FRI0191 CRANIAL-LIMITED AND LARGE-VESSEL GIANT CELL ARTERITIS: PRESENTING FEATURES AND OUTCOME

Background:Giant cell arteritis (GCA) comprises two main phenotypes: cranial (C) and large-vessel (LV) disease1. A full baseline steroid-free vascular imaging evaluation is required to properly diagnose LV involvement2Objectives:To compare presenting and prognostic features of LV-GCA and C-GCA patients after an adequate vascular imaging evaluation at baselineMethods:Data from GCA patients followed-up at our Institution were retrospectively collected. Only patients who underwent large-vessel imaging (PET, CTA, MRA) at disease onset or within 1 week after steroid introduction were included. Patients with evidence of LV involvement were classified as LV-GCA. Differences between LV-GCA and C-GCA patients regarding presenting features, treatment, prognosis were evaluated. Non-parametric tests were usedResults:In our cohort, we identified 161/280 patients who underwent LV-imaging study at baseline. Of these, 100 (62.1%) had signs of LV inflammation. Table 1 compares demographic features, diagnostic delay, pre-existing comorbidities and complementary treatment between the 2 groups. Table 2 compares disease features at diagnosis. Mean follow-up was similar between LV- and C-GCA patients (31.8±31.8 vs 27.8±29.1 months; 70% vs 73.8% followed-up ≥12 months). Corrected cumulative prednisone dose (CCPD, grams/months) was equivalent (LV, 0.67±0.57; C, 0.87±1.37; p=0.871). A DMARD was added in 73% of LV- and in 55.7% of C-GCA patients (p=0.027), but, notably, it was introduced at baseline in 52% of LV- vs 23.5% of C-GCA patients (p=0.006). CCPD was equivalent even considering only patients who did not receive DMARDs (LV, 0.92±0.81; C, 0.94±1.18; p=0.522). Frequency of relapses was not significantly different (LV, 51%; C, 57.3%, p=0.515), even when considering only DMARD-receiving patients (LV, 36.1%; C, 38.2%, p=0.833). Aortic aneurysms incidence at 5 years was similar (LV, 17.3%; C, 15.7%; p=0.826). Rate of metabolic and infective complications was similar, in terms of arterial hypertension (LV, 3%; C, 0%, p=0.286), diabetes (2% vs 0%, p=0.524), osteoporotic fractures (7% vs 5%, p=0.742), severe infections (3% vs 3.3%, p=1)Table 1.Demographic features, diagnostic delay, pre-existing comorbidities, and complementary treatment at baseline in LV and C-GCA patientsLV imaging +n=100 (%)LV imaging-n=61 (%)p-valueAge (years)73.2 ± 8.976 ± 8.80.018Sex (female)65 (65)40 (65)1Diagnostic delay (months)3.5 ± 4.62.3 ± 4.90.001Pre-existing comorbidities- CAD3 (3)7 (11.5)0.043- Diabetes4 (4)6 (9.8)0.181- Dyslipidemia17 (17)17 (27.9)0.114- Hypertension42 (42)34 (55.7)0.105- Stroke3 (3)3 (5)0.674- Cancer20 (20)6 (9.8)0.122Ongoing complementary treatment- Antiplatelet18 (18)15 (25)0.322- Anticoagulant1 (1)6 (9.8)0.012- Statin14 (14)14 (23)0.198Table 2.Diseases features at onset in LV and C-GCA patientsLV imaging +n=100 (%)LV imaging-n=61 (%)p-valueTemporal biopsy positive17/31 (55)9(43)0.573Symptoms- Headache65 (65)52 (85)0.006- Jaw claudication22 (22)20 (32.8)0.142- Scalp tenderness31 (31)26 (42.6)0.174- Ocular symptoms14 (14)20 (32.8)0.006- Ischemic optic neuropathy7 (7)17 (27.9)<0.001- Stroke3 (3)0 (0)0.290- Polymyalgia rheumatica42 (42)31 (50.8)0.328- Fever44 (44)12 (19.7)0.002- Fatigue72 (72)21 (34.4)<0.001- Weight loss37 (37)7 (11.5)<0.001- Cough10 (10)1 (1.6)0.053Laboratory findings, mean- C-reactive protein, mg/L80.8 ± 60.865.7 ± 58.20.057- Erythrocyte sedimentation rate76.8 ± 3071.5 ± 270.360- Hemoglobin, g/dL11.4 ± 1.512 ± 1.60.007- Platelet count389.4 ± 116.6366.8 ± 125.20.758Conclusion:LV-GCA patients are younger and suffer of a greater diagnostic delay. Although a greater systemic inflammation seems to be a feature of LV-GCA patients, the vascular prognosis is similar to C-GCA patients, who, conversely, have a greater incidence of ocular complicationsReferences:[1]Dejaco C, et al. Nat Rev Rheumatol (2017)[2]Kermani T, et al. Rheumatology (2019)Disclosure of Interests:Alessandro Tomelleri: None declared, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Silvia Sartorelli: None declared, Nicola Farina: None declared, Elena Baldissera Speakers bureau: Novartis, Pfizer, Roche, Alpha Sigma, Sanofi, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOB

