The potential role of new oral anticoagulants in antiphospholipid antibody syndrome (APS) remains uncertain.
To determine whether rivaroxaban is noninferior to dose-adjusted vitamin K antagonists ...(VKAs) for thrombotic APS.
3-year, open-label, randomized noninferiority trial. (EU Clinical Trials Register: EUDRA European Union Drug Regulatory Authorities code 2010-019764-36).
6 university hospitals in Spain.
190 adults (aged 18 to 75 years) with thrombotic APS.
Rivaroxaban (20 mg/d or 15 mg/d, according to renal function) versus dose-adjusted VKAs (target international normalized ratio, 2.0 to 3.0, or 3.1 to 4.0 in patients with a history of recurrent thrombosis).
The primary efficacy outcome was the proportion of patients with new thrombotic events; the primary safety outcome was major bleeding. The prespecified noninferiority margin for risk ratio (RR) was 1.40. Secondary outcomes included time to thrombosis, type of thrombosis, changes in biomarker levels, cardiovascular death, and nonmajor bleeding.
After 3 years of follow-up, recurrent thrombosis occurred in 11 patients (11.6%) in the rivaroxaban group and 6 (6.3%) in the VKA group (RR in the rivaroxaban group, 1.83 95% CI, 0.71 to 4.76). Stroke occurred more commonly in patients receiving rivaroxaban (9 events) than in those receiving VKAs (0 events) (corrected RR, 19.00 CI, 1.12 to 321.9). Major bleeding occurred in 6 patients (6.3%) in the rivaroxaban group and 7 (7.4%) in the VKA group (RR, 0.86 CI, 0.30 to 2.46). Post hoc analysis suggested an increased risk for recurrent thrombosis in rivaroxaban-treated patients with previous arterial thrombosis, livedo racemosa, or APS-related cardiac valvular disease.
Anticoagulation intensity was not measured in the rivaroxaban group.
Rivaroxaban did not show noninferiority to dose-adjusted VKAs for thrombotic APS and, in fact, showed a non-statistically significant near doubling of the risk for recurrent thrombosis.
Bayer Hispania.
Objective
To compare the accuracy of the Birmingham Vasculitis Activity Score (BVAS), version 3, and the Five Factor Score (FFS), version 1996 and version 2009, to assess survival in antineutrophil ...cytoplasmic antibody–associated vasculitis (AAV).
Methods
A total of 550 patients with AAV (41.1% with granulomatosis with polyangiitis, 37.3% with microscopic polyangiitis, and 21.6% with eosinophilic granulomatosis with polyangiitis), diagnosed between 1990 and 2016, were analyzed. Receiver operating characteristic (ROC) curves and multivariable Cox analysis were used to assess the relationships between the outcome and the different scores.
Results
Overall mortality was 33.1%. The mean ± SD BVAS at diagnosis was 17.96 ± 7.82 and was significantly higher in nonsurvivors than in survivors (mean ± SD 20.0 ± 8.14 versus 16.95 ± 7.47, respectively; P < 0.001). The mean ± SD 1996 FFS and 2009 FFS were 0.81 ± 0.94 and 1.47 ± 1.16, respectively, and were significantly higher in nonsurvivors than in survivors (mean ± SD 1996 FFS 1.17 ± 1.07 versus 0.63 ± 0.81 P < 0.001 and 2009 FFS 2.13 ± 1.09 versus 1.15 ± 1.05 P < 0.001, respectively). Mortality rates increased according to the different 1996 FFS and 2009 FFS categories. In multivariate analysis, BVAS, 1996 FFS, and 2009 FFS were significantly related to death (P = 0.007, P = 0.020, P < 0.001, respectively), but the stronger predictor was the 2009 FFS (hazard ratio 2.9 95% confidence interval 2.4–3.6). When the accuracy of BVAS, 1996 FFS, and 2009 FFS to predict survival was compared in the global cohort, ROC analysis yielded area under the curve values of 0.60, 0.65, and 0.74, respectively, indicating that 2009 FFS had the best performance. Similar results were obtained when comparing these scores in patients diagnosed before and after 2001 and when assessing the 1‐year, 5‐year, and long‐term mortality. Correlation among BVAS and 1996 FFS was modest (r = 0.49; P < 0.001) but higher than between BVAS and the 2009 FFS (r = 0.28; P < 0.001).
