A projected cost-utility analysis of avacopan for the treatment of antineutrophil cytoplasmic antibody-associated vasculitis in Spain.

BACKGROUND: Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are rare autoimmune diseases characterized by inflammation of blood vessels. This study aimed to assess the cost-utility of avacopan in combination with rituximab (RTX) or cyclophosphamide (CYC) compared with glucocorticoids (GC) for the treatment of severe, active AAV in Spain. METHODS: A 9-state Markov model was designed to reflect the induction of remission and sustained remission of AAV over a lifetime horizon. Clinical data and utility values were mainly obtained from the ADVOCATE trial, and costs (€ 2022) were sourced from national databases. Quality-adjusted life years (QALYs), and incremental cost-utility ratio (ICUR) were evaluated. An annual discount rate of 3% was applied. Sensitivity analyses were performed to examine the robustness of the results. RESULTS: Avacopan yielded an increase in effectiveness (6.52 vs. 6.17 QALYs) and costs (€16,009) compared to GC, resulting in an ICUR of €45,638 per additional QALY gained. Avacopan was associated with a lower incidence of end-stage renal disease (ESRD), relapse and hospitalization-related adverse events. Sensitivity analyses suggested that the model outputs were robust and that the progression to ESRD was a driver of ICUR. CONCLUSIONS: Avacopan is a cost-effective option for patients with severe, active AAV compared to GC in Spain.

Expert consensus on the use of systemic glucocorticoids for managing eosinophil-related diseases.

Eosinophil-related diseases represent a group of pathologic conditions with highly heterogeneous clinical presentation and symptoms ranging from mild to critical. Both systemic and localized forms of disease are typically treated with glucocorticoids. The approval of novel biologic therapies targeting the interleukin-5 pathway can help reduce the use of systemic glucocorticoids (SGC) in eosinophilic diseases and reduce the risk of SGC-related adverse effects (AEs). In this article, a panel of experts from different medical specialties reviewed current evidence on the use of SGC in two systemic eosinophilic diseases: Eosinophilic Granulomatosis with PolyAngiitis (EGPA) and HyperEosinophilic Syndrome (HES); and in two single-organ (respiratory) eosinophilic diseases: Chronic RhinoSinusitis with Nasal Polyps (CRSwNP) and Severe Asthma with Eosinophil Phenotype (SA-EP), and contrasted it with their experience in clinical practice. Using nominal group technique, they reached consensus on key aspects related to the dose and tapering of SGC as well as on the initiation of biologics as SGC-sparing agents. Early treatment with biologics could help prevent AEs associated with medium and long-term use of SGC.

Characterization and outcomes of 414 patients with primary SS who developed haematological malignancies.

OBJECTIVE: To characterize 414 patients with primary SS who developed haematological malignancies and to analyse how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes. METHODS: By January 2021, the Big Data Sjögren Project Consortium database included 11 966 patients fulfilling the 2002/2016 classification criteria. Haematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified. RESULTS: There were 414 patients (355 women, mean age 57 years) with haematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). A total of 376 (91%) patients had mature B-cell malignancy, nearly half had extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT lymphoma) (n = 197), followed by diffuse large B-cell lymphoma (DLBCL) (n = 67), nodal MZL lymphoma (n = 29), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n = 19) and follicular lymphoma (FL) (n = 17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8 years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL). CONCLUSION: In the largest reported study of haematological malignancies complicating primary SS, we confirm the overwhelming predominance of B-cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%.

Are Temporal Artery Biopsy Findings Related to PET/CT Findings in Giant Cell Arteritis?