FRI0506 EFFICACY AND SAFETY OF CANAKINUMAB IN ADULT-ONSET STILL'S DISEASE: A SINGLE-CENTER REAL-LIFE EXPERIENCE

Background:The pro-inflammatory cytokine interleukin (IL)-1 has a central role in the pathogenesis of adult-onset Still's disease (AOSD), a rare auto-inflammatory condition. Anakinra, has been for years the cornerstone of IL-1-blocking therapy in AOSD. More recently, the monoclonal antibody canakinumab, a new agent blocking IL-1, has become availableObjectives:To describe our real-life experience with CNK in a cohort of AOSD patients from a single Italian CenterMethods:AOSD patients diagnosed according to Yamaguchi's criteria followed-up at our Autoinflammatory Unit and treated with CNK for at least 3 months were included. Demographic features, disease characteristics, reasons for CNK introduction, concomitant therapies, variation in systemic steroids dose, adverse events, and response to treatment were retrospectively evaluated. Non-parametric tests were used for statistical comparisonResults:13 patients (5 women; median age 49 years, range 21-74), treated with subcutaneous CNK 4 mg/kg 4-weekly, were identified. Median disease duration before CNK introduction was 12 (6-240) months. After CNK introduction, 2 patients were followed-up for 18 months, 3 for 12 months, 6 for 6 months, 2 for 3 months. CNK was introduced as first-line biologic DMARD in 6 patients. The other 7 patients had been already treated with at least one other bDMARD, for a total of 15 treatment courses (7, anakinra, ANK; 4, tocilizumab; 4, TNF-inhibitors), with a median bDMARD therapy duration of 8 (4-178) months. Previous bDMARDs had been interrupted because of inefficacy (8 cases) or adverse events (AE, 7 cases); of the 7 ANK-treated patients, therapy interruption was due to inefficacy in 3 cases. At CNK introduction, 11 patients were on systemic steroid therapy, prednisone (PDN) equivalent dose 15 (5-80) mg, and 10 were concomitantly receiving a conventional DMARD (7, methotrexate; 2, colchicine; 1, cyclosporine-A).Graphic 1summarizes main clinical features at CNK introduction. After CNK start, a striking and rapid clinical response was observed, as demonstrated by a substantial decrease of modified Pouchot score and a normalization of acute phase reactants after only 3 months (see Table 1 for details). CNK showed also a significant steroid-sparing effect: median PDN dose was reduced to 7.5 (2.5-12.5) mg at month 3 and 5 (0-7.5) mg at month 6; PDN was stopped in 3 patients (1 at month 3, 1 at month 6, 1 at month 12) due to optimal disease control. CNK was temporarily held-off in 3 patients (zoster reactivation, 1; prostatitis, 1; mild leukopenia, 1). We observed no case of primary inefficacyTable 1.Disease activity and blood tests at canakinumab introduction and during follow-upDaily prednisone dosemgBaseline(n=13)3 months(n=13)6 months(n=11)12 months(n=5)18 months(n=2)Pouchot score15 (5-80)7.5 (2.5-12.5)5 (0-7.5)5 (0-7.5)2.5VAS pain3 (2-5)1 (0-2)0 (0-1)00Erythrocyte sedimentation ratemm/h7 (2-10)3 (1-8)2 (1-4)1 (1-2)1C-reactive proteinmg/L42 (8-120)21 (2-69)13 (2-55)14 (2-41)11Ferritinng/mL20.8 (3-180)3.1 (0.5-22.5)1.6 (0.5-8.4)1 (0.3-6.3)0.5Hemoglobing/dL379.5 (161-914)282 (82-552)215 (34-464)177 (77-401)19913.1 (9.4-15.7)13.2 (10.7-15.3)13.8 (11.5-15.5)13.9 (11.3-14.3)13.5Figure 1.Graphic 1 Main clinical features at canakinumab introductionConclusion:Our real-life data confirm that CNK is highly effective and safe in AOSD treatment and has significant steroid-sparing effects. CNK showed its efficacy both as first-line therapy and after other bDMARDs failure, also in patients who have previously failed IL-1 inhibition through ANKReferences:[1] Cavalli G, et al. Treating rheumatological diseases and co-morbidities with interleukin-1 blocking therapies. Rheumatology (2015)[2] Cavalli G, et al. Efficacy of Canakinumab as First-Line Biologic Agent in Adult-Onset Still's Disease. Arthritis Res Ther (2019)Disclosure of Interests:Alessandro Tomelleri: None declared, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Giacomo De Luca Speakers bureau: SOBI, Novartis, Celgene, Pfizer, MSD, Nicola Farina: None declared, Elena Baldissera Speakers bureau: Novartis, Pfizer, Roche, Alpha Sigma, Sanofi, Giulio Cavalli Speakers bureau: SOBI, Novartis, Pfizer, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOB

