocorticoids (GCs) and to identify factors associated with, and variations in prescribing practices over time and across recruiting countries. Methods We included patients with SSc having a visit recorded in the EUSTAR database from January 2013 onward. We analysed the prevalence and the main features of GCs users, their exposure to GCs over time, and their GCs dosages. Multivariable linear regression was used to analyse the factors identified as associated with GCs intake duration. Time trends, and variations in GCs utilization across recruiting countries were explored. Missing data were imputed using multiple imputation with chained equations. Results The 9819 patients included were mostly females (85%), the majority had lcSSc (73%), and the median age was 58 years. At baseline, 34% of patients (n = 2769/8109) (48% dcSSc vs 29% lcSSc) were on GCs, and the median dose was 7.5 mg/day. GCs users were more frequently ma...
Rheumatology
Objective To develop and validate the prognostic prediction model DU-VASC to assist the clinician... more Objective To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor. Methods We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors. Results Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in ...
Annals of the Rheumatic Diseases, 2021
Background:In SSc, ILD is a major cause of morbidity and mortality. High resolution computed tomo... more Background:In SSc, ILD is a major cause of morbidity and mortality. High resolution computed tomography (HRCT) is the gold standard for the diagnosis. Predictors of ILD onset are eagerly awaited to improve SSc-ILD management. Pulmonary function test (PFTs) are routinely performed to measure lung function changes.Objectives:Our aim was to investigate the performance of DLCO (diffusing capacity of lung carbon monoxide) and FVC (forced vital capacity) in predicting the development of SSc-ILD.Methods:The longitudinal data of DLCO, FVC and ILD on HRCT of SSc patients from the EUSTAR database were evaluated at baseline (t0), after 12 (±4) (t1) and 24 (±4) (t2) months. Patients with negative HRCT for any sign of ILD both at t0 and t1 were included. Patients who presented or developed pulmonary hypertension during the study period were excluded. At baseline, demographic data, disease duration from Raynaud’s onset, disease subsets, autoantibodies and other laboratory and instrumental data we...
Rheumatology, 2022
Objectives To characterize patients with positive anti-topoisomerase I (ATA) in lcSSc. Methods SS... more Objectives To characterize patients with positive anti-topoisomerase I (ATA) in lcSSc. Methods SSc patients enrolled in the EUSTAR cohort with a disease duration of ≤3 years at database entry were considered. We assessed the risk of major organ involvement in the following groups: ATA-lcSSc vs ACA-lcSSc and vs ANA without specificity (ANA)-lcSSc, and ATA-lcSSc vs ATA-dcSSc. Cox regression models with time-dependent covariates were performed with the following outcomes: new-onset interstitial lung disease (ILD), ILD progression [forced vital capacity (FVC) decline ≥10% and ≥5% vs values at ILD diagnosis), primary myocardial involvement (PMI), pulmonary hypertension (PH), any organ involvement and all-cause mortality. Results We included 1252 patients [194 ATA-lcSSc (15.5%)], with 7.7 years (s.d. 3.5) of follow-up. ILD risk was higher in ATA-lcSSc vs ACA- and ANA-lcSSc and similar to ATA-dcSSc, although with less frequent restrictive lung disease. The risk of FVC decline ≥10% (35% of ...