BACKGROUND: Two clinical subsets of giant cell arteritis have been identified with different histological and CT findings. However, PET/CT findings have not been compared with temporal artery biopsy (TAB). OBJECTIVE: The aims of this study were to describe clinical and histological findings in patients with giant cell arteritis according to the presence or absence of aortitis in PET/CT at the disease diagnosis, and to identify independent factors related to aortic involvement. METHODS: Patients were included and followed prospectively. Clinical symptoms and TAB findings were recorded. PET/CT was performed in the first 10 days of steroid therapy. Aortitis was defined if a grade 3 uptake on visual analysis was present on arterial wall. Clinical and histological variables were compared according to the presence or absence of aortitis on PET/CT. Multivariate analysis was performed to identify independent factors related to the presence of aortitis. RESULTS: Twenty-seven patients (median age, 77.6 years) were included. PET/CT was performed with a median delay of 5.0 days. Aortitis was observed in 8 patients. Patients with aortitis were younger (69.9 vs 83.7 years, P = 0.04) and had less frequently ischemic manifestations (25.0% vs 84.2%, P = 0.006) than patients without aortitis. Giant multinucleated cells were more frequent on TAB from patients with aortitis (71.4% vs 16.7%), and its presence was an independent risk factor for the occurrence of aortic involvement on PET/CT (odds ratio, 12.2; P = 0.046). CONCLUSIONS: Our study shows that giant cells on TAB are associated with the presence of aortitis on PET/CT. Patients with aortic involvement are younger and show less frequently ischemic manifestations.

Recurrent thrombosis as a clinical presentation of Whipple disease.

Whipple's disease (WD) is a rare infectious disease with a wide clinical spectrum. Associated thrombotic manifestations are not well described in WD, only related to 'stroke-like syndrome'. We present a case of a 39-year-old man with a 1-year history of self-limited episodes of fever, associated with generalised adenopathies and recurrent superficial and deep venous thrombosis events, which have resorted four times despite the anticoagulant treatment. Finally, the patient is diagnosed with WD. Following treatment the patient improved in his general condition, and no more episodes of fever neither thrombosis appeared during a follow-up of more than 3 years.

Síndrome de Sjögren y afectación pulmonar / Pulmonary involvement in Sjögren's syndrome

El síndrome de Sjögren es una enfermedad autoinmune que afecta a las glándulas exocrinas. Su sintomatología característica es el síndrome seco en forma de xeroftalmia y xerostomía, pero puede afectar a diversos órganos o sistemas y la afectación extraglandular es la que condiciona el pronóstico de la enfermedad. Típicamente se asocia con la presencia de anticuerpos antinucleares, que incluyen anti-Ro-60. La afectación pulmonar aparece en forma de bronquiectasias y/o neumopatía intersticial. Dada la alta prevalencia de esta complicación, su presencia debe descartarse en todos los pacientes con síntomas respiratorios mediante pruebas de función respiratoria y tomografía computarizada de alta resolución torácica. Se puede completar la valoración mediante biopsia transbronquial en aquellos casos en que existan dudas diagnósticas. El tratamiento incluye glucocorticoterapia, terapia inmunosupresora o antifibrótica, y terapia biológica. En caso de mala evolución se debe valorar el trasplante pulmonar.

Sjögren's syndrome is an autoimmune disease that involves exocrine glands. The most characteristic symptoms consist of the sicca syndrome (including xerostomia and dry eye – xerophtalmia), but can involve multiple organs. The extraglandular involvement determines the prognosis. It is typically associated with the presence of antinuclear antibodies, including Ro-60 antibodies. Pulmonary involvement appears as bronchiectasis and/or interstitial pneumonia. Considering its high prevalence, it must be ruled out in all patients with respiratory symptoms by performing pulmonary function tests and high-resolution computed tomography of the chest. Evaluation can be completed with a transbronchial biopsy if diagnostic doubts persist. Treatment includes steroid therapy, inmunosupressive or antifibrotic drugs, or biological therapy. In selected cases pulmonary transplantation must be considered. (AU)

[Pulmonary involvement in Sjögren's syndrome]. / Síndrome de Sjögren y afectación pulmonar.

Sjögren's syndrome is an autoimmune disease that involves exocrine glands. The most characteristic symptoms consist of the sicca syndrome (including xerostomia and dry eye - xerophtalmia), but can involve multiple organs. The extraglandular involvement determines the prognosis. It is typically associated with the presence of antinuclear antibodies, including Ro-60 antibodies. Pulmonary involvement appears as bronchiectasis and/or interstitial pneumonia. Considering its high prevalence, it must be ruled out in all patients with respiratory symptoms by performing pulmonary function tests and high-resolution computed tomography of the chest. Evaluation can be completed with a transbronchial biopsy if diagnostic doubts persist. Treatment includes steroid therapy, inmunosupressive or antifibrotic drugs, or biological therapy. In selected cases pulmonary transplantation must be considered.