Conclusion
BVAS and FFS are useful to predict survival in AAV, but the 2009 FFS has the best prognostic accuracy at any point of the disease course.
Objective To evaluate the clinical manifestations, long-term clinical outcome and longitudinal pulmonary function in a large cohort of Spanish patients with anti-Jo1 antibodies. Methods We ...retrospectively analysed the clinical data and lung function parameters of 148 anti-Jo1 patients recruited from a multicentre registry including 18 Spanish hospitals. A composite endpoint was defined, comprising death due to respiratory failure directly related to antisynthetase syndrome (ASS), the need for long-term oxygen therapy or lung transplantation. Results Median follow-up was 78.3 months. Clinical presentation patterns at onset: isolated interstitial lung disease (ILD) (32.4%), isolated myositis (26.9%), concomitant myositis and ILD (22.8%), and isolated polyarthritis (17.9%). Myositis with ILD was the most frequent final clinical phenotype (67.6%). In most ASS patients, ILD was a non-progressive disease, tending to stabilize with therapy. The endpoint was reached in a significantly larger number of ILD patients with dyspnoea at onset than those with paucisymptomatic or asymptomatic forms (p=0.01). A steady FVC decrease was the hallmark of patients with end-stage lung disease. Estimated survival rates were 87.7% and 75.4% at 5 and 10 years, respectively. Cancer (p=0.02) and advanced age at ASS diagnosis (p<0.0001) were related to poorer survival. Mortality was significantly higher than in the general Spanish population, with a standardised mortality ratio (95%CI) of 4.03 (2.79–5.64). Conclusions Anti-Jo1 ASS is a heterogeneous syndrome. ILD in ASS under immunosuppressive therapy is mainly a non-progressive disease. Dyspnoea at ILD onset and a steady FVC decrease over time were related to a poorer respiratory prognosis.
To analyse the clinical features, laboratory data and foetal-maternal outcomes, and follow them up on a cohort of 1000 women with obstetric antiphospholipid syndrome (OAPS).
The European Registry of ...OAPS became a registry within the framework of the European Forum on Antiphospholipid Antibody projects and was placed on a website in June 2010. Thirty hospitals throughout Europe have collaborated to carry out this registry. Cases with obstetric complaints related to antiphospholipid antibodies (aPL) who tested positive for aPL at least twice were included prospectively and retrospectively. The seven-year survey results are reported.
1000 women with 3553 episodes were included of which 2553 were historical and 1000 were latest episodes. All cases fulfilled the Sydney classification criteria. According to the laboratory categories, 292 (29.2%) were in category I, 357 (35.7%) in IIa, 224 (22.4%) in IIb and 127 (12.7%) in IIc. Miscarriages were the most prevalent clinical manifestation in 386 cases (38.6%). Moreover, the presence of early preeclampsia (PE) and early foetal growth restriction (FGR) appeared in 181 (18.1%) and 161 (16.1%), respectively. In this series, 448 (44.8%) women received the recommended OAPS treatment. Patients with recommended treatment had a good live-birth rate (85%), but worse results (72.4%) were obtained in patients with any treatment (low-dose aspirin (LDA) or low-molecular-weight heparin (LMWH) not on recommended schedule, while patients with no treatment showed a poor birth rate (49.6%).
In this series, recurrent miscarriage is the most frequent poor outcome. To avoid false-negative diagnoses, all laboratory category subsets were needed. OAPS cases have very good foetal-maternal outcomes when treated. Results suggest that we were able to improve our clinical practice to offer better treatment and outcomes to OAPS patients.
•OAPS is the most frequently treatable autoimmune disorder during pregnancy.•The classic antiphospholipid syndrome (APS) and the obstetric one (OAPS) have different rates of thromboses, response to treatment or follow-up.•According to our results, systemic and placental inflammation appears to play a major role in OAPS.•In our Registry all laboratory categories and clinical manifestation are represented.•The high rate of good foetal maternal outcomes and the fewer obstetric complications observed in the treated group requires clinicians to think about a standardised schedule for all OAPS patients.
