Objective
To determine mortality and causes of death in a multinational inception cohort of subjects with systemic sclerosis (SSc).
Methods
We quantified mortality as standardized mortality ratio ...(SMR), years of life lost, and percentage mortality in the first decade of disease. The inception cohort comprised subjects recruited within 4 years of disease onset. For comparison, we used a prevalent cohort, which included all subjects irrespective of disease duration at recruitment. We determined a single primary cause of death (SSc related or non–SSc related) using a standardized case report form, and we evaluated predictors of mortality using multivariable Cox regression.
Results
In the inception cohort of 1,070 subjects, there were 140 deaths (13%) over a median follow‐up of 3.0 years (interquartile range 1.0–5.1 years), with a pooled SMR of 4.06 (95% confidence interval 95% CI 3.39–4.85), up to 22.4 years of life lost in women and up to 26.0 years of life lost in men, and mortality in the diffuse disease subtype of 24.2% at 8 years. In the prevalent cohort of 3,218 subjects, the pooled SMR was lower at 3.39 (95% CI 3.06–3.71). In the inception cohort, 62.1% of the primary causes of death were SSc related. Malignancy, sepsis, cerebrovascular disease, and ischemic heart disease were the most common non–SSc‐related causes of death. Predictors of early mortality included male sex, older age at disease onset, diffuse disease subtype, pulmonary arterial hypertension, and renal crisis.
Conclusion
Early mortality in SSc is substantial, and prevalent cohorts underestimate mortality in SSc by failing to capture early deaths, particularly in men and those with diffuse disease.
Dual targeted therapy (DTT) has emerged as a promising approach in patients with refractory spondyloarthritis (SpA) or psoriatic arthritis (PsA) and extra-musculoskeletal manifestations of both ...diseases, but its effectiveness/safety ratio still remains unclear. This is a retrospective, real-world multicenter study in refractory SpA and PsA patients with simultaneous use of two biological or synthetic targeted agents. Effectiveness was assessed using Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) and Disease Activity in Psoriatic Arthritis (DAPSA) Score. We identified 39 different DTT combinations in 36 patients (22 SpA; 14 PsA), 25 of them with concomitant inflammatory bowel disease. The most commonly used combinations were TNF inhibitor plus antagonist of the IL12/23 pathway, followed by TNF inhibitor plus IL-17 antagonist. During a median exposure of 14.86 months (IQR 8-20.2), DTT retention rate was 69.4% (n=25/36; 19 SpA, 6 PsA). Major clinical improvement (change in ASDAS-CRP > 2 or improvement > 85% in DAPSA) was achieved in 69.4% of patients (n=25/36 therapeutical combinations; 17/21 SpA, 8/15 PsA), with a 58.3% (n=21/36 combinations; 15/20 SpA, 6/13 PsA) low-activity/remission rate. Of the patients who were receiving glucocorticoids, 55% managed to withdraw them during follow-up. Interestingly, only four serious adverse events in three patients were observed, leading to DTT discontinuation.
Abstract Objective To validate the 2013 ACR/EULAR classification criteria for systemic sclerosis (SSc) in patients from a capillaroscopy clinic. Methods All patients attended in a capillaroscopy ...clinic were included. Sociodemographic and SSc related variables were collected. Using as gold standard for SSc the clinical judgement, the performance (sensitivity, specificity, predictive values, likelihood ratios) of the 2013 ACR/EULAR criteria were analysed. Receiver operating characteristic (ROC) curve and the area under the curve (AUC) were calculated for the global score and individual items, and the best cut-offs were obtained. Results We included 327 patients (84% women, mean age at capillaroscopy 48 years). Main reasons for capillaroscopy referral were Raynaud′s phenomenon (39%) and SSc evaluation (27%). The most frequent final clinical diagnosis were SSc (32.4%) and primary Raynaud′s phenomenon (25.7%). The 2013 ACR/EULAR SSc classification criteria were met by 116 patients (35.5%). Sensitivity and specificity of the new criteria were 98.1% and 94.6%, respectively, and positive and negative predictive values were 89.7% and 99.1%. The individual variables with the best sensitivity were Raynaud′s phenomenon (99.1%) and abnormal nailfold capillaries (81.1%). All the individual variables, except Raynaud′s phenomenon, puffy fingers and sclerodactily showed high specificity values, over 90%. The best cut-offs of the total score were ≥8, ≥9 and ≥10, and the AUC=0.993. Conclusions We validated the new ACR/EULAR classification criteria for SSc in unselected patients from a capillaroscopy clinic. Global score and individual items included in the new criteria show high diagnostic accuracy and discriminatory capacity.