Revista română de reumatologie, Jun 30, 2017
Background. Systemic sclerosis (SSc) is a complex chronic autoimmune disease, with an unpredictab... more Background. Systemic sclerosis (SSc) is a complex chronic autoimmune disease, with an unpredictable evolution and high morbidity and mortality rates. Objective. Evaluation of long-term survival and identification of prognostic factors in patients with systemic sclerosis. Methods. All patients with SSc of the EUSTAR100 center, having at least one visit between 2004 and 2016, were included. Data were analyzed for survival, cause of death, as well as for the following events defining disease worsening: increase in modified Rodnan score (mRSS) with at least 25% and 5 points (compared to baseline visit), decrease with at least 10% (compared to baseline) of predicted forced vital capacity (FVC) and predicted diffusing capacity of the lungs for carbon monoxide (DLCO), and presence of new digital ulcers (DUs). Logistic regression (LR), Cox proportional hazards regression and Kaplan-Meier survival curves were used in univariate and multivariate analysis to study survival and identify prognostic factors. Results. 137 patients were included in the study (89.1% females, mean age ± SD 56.7 ± 12.6 years, disease duration 9.7 ± 7.1 years), with a follow-up duration of up to 19 years. 96 patients had at least one follow-up visit and 66 (not including patients who died earlier than 2 years after the first presentation) had follow-up data at 2 years (± 6 months) after the first visit in the clinic. There were 19 reported deaths (13.9%), 11 attributed to SSc (of whom 8 were due to lung involvement). Risk factors for death were diffuse cutaneous subset and mRSS>14 at baseline (identified by LR adjusted for age and sex), male sex and proteinuria (Cox analysis). While in over half of the patients FVC and mRSS were stable or improved (86% and 96% respectively), and no new DUs occurred (64%), 52% of the patients presented significant worsening of DLCO during the entire followup. Risk factors for DLCO worsening at 2 years, by LR adjusted for sex and age, were male sex and diffuse cutaneous subset, while Cox analysis identified only male sex. The only risk factor identified for appearance of new DUs was the history of DUs at the first presentation. Conclusions. SSc often presents an unfavorable disease course, particularly due to lung involvement. Risk factors for disease worsening were male sex, diffuse cutaneous subset, and mRSS>14 at baseline. SSc-related deaths were mainly due to lung involvement, thus underlining the necessity of identifying predictive factors for lung function deterioration at the first presentation.
Romanian Journal of Rheumatology, Sep 30, 2017
Background. Lung involvement is the main disease related death cause in patients with systemic sc... more Background. Lung involvement is the main disease related death cause in patients with systemic sclerosis (SSc). The most frequent lung manifestations in SSc are interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). Objectives. Evaluation of lung involvement in patients with SSc and identification of predictive factors for severe lung involvement. Patients and methods. All patients with SSc of the EUSTAR100 center, having at least two visits between 2004 and 2016, were included. Survival status, cause of death, dyspnea, ILD on thorax radiography or high resonance thorax computer tomography (HRCT) and lung function tests were recorded during the entire follow-up. Severe lung involvement was defined as severe or end-stage lung involvement on the Medsger severity scale at any time during follow-up, or death. Cox proportional hazards regression was used in univariate and multivariate analysis to identify prognostic factors. Results. 89 patients were included (12.4% males, mean age±SD 49.2±12.2 years, disease duration 4.1±7.5 years), with a follow-up duration up to 13 years. 14 deaths were reported, half due to lung involvement (4 deaths due to ILD, 3 deaths due to PAH). Pulmonary involvement was identified in a large proportion: at first visit 28/55 present ILD on thorax radiography, 7/12 on HRCT scans; at the most recent visit 41/71 present ILD on X-ray, 18/24 on HRCT scans. At least 10% decrease of pulmonary diffusion capacity for carbon monoxyde (DLCO) and of forced vital capacity (FVC) was observed in 18/32 and 8/35 respectively; 24/48 developed severe or end-stage pulmonary involvement on the Medsger scale or have died. Risk factors for severe lung involvement were age>60 years, disease duration<3 years and diffuse cutaneous subset. Conclusion. SSc often presents unfavourable disease course, mostly due to pulmonary involvement. While half of the deaths reported were due to lung involvement, only about half of the patients presenting ILD-typical findings on Rx develop end-stage lung involvement or death. It is of great importance to screen at baseline for ILD and PAH, following up annually, even while patients are asymptomatic.
Rheumatology, 2021
Objective Digital pitting scars (DPS) are frequent, but little studied in SSc to date. Methods An... more Objective Digital pitting scars (DPS) are frequent, but little studied in SSc to date. Methods An analysis of SSc patients enrolled in the EUSTAR database. Primary objectives were to (i) examine DPS prevalence; (ii) examine whether DPS are associated with digital ulcers (DUs) and active digital ischaemia (DUs or gangrene); and (iii) describe other associations with DPS including internal organ complications. Secondary objectives were whether DPS are associated with (i) functional impairment; (ii) structural microvascular disease; and (iii) mortality. Descriptive statistics and parametric/non-parametric tests were used. Binary logistic regression was used to examine the association between DPS and DUs, active digital ischaemia and mortality. Results A total of 9671 patients were included with reported DPS at any time point (n = 4924) or ‘never’ DPS (n = 4747). The majority (86.9%) were female and mean age was 55.7 years. DPS were associated with longer disease and Raynaud’s duration ...