Objectives
Several IgG4-related disease (IgG4-RD) phenotypes have been proposed and the first set of classification criteria have been recently created. Our objectives were to assess the phenotype ...distribution and the performance of the classification criteria in Spanish patients as genetic and geographical differences may exist.
Methods
We performed a cross-sectional multicentre study (Registro Español de Enfermedad Relacionada con la IgG4, REERIGG4) with nine participating centres from Spain. Patients were recruited from November 2013 to December 2018. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria (AECC) were used.
Results
We included 105 patients; 88% had Caucasian ethnicity. On diagnosis, 86% met the international pathology consensus while 92% met the Japanese comprehensive criteria. The phenotype distribution was head and neck 25%, Mikulicz and systemic (MS) 20%, pancreato-hepato-biliary (PHB) 13%, retroperitoneal and aorta (RA) 26%. Sixteen per cent had an undefined phenotype. Seventy-seven per cent of the cases met the AECC. From the 24 patients not meeting the AECC, 33% met exclusion criteria, and 67% did not get a score ≥20 points. Incomplete pathology reports were associated to failure to meet the AECC.
Conclusions
The PHB phenotype was rare among Spanish IgG4-RD patients. The MS phenotype was less frequent and the RA phenotype was more prevalent than in other, Asian patient series. An undefined phenotype should be considered as some patients do not fall into any of the categories. Three quarters of the cases met the 2019 AECC. Incomplete pathology reports were the leading causes of failure to meet the criteria.
Abstract
Objectives
To compare clinical features, laboratory data and fetal-maternal outcomes between 1000 women with obstetric APS (OAPS) and 640 with aPL-related obstetric complications not ...fulfilling Sydney criteria (non-criteria OAPS, NC-OAPS).
Methods
This was a retrospective and prospective multicentre study from the European Registry on Obstetric Antiphospholipid Syndrome.
Results
A total of 1650 women with 5251 episodes, 3601 of which were historical and 1650 latest episodes, were included. Altogether, 1000 cases (OAPS group) fulfilled the Sydney classification criteria and 650 (NC-OAPS group) did not. Ten NC-OAPS cases were excluded for presenting thrombosis during follow-up. All cases were classified as category I (triple positivity or double positivity for aPL) or category II (simple positivity). Overall, aPL laboratory categories showed significant differences: 29.20% in OAPS vs 17.96% in NC-OAPS (P < 0.0001) for category I, and 70.8% in OAPS vs 82% in NC-OAPS (P < 0.0001) for category II. Significant differences were observed when current obstetric complications were compared (P < 0.001). However, major differences between groups were not observed in treatment rates, livebirths and thrombotic complications. In the NC-OAPS group, 176/640 (27.5%) did not fulfil Sydney clinical criteria (subgroup A), 175/640 (27.34%) had a low titre and/or non-persistent aPL positivity but did meet the clinical criteria (subgroup B) and 289/640 (45.15%) had a high aPL titre but did not fulfil Sydney clinical criteria (subgroup C).
Conclusion
Significant clinical and laboratory differences were found between groups. Fetal-maternal outcomes were similar in both groups when treated. These results suggest that we could improve our clinical practice with better understanding of NC-OAPS patients.
To compare the efficacy and safety of enteric-coated mycophenolate sodium (EC-MPS) versus azathioprine (AZA) in patients with active systemic lupus erythematosus (SLE) disease.
A multicentre, ...24-month, superiority, open-label, randomised controlled trial (NCT01112215) was conducted with 240 patients (120 per arm) receiving either EC-MPS (target dose: 1440 mg/day) or AZA (target dose: 2 mg/kg/day) in addition to prednisone and/or antimalarials. The primary endpoint was the proportion of patients achieving clinical remission, assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and British Isles Lupus Assessment Group (BILAG), at 3 and 24 months. Secondary endpoints included time to clinical remission, BILAG A and B flare rates, time to flare, corticosteroid reduction and adverse events (AEs).