Serum CXCL13, BAFF, IL-21 and IL-22 levels are related to disease activity and lymphocyte profile in primary Sjögren's syndrome.

OBJECTIVES: To investigate the utility of serum BAFF, IL-17, IL-18, IL-21, IL-22, CXCL13, TNF-R2 and PD-L2 as biomarkers of disease activity in primary Sjögren's syndrome (pSS), their relationship with lymphocyte subpopulations and their accuracy to discriminate pSS from Sicca syndrome. METHODS: We conducted an observational study on 66 pSS patients and 48 controls (25 with Sicca syndrome and 23 healthy volunteers). Serum levels of BAFF, IL-17 A/F, IL-18, IL-21, IL-22, CXCL13, TNF-R2 and PD-L2 were measured using a multiplex immunoassay. Lymphocyte subpopulations were analysed by flow cytometry. Disease activity of pSS was assessed with ESSDAI at study inclusion. RESULTS: Patients with pSS presented higher serum CXCL13 (364.7 vs. 205.2 pg/mL), IL-21 (43.2 vs. 0 pg/mL) and BAFF (1646 vs. 1369 pg/mL), and lower PD-L2 levels (1950.8 vs. 2792.3 pg/mL) than controls. ESSDAI was associated with BAFF, IL-18 and IL-22. Patients with ESSDAI >0 exhibited higher CXCL13, IL-21, IL-22 and TNFR2 concentrations. IL-21 levels correlated with lower memory B-cell and higher naïve B-cell percentages and IL-22 levels correlated with increased circulating activated CD4+ T-cells. The combination of serum CXCL13, BAFF and PDL2 levels using the formula [ln(CXCL13)+ln(BAFF)]/ln(PDL2) exhibit an AUC of 0.854 (95% CI: 0.750-0.919) to discriminate between pSS and Sicca syndrome (sensitivity 77.2% and specificity 86.4% using a cut-off of 1.7). CONCLUSIONS: CXCL13, BAFF, IL-21, and IL-22 are potential biomarkers of pSS activity and IL-21 and IL-22 are associated with disturbances of lymphocyte subpopulations in pSS. The combination of serum CXCL13, BAFF, and PD-L2 levels allows discrimination between pSS and Sicca syndrome.

Influence of the age at diagnosis in the disease expression of primary Sjögren syndrome. Analysis of 12,753 patients from the Sjögren Big Data Consortium.

OBJECTIVES: To analyse how the main components of the disease phenotype (sicca symptoms, diagnostic tests, immunological markers and systemic disease) can be driven by the age at diagnosis of primary Sjögren's syndrome (pSS). METHODS: By January 2021, the participant centres had included 12,753 patients from 25 countries that fulfilled the 2002/2016 classification criteria for pSS. The age at diagnosis was defined as the time when the attending physician confirmed fulfilment of the criteria. Patients were clustered according to age at diagnosis. 50 clusters with more than 100 observations (from 27 to 76 years) were used to study the influence of the age at diagnosis in the disease expression. RESULTS: There was a consistent increase in the frequency of oral dryness according to the age at diagnosis, with a frequency of <90% in patients diagnosed at the youngest ages and >95% in those diagnosed at the oldest ages. The smooth curves that best fitted a linear model were the frequency of dry mouth (adjusted R2 0.87) and the frequency of abnormal oral tests (adjusted R2 0.72). Therefore, for each 1-year increase in the age at diagnosis, the frequency of dry mouth increased by 0.13%, and the frequency of abnormal oral diagnostic tests by 0.11%. There was a consistent year-by-year decrease in the frequency of all autoantibodies and immunological markers except for cryoglobulins. According to the linear models, for each 1-year increase in the age at diagnosis, the frequency of a positive result decreased by 0.57% (for anti-Ro antibodies), 0.47% (for RF) and 0.42% (for anti-La antibodies). The ESSDAI domains which showed a more consistent decrease were glandular and lymph node involvement (for each 1-year increase in the age at diagnosis, the frequency of activity decreased by 0.18%), and constitutional, cutaneous, and haematological involvements (the frequency decreased by 0.09% for each 1-year increase). In contrast, other domains showed an ascending pattern, especially pulmonary involvement (for each 1-year increase in the age at diagnosis, the frequency of activity increased by 0.22%), and peripheral nerve involvement (the frequency increased by 0.09% for each 1-year increase). CONCLUSIONS: The influence of the age at diagnosis on the key phenotypic features of pSS is strong, and should be considered critical not only for designing a personalised diagnostic approach, but also to be carefully considered when analysing the results of diagnostic tests and immunological parameters, and when internal organ involvement is suspected at diagnosis.