Annals of the Rheumatic Diseases, 2021
Background:Tocilizumab (TCZ) showed trends for improving skin fibrosis and prevented progression ... more Background:Tocilizumab (TCZ) showed trends for improving skin fibrosis and prevented progression of lung fibrosis in patients with systemic sclerosis (SSc) in placebo-controlled randomised clinical trials (RCTs). However, safety and effectiveness of TCZ beyond these selected and enriched clinical trial populations in SSc is still unknown.Objectives:To assess safety and effectiveness of TCZ treatment compared to standard of care in SSc patients from the large, multicentre, observational, real-life EUSTAR network/database using propensity score matching.Methods:SSc patients from the EUSTAR network/database, who fulfilled the ACR/EULAR 2013 classification criteria, with a baseline and a follow-up visit at 12±3 months, receiving TCZ or standard of care (controls), were selected. The following variables were used for the propensity score matching (1:1): age at diagnosis, gender, disease subtype, baseline modified Rodnan skin score (mRSS), forced vital capacity (FVC), and diffusing capaci...
Annals of the Rheumatic Diseases, 2020
Background:Systemic lupus erythematosus (SLE) is a heterogenous autoimmune disease, with increase... more Background:Systemic lupus erythematosus (SLE) is a heterogenous autoimmune disease, with increased morbidity and mortality, often diagnosed in advanced stages. The recently published 2019 American College Of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for SLE are weighted, hierarchically clustered criteria developed to increase reliability and the identification of early SLE.Objectives:To compare the sensitivity and specificity of the 2019 ACR/EULAR criteria with the 2012 SLICC criteria in a large single-centre cohort of patients with SLE, diagnosed according to expert oppinion.Methods:Data of SLE patients evaluated in our centre between 1996-2019 have been retrospectively analyzed. The control cohort included patients with positive antinuclear antibodies of other ethiology than SLE, evaluated between 2001-2019. The sensitivity and specificity of the 2019 ACR/EULAR and 2012 SLICC criteria were tested using the McNemar test for correlated propo...
FRIDAY, 15 JUNE 2018, 2018
on behalf of the EULAR study group on microcirculation in Rheumatic diseases.
THURSDAY, 14 JUNE 2018, 2018
was estimated using a generalised estimating equation extension of multivariate Poisson regressio... more was estimated using a generalised estimating equation extension of multivariate Poisson regression models. Results: We identified 81 568 incident cases of PsO/PsA (mean age 48.5 years [SD 17.8], 51.5% female). Individuals with PsO/PsA were at significantly higher risk of being diagnosed with 8/41 types of cancer examined, including eye and orbit (4 fold), female genital (3 fold), non-melanoma skin (2 fold), prostate (males; 1.1 fold) (table 1). Incidence of rectal and colon cancer was lower among PsO/ PsA pts relative to the non-PsO/PsA cohort (table 1).
Scleroderma, myositis and related syndromes, 2018
Background: Patient reported outcome measures (PROs) are increasingly important for clinical prac... more Background: Patient reported outcome measures (PROs) are increasingly important for clinical practice and research. Given the unmet need for a comprehensive PRO for systemic sclerosis (SSc), the ScleroID questionnaire was developed by a joint team of patients with SSc and medical experts in the field. This approach was designed as a brief, specific, patient-derived, disease impact score for research and clinical use in SSc. A preliminary analysis was previously reported. Here, we present the first computation of the ScleroID score and an extended pre-final analysis from the ongoing ScleroID validation study. Methods: This EULAR-endorsed project involves 11 European expert SSc centres. Patients fulfilling the ACR/EULAR 2013 criteria were prospectively included since 05/16 in the ongoing observational cohort study. Patients completed the ScleroID questionnaire (figure 1), as well as the selected comparators mSHAQ, EQ5D, and SF36. Additionally, they weighted the 10 dimensions of the ScleroID by distributing 100 points according to the perceived impact on their health. The final score calculation was based on the ranking of the weights. The study included a reliability arm (follow-up questionnaire 7-10 days from baseline), as well as a longitudinal arm, looking at sensitivity to change at follow-up visits after 6 and 12 months from baseline.
THURSDAY, 14 JUNE 2018:, 2018
Annals of the Rheumatic Diseases, 2016
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Papers by Ana Maria Gheorghiu