Proportion of patients achieving clinical remission (clinical SLEDAI=0) was higher in the EC-MPS group at 3 (32.5% vs 19.2%; treatment difference, 13.3 (CI 2.3 to 24), p=0.034) and 24 months (71.2% vs 48.3%; treatment difference, 22.9 (CI 10.4 to 34.4), p<0.001). EC-MPS was superior with respect to time to clinical remission (HR 1.43; 95% CI 1.07 to 1.91; p=0.017). BILAG A/B and B flares occurred more frequently in the AZA group (71.7% vs 50%, p=0.001 and 21.67% vs 8.3%, p=0.004, respectively). EC-MPS was superior with respect to time to first BILAG A/B (HR 1.81; 95% CI 1.3 to 2.56; p=0.0004) and BILAG A flare (HR 2.84; 95% CI 1.37 to 5.89; p=0.003). AEs were similar in both groups except for leucopenia that occurred more frequently with AZA.
EC-MPS was superior to AZA in treating SLE and preventing further relapses.
NCT01112215; Results.
The European Alliance of Associations for Rheumatology (EULAR) supports the use of nailfold videocapillaroscopy (NVC) to identify disease patterns (DPs) associated with systemic sclerosis (SSc) and ...Raynaud's phenomenon (RP). Recently, EULAR proposed an easy-to-manage procedure, a so-called Fast Track algorithm, to differentiate SSc from non-SSc patterns in NVC specimens. However, subjectivity among capillaroscopists remains a limitation. Our aim was to perform a software-based analysis of NVC peculiarities in a cohort of samples from SSc and RP patients and, subsequently, build a Fast Track-inspired algorithm to identify DPs without the constraint of interobserver variability.
NVCs were examined by 9 capillaroscopists. Those NVCs whose DPs were consensually agreed (≥2 out of 3 interobservers) were subsequently analysed with an in-house developed software. Each variable's results were grouped according to the consensually agreed DPs in order to identify useful hallmarks to categorise them.
Eight-hundred and fifty-one NVCs (21 957 images) whose DPs had been consensually agreed were software-analysed. Appropriate cut-offs set in capillary density and percentage of abnormal and giant capillaries, tortuosities and hemorrhages allowed DP categorization and the development of the CAPI-Score algorithm. This consisted of 4 rules: Rule 1, SSc vs non-SSc, accuracy 0.88; Rules 2 and 3, SSc-early vs SSc-active vs SSc-late, accuracy 0.82; Rule 4, non-SSc normal vs non-SSc non-specific, accuracy 0.73. Accuracy improved when the analysis was limited to NVCs whose DPs had achieved full consensus among interobservers.
The CAPI-Score algorithm may become a useful tool to assign DPs by overcoming the limitations of subjectivity.
To map existing organizational care pathways in clinical centers of expertise that care for pregnant women affected by rare and complex connective tissue diseases (rcCTDs).
An international working ...group composed of experts in the field of pregnancy in rcCTDs co-designed a survey focused on organizational aspects related to the patient's pathway before, during, and after pregnancy. The survey was distributed to subject experts through referral sampling.
Answers were collected from 69 centers in 21 countries. Patients with systemic lupus erythematosus and/or antiphospholipid syndrome were followed by more than 90% of centers, whereas those with disorders such as IgG4-related diseases were rarely covered. In the majority of centers, a multidisciplinary team was involved, including an obstetrician/gynecologist in 91.3% of cases and other healthcare professionals less frequently. Respondents indicated that 96% of the centers provided routine pre-pregnancy care, whereas the number of patient visits during pregnancy varied across centers. A formalized care pathway was described in 49.2% of centers, and 20.3% of centers had a predefined protocol for the monitoring of pregnant patients. Access to therapies during pregnancy also was heterogeneous among different centers.
In international referral centers, a high level of care is provided to patients with rcCTDs before, during, and after pregnancy. No significant discrepancies were found between European and non-European countries. However, this work highlights a potential benefit to streamlining the care approaches across countries to optimize pregnancy and perinatal outcomes among patients with rcCTDs.
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