Tocilizumab in refractory Caucasian Takayasu's arteritis: a multicenter study of 54 patients and literature review.

OBJECTIVE: To assess the efficacy and safety of tocilizumab (TCZ) in Caucasian patients with refractory Takayasu's arteritis (TAK) in clinical practice. METHODS: A multicenter study of Caucasian patients with refractory TAK who received TCZ. The outcome variables were remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A comparative study between patients who received TCZ as monotherapy (TCZMONO) and combined with conventional disease modifying anti-rheumatic drugs (cDMARDs) (TCZCOMBO) was performed. RESULTS: The study comprised 54 patients (46 women/8 men) with a median [interquartile range (IQR)] age of 42.0 (32.5-50.5) years. TCZ was started after a median (IQR) of 12.0 (3.0-31.5) months since TAK diagnosis. Remission was achieved in 12/54 (22.2%), 19/49 (38.8%), 23/44 (52.3%), and 27/36 (75%) patients at 1, 3, 6, and 12 months, respectively. The prednisone dose was reduced from 30.0 mg/day (12.5-50.0) to 5.0 (0.0-5.6) mg/day at 12 months. An improvement in imaging findings was reported in 28 (73.7%) patients after a median (IQR) of 9.0 (6.0-14.0) months. Twenty-three (42.6%) patients were on TCZMONO and 31 (57.4%) on TCZCOMBO: MTX (n = 28), cyclosporine A (n = 2), azathioprine (n = 1). Patients on TCZCOMBO were younger [38.0 (27.0-46.0) versus 45.0 (38.0-57.0)] years; difference (diff) [95% confidence interval (CI) = -7.0 (-17.9, -0.56] with a trend to longer TAK duration [21.0 (6.0-38.0) versus 6.0 (1.0-23.0)] months; diff 95% CI = 15 (-8.9, 35.5), and higher c-reactive protein [2.4 (0.7-5.6) versus 1.3 (0.3-3.3)] mg/dl; diff 95% CI = 1.1 (-0.26, 2.99). Despite these differences, similar outcomes were observed in both groups (log rank p = 0.862). Relevant adverse events were reported in six (11.1%) patients, but only three developed severe events that required TCZ withdrawal. CONCLUSION: TCZ in monotherapy, or combined with cDMARDs, is effective and safe in patients with refractory TAK of Caucasian origin.

Utility of lymphocyte phenotype profile to differentiate primary Sjögren's syndrome from sicca syndrome.

OBJECTIVE: To assess the potential diagnostic utility of advanced lymphocyte profiling to differentiate between primary Sjögren's Syndrome (pSS) and non-Sjögren Sicca syndrome. METHODS: Distribution of peripheral lymphocyte subpopulations was analysed by flow cytometry in 68 patients with pSS, 26 patients with sicca syndrome and 23 healthy controls. The ability to discriminate between pSS and sicca syndrome was analysed using the area under the curve (AUC) of the receiver operating characteristic curve of the different lymphocyte subsets. RESULTS: The ratio between naïve/memory B cell proportions showed an AUC of 0.742 to differentiate pSS and sicca syndrome, with a sensitivity of 76.6% and a specificity of 72% for a cut-off value of 3.4. The ratio of non-switched memory B cells to activated CD4+ T cells percentage (BNSM/CD4ACT) presented the highest AUC (0.840) with a sensitivity of 83.3% and specificity of 81.7% for a cut-off value <4.1. To differentiate seronegative pSS patients from sicca patients, the BNSM/CD4ACT ratio exhibited an AUC of 0.742 (sensitivity 75%, specificity 66.7%, cut-off value <4.4), and the number of naïve CD4 T cells had an AUC of 0.821 (sensitivity 76.9%, specificity 88.9%, cut-off value <312/mm3). CONCLUSION: Patients with pSS show a profound imbalance in the distribution of circulating T and B lymphocyte subsets. The ratio BNSM/CD4ACT is useful to discriminate between pSS and sicca syndrome.