POS1247 CLINICAL FEATURES AND OUTCOMES OF COVID-19 IN PATIENTS WITH IGG4-RELATED DISEASE. A COLLABORATIVE EUROPEAN MULTI-CENTRE STUDY

Background:Coronavirus disease 2019 (COVID-19) is a pandemic-spread systemic infectious disease with prominent respiratory manifestations and significant associated morbidity and mortality. Elderly people are most significantly affected with mortality ranging from 2.4% (age 60-69) to 19.6% (age>80) in European Countries. The prevalence of COVID-19 and of its complications in patients with immune-mediated disorders, remains unclear. The frequency and impact of COVID-19 on patients with IgG4-related diease (IgG4-RD), many of whom are on concurrent immunosuppression has not been addressed.Objectives:To assess the epidemiological and clinical relevance of COVID-19 in patients with IgG4-RD.Methods:This is a multi-centre retrospective observational study of IgG4-RD patients from France, Italy, Spain and the United Kingdom. Demographics, comorbidities, IgG4-RD features, current and past treatment along with COVID-19-suggestive symptoms and COVID-19 diagnoses from February 2020 to January 2021 were recorded by means of direct or phone interviews. Patients with reverse-transcriptase polymerase chain reaction-confirmed (cCOVID) or presumed COVID-19 based on clinical, serological or imaging features (pCOVID) were pooled for analysis (totCOVID) and compared to patients who were not diagnosed with COVID-19. Inter-group comparison of categorical and quantitative variables were performed by using the chi-square test with Fisher's correction and the Mann-Whitney's test respectively. Data are expressed as median (interquartile range) unless otherwise specified.Results:A total of 305 patients [71% males, median age 64 (54-74) years] were studied. Pancreato-biliary disease was the most frequently observed IgG4-RD phenotype (39%). Fifty-one percent of patients were taking corticosteroids at time of interview and 30% were on biological or conventional immunosuppressants. Thirty-two totCOVID cases (23 cCOVID, nine pCOVID) were identified: 11/32 were hospitalised, two needed intensive care and four (13%; 3/4 aged >80 years) died. Having one or more infected family members was a risk factor for COVID-19 in patients with IgG4-RD (OR=19.9; p20mg) or rituximab administration.Conclusion:The prevalence and course of COVID-19 in IgG4-RD patients are similar to those of the general population of the same age, with no evident impact of disease- or treatment-related factors to the basal infectious risk. Effective public health countermeasures might be beneficial for patients with IgG4RD.References:[1]European Centre for Disease Prevention and Control (ECDC): https://covid19-surveillance-report.ecdc.europa.eu/[2]Yang H, Ann Rheum Dis, 2021Disclosure of Interests:Giuseppe Alvise Ramirez: None declared, Marco Lanzillotta: None declared, Mikael Ebbo: None declared, Andreu Fernandez-Codina Consultant of: consulting fees from Atheneum Consulting, Gaia Mancuso: None declared, Fernando Martínez-Valle: None declared, Olimpia Orozco-Galvez: None declared, Nicolas Schleinitz: None declared, Lorenzo Dagna Consultant of: Abbvie, Amgen, Biogen, BristolMyers Squibb, Celltrion, Galapagos, GlaxoSmithKline, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI, Grant/research support from: The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unresctricted research/educational grants from Abbvie, Bristol-Myers Squibb, Celgene, GlaxoSmithKline,Janssen, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi Genzyme, and SOBI, Emma L. Culver: None declared, Emanuel Della Torre: None declare