Objective To analyze the causes of death, survival, and risk factors for mortality in a large series of Spanish systemic sclerosis (SSc) patients followed over the last 25 years in a tertiary care ...university hospital. Methods Demographic, clinical, and outcome data from all SSc patients followed in the rheumatology department were included in a database created in 1989. ANOVA, Kruskal-Wallis, or χ2 tests were used to identify differences among groups; Kaplan-Meier analysis was used to estimate survival, and Cox proportional hazards regression analysis was used to identify factors associated with mortality. Results A total of 204 patients were included, of whom 182 (89%) were women. Mean age at diagnosis was 49 ± 17 years, and mean follow-up was 8 years. Over 1635 patient-years, 36 of 44 deaths were attributable to SSc: 28 related to cardiorespiratory involvement, 4 to peripheral vascular disease, 3 to gastrointestinal, and 1 to renal involvement. The main SSc-unrelated causes of death were malignancy (3 cases) and infections (2 cases). Survival rates from disease onset were 85, 75, and 55% at 5, 10, and 20 years, respectively, with poorer survival in patients with renal disease and pulmonary hypertension (PH). Independent prognostic factors for mortality were older age at diagnosis, diffuse skin involvement, proteinuria, PH, and elevated erythrocyte sedimentation rate. Conclusions Ten-year survival is over 70% in Spanish SSc patients. The main causes of death are lung and cardiac involvement, and to a lesser extent, peripheral vascular disease and coexisting malignancy. Diffuse subset, proteinuria, PH, elevated erythrocyte sedimentation rate and older age at diagnosis are the main risk factors for mortality.
To analyze the performance of the 1980 ACR and new 2013 ACR/EULAR criteria for systemic sclerosis (SSc) in cutaneous SSc (lcSSc) patients, especially those affected by lcSSc and pulmonary arterial ...hypertension (PAH).
All patients with a clinical lcSSc diagnosis from a prospective observational SSc cohort were included. Sociodemographic and disease-related variables were collected, and PAH confirmed by right heart catheterization (RHC). Performance of the 2013 and 1980 SSc criteria was analyzed in terms of clinical diagnosis. Descriptive and between-group analyses were performed as to the fulfillment of criterion sets, including comparison of survival.
Overall, 321 patients were included, 63% of whom fulfilled the 1980 ACR and 93% the 2013 ACR/EULAR criteria. Agreement between both criteria sets proved poor (κ = 0.23). LcSSC patients fulfilling both criterion sets were significantly younger at diagnosis, whilst presenting organ involvement, calcinosis, fingertip digital ulcers, and pitting scars more frequently than those who met the 2013 criteria only. Patients who fulfilled the 2013 but not the 1980 criteria presented a higher degree of ACA positivity and PAH. Nearly 12% of patients developed PAH. Patients who did not meet the 1980 criteria were affected by a milder disease from but demonstrated higher pulmonary vascular resistance and lower cardiac index than those fulfilling both criterion sets. Whereas patients with PAH met the 2013 criteria, only 47% fulfilled the 1980 criteria. Regardless of criterion set fulfillment, high mortality was observed in PAH patients, with no significant between-patient difference based on criterion set.
The new 2013 ARC/EULAR criteria prove more accurate than the former 1980 ACR criteria in identifying and differentiating patients with lcSSc, especially those with associated PAH. Since PAH exhibits a better prognosis if treated early, all SSc patients should undergo PAH screening.
This study reviewed the medical records of patients from the REMICAM cohort, a multicentric longitudinal study carried out in patients with IIM, followed up between 1980 and 2014 in 12 hospitals in ...Madrid, Spain. Patients with definite or probable JPM, JDM, adult DM, and adult PM according to the modified Bohan and Peter criteria were selected. We compared the characteristics between JDM and JPM, and between JIIM and adult IIM.
Eighty-six juvenile patients (75 JDMs and 11 JPMs) and 283 adult patients (133 DMs and 150 PMs) were included. Compared with patients with JDM, patients with JPM were older at diagnosis, had more fever and arthritis, and were less frequently treated with disease-modifying antirheumatic drugs (these differences were not statistically significant). Compared with patients with adult DM, those with JDM presented more frequently with calcinosis (33.8% vs 6.9%, p < 0.0001) and had less severe infections (4.3% vs 23.4%, p < 0.0001), malignancies (1.3% vs 25.6%, p < 0.0001), and mortality (3.5% vs 33%, p < 0.0001). Patients with JDM were treated less frequently with azathioprine (10.8% vs 44.7%, p < 0.0001).
Our findings confirm that JIIMs are a heterogeneous group of diseases with relevant differences compared with adult IIMs.
Objective
To evaluate the validity of different spondyloarthritis (SpA) features included in the Berlin diagnostic algorithm and the Assessment of SpondyloArthritis international Society (ASAS) ...classification criteria in an early SpA cohort.