Heart disease in eosinophilic granulomatosis with polyangiitis (EGPA) patients: a screening approach proposal.

OBJECTIVE: To define the pattern of cardiac involvement in eosinophilic granulomatosis and polyangiitis (EGPA) and propose an algorithm for heart disease screening. METHODS: This was a retrospective study of EGPA patients attending a specialized vasculitis clinic (1989-2016). Clinical characteristics and cardiovascular evaluation (CE) results (serum troponin, ECG, echocardiography and cardiac magnetic resonance) were collected and compared according to symptoms and inflammatory cardiac disease (ICD). RESULTS: A total of 131 EGPA patients were included, of whom 96 (73%) had undergone CE. The median (interquartile range) age was 50 (38-58) years and 36% showed ANCA+. Asthma preceded diagnosis by a median of 97 (36-240) months. Among the 96 patients who underwent CE, 43% were symptomatic, with dyspnea (47%) and chest pain (29%) being the predominant symptoms. In asymptomatic patients, CE reported abnormalities in 45% of cases, with a subsequent earlier diagnosis (4 vs 11 months). Overall, 27 patients had EGPA-related ICD (EGPA-rICD) that was already present at diagnosis in 20 cases, preceded it in 2 cases and developed later in 5 cases. EGPA-rICD patients were younger (46 vs 50 years; P = 0.04), had more frequently abnormal ECG (30.8 vs 2.1%; P < 0.001), negative ANCA (85 vs 69%; NS), higher BVAS score (3 vs 1; P = 0.005), higher eosinophil count (5.60 vs 1.60 × 109/l; P = 0.029) and higher CRP (52 vs 15 mg/l; P = 0.017). Overall, 11% of cases with EGPA-rICD were asymptomatic. CONCLUSION: In our study, 45% of asymptomatic patients had an abnormal baseline cardiac evaluation, which allowed an earlier diagnosis of cardiac disease. We recommend prompt cardiac screening in all EGPA patients, instead of a symptoms-guided algorithm.

Tocilizumab in giant cell arteritis: differences between the GiACTA trial and a multicentre series of patients from the clinical practice.

OBJECTIVES: A potential point of concern among clinicians is whether results derived from the clinical trials can be reasonably applied or generalised to a definable group of patients seen in real world. It can be the case of the GiACTA study that is a phase III randomised controlled trial of tocilizumab (TCZ) in giant cell arteritis (GCA). To address this question, we compared the clinical features and the responses to TCZ from the GiACTA trial patients with those from a series of GCA seen in the daily clinical practice. METHODS: Comparative study of clinical features between patients from the GiACTA trial (overall n=251) and those from a multicentre series of real-world GCA patients undergoing TCZ therapy (n=134). The diagnosis of GCA in the GiACTA trial was established by the ACR modified criteria whereas in the series of real-world patients it was made by using the ACR criteria, a positive biopsy of temporal artery or the presence of imaging techniques consistent with large-vessel vasculitis in individuals who presented cranial symptoms of GCA. GiACTA trial patients received subcutaneous TCZ (162 mg every 1 or 2 weeks) whereas those from the clinical practice series were treated using standard IV dose (8 mg/kg/month) or subcutaneous (162 mg/week). RESULTS: Real-life patients undergoing TCZ were older with longer disease duration and higher values of ESR and had received conventional immunosuppressive therapy (mainly methotrexate) more commonly than those included in the GiACTA trial. Despite clinical differences, TCZ was equally effective in both GiACTA trial and clinical practice patients. However, serious infections were more commonly observed in GCA patients recruited from the clinical practice. CONCLUSIONS: Despite clinical differences with patients recruited in clinical trials, data from real-life patients confirm the efficacy of TCZ in GCA.

Prevalence and Risk Factors for Major Infections in Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitis: Influence on the Disease Outcome.