Trisomic dose of several chromosome 21 genes perturbs haematopoietic stem and progenitor cell differentiation in Down's syndrome

Children with Down's syndrome (DS) have 20–50-fold higher incidence of all leukaemias (lymphoid and myeloid), for reasons not understood. As incidence of many solid tumours is much lower in DS, we speculated that disturbed early haematopoietic differentiation could be the cause of increased leukaemia risk. If a common mechanism is behind the risk of both major leukaemia types, it would have to arise before the bifurcation to myeloid and lymphoid lineages. Using the transchromosomic system (mouse embryonic stem cells (ESCs)) bearing an extra human chromosome 21 (HSA21)) we analyzed the early stages of haematopoietic commitment (mesodermal colony formation) in vitro. We observed that trisomy 21 (T21) causes increased production of haemogenic endothelial cells, haematopoietic stem cell precursors and increased colony forming potential, with significantly increased immature progenitors. Transchromosomic colonies showed increased expression of Gata-2, c-Kit and Tie-2. A panel of partial T21 ESCs allowed us to assign these effects to HSA21 sub-regions, mapped by 3.5 kbp-resolution tiling arrays. The Gata-2 increase on one side, and c-Kit and Tie-2 increases on the other, could be attributed to two different, non-overlapping HSA21 regions. Using human-specific small interfering RNA silencing, we could demonstrate that an extra copy of RUNX1, but not ETS-2 or ERG, causes an increase in Tie-2/c-Kit levels. Finally, we detected significantly increased levels of RUNX1, C-KIT and PU.1 in human foetal livers with T21. We conclude that overdose of more than one HSA21 gene contributes to the disturbance of early haematopoiesis in DS, and that one of the contributors is RUNX1. As the observed T21-driven hyperproduction of multipotential immature precursors precedes the bifurcation to lymphoid and myeloid lineages, we speculate that this could create conditions of increased chance for acquisition of pre-leukaemogenic rearrangements/mutations in both lymphoid and myeloid lineages during foetal haematopoiesis, contributing to the increased risk of both leukaemia types in DS