Methods
This was a longitudinal multicenter study including patients from the ESPeranza program cohort who were suspected to have SpA. Subjects were ≤45 years old, and SpA symptom duration was 3–24 months. Patients with axial SpA symptoms were selected and categorized according to diagnosis (yes/no) of axial SpA. Descriptive analysis was performed, and the sensitivity, specificity, predictive value, and likelihood ratio (LR) of each feature were calculated.
Results
Of 775 patients suspected to have SpA, 665 had predominantly axial symptoms and 516 of these patients were diagnosed with axial SpA. The most useful SpA features were sacroiliitis on magnetic resonance imaging (positive LR 6.6) or radiograph (positive LR 31.1) and peripheral arthritis (positive LR 8.9). The features with the lowest diagnostic utility were a family history of SpA (positive LR 1.5) and good response to nonsteroidal antiinflammatory drugs (positive LR 1.6). Inflammatory back pain (IBP; according to ASAS criteria) was described in only 27% of SpA patients, with a positive LR of 2.3. HLA–B27 positivity was present in 245 (48%), and the positive LR was 2.8.
Conclusion
The diagnostic value of SpA features in patients with early axial SpA seems to be different than in patients with longstanding disease. Chronic back pain is better than IBP as an entry point to the diagnostic algorithm. Sacroiliitis on imaging is very important for early diagnosis, while the use of HLA–B27 status as a key factor is questionable.
To explore the prevalence and clinical associations of elevated systolic pulmonary artery pressure (sPAP), measured by Transthoracic Doppler-echocardiography (TTE) in patients with early systemic ...sclerosis (SSc).
A cross-sectional analysis of the prospective EULAR Scleroderma Trial and Research (EUSTAR) database was performed. SSc patients with <3 years from the first non-Raynaud's phenomenon (RP) symptom at baseline EUSTAR visit, were selected. Elevated sPAP was defined as sPAP>40 mmHg on baseline TTE. First visit SSc related variables, including disease subsets, antibodies and visceral involvement, were examined.
From 1,188 patients, 81% were women. Mean (SD) age at first non-RP symptom was 50 (14) years, 55% had limited cutaneous SSc (lcSSc) and 42% active disease. Elevated sPAP was found in 17% of patients, both lcSSc and diffuse cutaneous SSc (dcSSc). In lcSSc, older age at first non-RP symptom, ACA positivity, joint contractures, restrictive defect and lower DLCO, were independently associated with elevated sPAP. In dcSSc, older age at first non-RP symptom, longer time between RP onset and first non-RP symptom, digital ulcers, cardiac blocks, and proteinuria were associated with elevated sPAP.
The prevalence of elevated sPAP on TTE in early SSc patients is considerable. Association with cardiac, lung and renal involvement suggests that, although some patients might have pulmonary arterial hypertension, others may present pulmonary hypertension secondary to lung or heart involvement. Our findings emphasize the need to consider right heart catheterisation in selected early SSc patients with PH suspicion, to clearly determine the cause of PH.
ObjectiveSystemic sclerosis (SSc) is a systemic autoimmune disease with high morbidity and significant mortality. There is a great need of predictors that would allow risk stratification of patients ...with SSc and ultimately initiation of treatment early enough to ensure optimal clinical results. In this study, we evaluated whether a history of digital ulcers (HDU) at presentation may be a predictor of vascular outcomes and of overall clinical worsening and death in patients with SSc.MethodsPatients from the EULAR Scleroderma Trials and Research (EUSTAR) database, satisfying at inclusion the 1980 American College of Rheumatology classification criteria for SSc, who had a follow-up of at least 3 years since baseline or who have died, were included in the analysis. HDU at presentation as a predictor of disease worsening or death was evaluated by Cox proportional hazards regression analysis.Results3196 patients matched the inclusion criteria (male sex 13.2%, 33.4% diffuse subset). At presentation, 1092/3196 patients had an HDU (34.1%). In multivariable analysis adjusting for age, gender and all parameters considered potentially significant, HDU was predictive for the presence of active digital ulcers (DUs) at prospective visits (HR (95% CI)): 2.41 (1.91 to 3.03), p<0.001, for an elevated systolic pulmonary arterial pressure on heart ultrasound (US-PAPs):1.36 (1.03 to 1.80), p=0.032, for any cardiovascular event (new DUs, elevated US-PAPs or LV failure): 3.56 (2.26 to 5.62), p<0.001, and for death (1.53 (1.16 to 2.02), p=0.003).ConclusionsIn patients with SSc, HDU at presentation predicts the occurrence of DUs at follow-up and is associated with cardiovascular worsening and decreased survival.
Abstract
Objectives
Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed ...the effects of geographical locations.
Methods
SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.
Results
The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP. AP and BP were more likely to have pulmonary hypertension OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP and a reduced forced vital capacity OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004 than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001. After RP onset, AP and BP had a higher hazard to die than had WP hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001.
Conclusion
Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality.
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