OBJECTIVE: To analyze the role that infections play on the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) outcome. METHODS: A retrospective study of adult patients with AAV diagnosed in a tertiary center. Clinical features, laboratory findings, treatment, relapses, major infections, and outcome were evaluated. RESULTS: Included were 132 patients [51 microscopic polyangiitis (MPA), 52 granulomatosis with polyangiitis (GPA), 29 eosinophilic GPA (EGPA)] with a mean followup of 140 (96-228) months. ANCA were positive in 85% of cases. A total of 300 major infections, mainly bacterial (85%), occurred in 60% patients during the followup. Lower respiratory tract (64%) and urinary tract infections (11%) were the most frequent, followed by bacteremia (10%). A total of 7.3% opportunistic infections were observed, most due to systemic mycosis. Up to 46% of all opportunistic infections took place in the first year of diagnosis, and 55% of them under cyclophosphamide (CYC) treatment. Bacterial infections were associated with Birmingham Vasculitis Activity Score (version 3) > 15 at the disease onset, a total cumulative CYC dose > 8.65 g, dialysis, and development of leukopenia during the followup. Leukopenia was the only factor independently related to opportunistic infections. Forty-four patients died, half from infection. Patients who had major infections had an increased mortality from any cause. CONCLUSION: Our results confirm that major infections are the main cause of death in patients with AAV.

Comparison of the Birmingham Vasculitis Activity Score and the Five-Factor Score to Assess Survival in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Study of 550 Patients From Spain (REVAS Registry).

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.

Risk of ischaemic events at giant cell arteritis diagnosis according to PET/CT findings.

PURPOSE: To analyse the risk of ischaemic events in patients with newly diagnosed giant cell arteritis (GCA) according to PET/CT findings. METHODS: PET/CT was performed during the first 10 days of steroid therapy. Clinical manifestations at diagnosis, and physical examination and PET/CT findings were recorded and compared according to the presence or absence of ischaemic symptoms at disease onset. Analysed territories included the ascending aorta, aortic arch, descending aorta, abdominal aorta, carotid arteries, brachiocephalic trunk, vertebral arteries, subclavian arteries and axillary arteries. RESULTS: The study group comprised 30 patients with a median age of 80.8 years. Of these patients, 21 (70%) reported ischaemic symptoms at diagnosis, and 13 (43.3%) had permanent visual loss. Of the 30 patients, 77.8% showed large vessel vasculitis (including aortic and vertebral artery involvement) on PET/CT, and 60% had isolated involvement of the vertebral territory. Vertebral arteries were more frequently involved in patients with ischaemic symptoms (OR 5.0, 95% CI 0.99-24.86, p = 0.051). The presence of vertebral artery involvement in the absence of aortic involvement was associated with the presence of ischaemic manifestations (Fisher's exact test, p = 0.001). The presence of aortitis was found to protect against the development of permanent visual loss (OR 19.0, 95% CI 2.79-127.97, p = 0.001). CONCLUSION: Our findings suggest an association between the vascular pattern on PET/CT at the time of GCA diagnosis and the risk of ischaemic events.

Tocilizumab in giant cell arteritis. Observational, open-label multicenter study of 134 patients in clinical practice.

OBJECTIVE: Tocilizumab (TCZ) has shown efficacy in clinical trials on giant cell arteritis (GCA). Real-world data are scarce. Our objective was to assess efficacy and safety of TCZ in unselected patients with GCA in clinical practice Methods: Observational, open-label multicenter study from 40 national referral centers of GCA patients treated with TCZ due to inefficacy or adverse events of previous therapy. Outcomes variables were improvement of clinical features, acute phase reactants, glucocorticoid-sparing effect, prolonged remission and relapses. A comparative study was performed: (a) TCZ route (SC vs. IV); (b) GCA duration (≤6 vs. >6 months); (c) serious infections (with or without); (d) ≤15 vs. >15 mg/day at TCZ onset. RESULTS: 134 patients; mean age, 73.0 ± 8.8 years. TCZ was started after a median [IQR] time from GCA diagnosis of 13.5 [5.0-33.5] months. Ninety-eight (73.1%) patients had received immunosuppressive agents. After 1 month of TCZ 93.9% experienced clinical improvement. Reduction of CRP from 1.7 [0.4-3.2] to 0.11 [0.05-0.5] mg/dL (p < 0.0001), ESR from 33 [14.5-61] to 6 [2-12] mm/1st hour (p < 0.0001) and decrease in patients with anemia from 16.4% to 3.8% (p < 0.0001) were observed. Regardless of administration route or disease duration, clinical improvement leading to remission at 6, 12, 18, 24 months was observed in 55.5%, 70.4%, 69.2% and 90% of patients. Most relevant adverse side-effect was serious infections (10.6/100 patients-year), associated with higher doses of prednisone during the first three months of therapy. CONCLUSION: In clinical practice, TCZ yields a rapid and maintained improvement of refractory GCA. Serious infections appear to be higher than in clinical trials.