POS1061 THE ITALIAN PROSPECTIVE SIRENA STUDY: FOCUS ON EARLY PSORIATIC ARTHRITIS COHORT AND GENDER DIFFERENCES

Background:Limited data on early Psoriatic Arthritis (PsA) are available1,2.Objectives:To describe baseline data of PsA patients naive to any DMARDs.Methods:SIRENA study is an Italian, prospective Registry of Spondyloarthritis patients diagnosed according to ASAS criteria and naïve to any DMARDs. Data on demographic and clinical characteristics of PsA cohort were collected and analysed, also by gender.Results:203/350 (58%) subjects included in SIRENA Registry had PsA (mean age 51.9 years) and in 190/203 (94%) CASPAR classification criteria were fulfilled. In 70% of patients the diagnosis was performed within 24 months from symptom onset. At baseline, 194/203 (95.6%) had mainly peripheral manifestations, 74.4% of patients had skin psoriasis, 40% nail psoriasis, 39.3% clinical enthesitis and 25.9% dactylitis. Mean SJC66 and TJC68 were, respectively, 3 and 7.2; mean PhGA was 46.3; 14.7% of patients were in MDA.The higher tender joint count in women (mean TJC68 9.3 in women vs 5.3 in men) resulted in a higher disease activity according to DAPSA (high disease activity: 11.5% women vs 4.1% men), a higher joint VAS score (mean score 47.1 women vs 39.8 men) and a lower prevalence of MDA (8.3% women vs 20% men). We observed a higher prevalence of moderate or severe psoriasis in men (BSA≥3%: 37% men vs 27.8% women) while all PROs collected (PtGA, pain VAS score, sleep VAS score, BASFI, BASDAI, HAQ-DI, WPAI) were worse in women.The most common comorbidities were cardiometabolic (35.5%), endocrine (9.4%), and gastrointestinal disorders (7.4%). Cardiometabolic disorders were more frequently reported by men, endocrine and gastrointestinal disorders by women; depression exclusively by women.Conclusion:This analysis provides real-life data in a cohort of early PsA subjects. Relevant gender differences were observed, with women showing a higher disease activity and more joint pain and men having more severe psoriasis. Women also perceived a worse disease burden.References:[1]Theander E, et al. Ann Rheum Dis 2014; 73:407–413.[2]Nas K, et al. Mod Rheumatol 2017; 27(2):345-349.Table 1.Baseline dataPsAAll patients (n=203)Women (n=98)Men (n=105)Age (years), mean (SD)51.9 (13.1)51.1 (13.2)52.7 (13.0)Men, n (%)105 (51.7)0 (0)105 (100)BMI (kg/m2), mean (SD)25.9 (4.4)25.4 (4.9)26.4 (3.9)BMI categories^, n (%) Obese40 (21.2)20 (22.2)20 (20.2) Overweight44 (23.3)15 (16.7)29 (29.3) Under/normal weight105 (55.6)55 (61.1)50 (50.5)Comorbidities > 5%*, n (%) Cardiometabolic72 (35.5)28 (28.6)44 (41.9) Endocrine disease19 (9.4)15 (15.3)4 (3.8) Gastrointestinal15 (7.4)10 (10.2)5 (4.8) Depression/Anxiety8 (3.9)8 (8.2)0 (0) Hepatic diseases7 (3.5)1 (1.0)6 (5.7)Clinical assessmentCRP (mg/dl), median (min-max)0.40 (0 – 7.12)0.31 (0 - 5.40)0.49 (0 - 7.12)SJC66, mean (SD)3.0 (4.0)3.2 (4.0)2.7 (4.0)TJC68, mean (SD)7.2 (8.8)9.3 (10.3)5.3 (6.6)Dactylitis, n/tot assessed (%)35/135 (25.9)12/63 (19.1)23/72 (31.9)Enthesitis, n/tot assessed (%)66/168 (39.3)39/80 (48.8)27/88 (30.7)Psoriasis skin, n (%)151 (74.4)68 (69.4)83 (79.1)Psoriasis nails, n/tot assessed (%)62/155 (40.0)29/75 (38.7)33/80 (41.3)Fibromyalgia, n (%)6 (3.0)5 (5.2)1 (1.0)VAS, mean (SD) [range: 0-100] PhGA score46.3 (25.8)51.2 (25.4)41.7 (25.4) Joint score43.3 (26.8)47.1 (25.2)39.8 (27.8) Skin score20.3 (24.0)17.8 (23.1)22.6 (24.8)DAPSA, mean (SD)22.3 (14.1)26.8 (15.4)18.7 (11.9)DAPSA categories^, n (%)High disease activity13 (7.4)9 (11.5)4 (4.1)Moderate disease activity83 (47.2)43 (55.1)40 (40.8)Low disease activity71 (40.3)24 (30.8)47 (48.0)Remission9 (5.1)2 (2.6)7 (7.1)MDA°, n (%)23 (14.7)6 (8.3)17 (20.0)BSA categories, n (%) 3-10% (moderate psoriasis)35 (24.6)13 (21.2)22 (27.1) >10% (severe psoriasis)12 (8.5)4 (6.6)8 (9.9)* A patient could report one or more comorbidities. ^The sum does not add up to the total because of some missing values. ° According to Coates et al. (Ann Rheum Dis. 2010;69: 48).Disclosure of Interests:Alen Zabotti: None declared, Michele Maria Luchetti Speakers bureau: Honorary fees for conferences and workshops by Janssen, Abbvie, Novartis, Lilly, Celgene, Pfizer, Carlo Selmi Speakers bureau: Honoraria and/or speaker bureau from AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, Pfizer, Sanofi-Regeneron, Grant/research support from: Research support from Amgen, Janssen, Novartis, Pfizer, Roberta Ramonda Speakers bureau: Honoraria and speaker fees from Novartis, Abbvie, Pfizer, MSD, Janssen, Rosa Daniela Grembiale: None declared, Lorenzo Dagna Consultant of: Consultation honoraria from Abbvie, Amgen, Biogen, Celltrion, GlaxoSmithKline, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI, Salvatore D'Angelo Speakers bureau: Consulting fees and/or speakers bureau from AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Sanofi and UCB, Giacomo Cafaro: None declared, Salvatore De Vita: None declared, Mara Felicetti: None declared, Silvia Marelli Employee of: Janssen-Cilag SpA, Daniela Frigerio Employee of: Janssen-Cilag SpA, Ennio Favalli Speakers bureau: Consulting fees and/or speaking engagements from AbbVie, Bristol-Myers Squibb, Lilly, Merck Sharp & Dohme, Pfizer, Galapagos, Sanofi-Genzyme, and UCB