Utility of the 18F-Florbetapir positron emission tomography in systemic amyloidosis.

Amyloidosis comprises a group of heterogeneous conditions. To ascertain the burden of disease is important because it can determine the treatment as well as the evolution of the disease. Recent reports have shown good results in diagnosing cardiac amyloidosis using 18F-florbetapir. We hypothesize that combining whole body PET/CT with 18F-Florbetapir can be useful to characterize the burden of the disease. We included 25 patients, 13 of them with different types of amyloidosis, and 12 with Alzheimer's disease as controls. Target-to-background ratio was computed for multiple organ using maximum standardized uptake values. Organ involvement was described (standardized techniques versus PET) according to different kinds of amyloidosis showing promising results in AA and AL types. Heart involvement showed poorer results when compared to tongue, lung or thyroid gland. Multiple organ involvement in patients previously labelled as having negative organ affectation could be identified. This is the first study to evaluate the utility of 18F-florbetapir in the assessment of the global extension of disease. Our results show that this technique is useful for its diagnosis.

Clinical characteristics and outcome of Spanish patients with ANCA-associated vasculitides: Impact of the vasculitis type, ANCA specificity, and treatment on mortality and morbidity.

The aim of this study was to describe the clinical characteristics of ANCA-associated vasculitides (AAV) at presentation, in a wide cohort of Spanish patients, and to analyze the impact of the vasculitis type, ANCA specificity, prognostic factors, and treatments administered at diagnosis, in the outcome.A total of 450 patients diagnosed between January 1990 and January 2014 in 20 Hospitals from Spain were included. Altogether, 40.9% had granulomatosis with polyangiitis (GPA), 37.1% microscopic polyangiitis (MPA), and 22% eosinophilic granulomatosis with polyangiitis (EGPA). The mean age at diagnosis was 55.6 ±â€Š17.3 years, patients with MPA being significantly older (P < 0.001). Fever, arthralgia, weight loss, respiratory, and ear-nose-throat (ENT) symptoms, were the most common at disease onset. ANCAs tested positive in 86.4% of cases: 36.2% C-ANCA-PR3 and 50.2% P-ANCA-MPO. P-ANCA-MPO was significantly associated with an increased risk for renal disease (OR 2.6, P < 0.001) and alveolar hemorrhage (OR 2, P = 0.010), while C-ANCA-PR3 was significantly associated with an increased risk for ENT (OR 3.4, P < 0.001) and ocular involvement (OR 2.3, P = 0.002). All patients received corticosteroids (CS) and 74.9% cyclophosphamide (CYC). The median follow-up was 82 months (IQR 100.4). Over this period 39.9% of patients suffered bacterial infections and 14.6% opportunistic infections, both being most prevalent in patients with high-cumulated doses of CYC and CS (P < 0.001). Relapses were recorded in 36.4% of cases with a mean rate of 2.5 ±â€Š2.3, and were more frequent in patients with C-ANCA-PR3 (P = 0.012). The initial disease severity was significantly associated with mortality but not with the occurrence of relapses. One hundred twenty-nine (28.7%) patients (74 MPA, 41 GPA, 14 EGPA) died. The mean survival was 58 months (IQR 105) and was significantly lower for patients with MPA (P < 0.001). Factors independently related to death were renal involvement (P = 0.010), cardiac failure (P = 0.029) and age over 65 years old (P < 0.001) at disease onset, and bacterial infections (P < 0.001). An improved outcome with significant decrease in mortality and treatment-related morbidity was observed in patients diagnosed after 2000, and was related to the implementation of less toxic regimens adapted to the disease activity and stage, and a drastic reduction in the cumulated CYC and CS dose.