Efficacy and safety of mavrilimumab in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial

OBJECTIVES: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is implicated in pathogenesis of giant cell arteritis. We evaluated the efficacy of the GM-CSF receptor antagonist mavrilimumab in maintaining disease remission. METHODS: This phase 2, double-blind, placebo-controlled trial enrolled patients with biopsy-confirmed or imaging-confirmed giant cell arteritis in 50 centres (North America, Europe, Australia). Active disease within 6 weeks of baseline was required for inclusion. Patients in glucocorticoid-induced remission were randomly assigned (3:2 ratio) to mavrilimumab 150 mg or placebo injected subcutaneously every 2 weeks. Both groups received a 26-week prednisone taper. The primary outcome was time to adjudicated flare by week 26. A prespecified secondary efficacy outcome was sustained remission at week 26 by Kaplan-Meier estimation. Safety was also assessed. RESULTS: Of 42 mavrilimumab recipients, flare occurred in 19% (n=8). Of 28 placebo recipients, flare occurred in 46% (n=13). Median time to flare (primary outcome) was 25.1 weeks in the placebo group, but the median was not reached in the mavrilimumab group (HR 0.38; 95% CI 0.15 to 0.92; p=0.026). Sustained remission at week 26 was 83% for mavrilimumab and 50% for placebo recipients (p=0.0038). Adverse events occurred in 78.6% (n=33) of mavrilimumab and 89.3% (n=25) of placebo recipients. No deaths or vision loss occurred in either group. CONCLUSIONS: Mavrilimumab plus 26 weeks of prednisone was superior to placebo plus 26 weeks of prednisone for time to flare by week 26 and sustained remission in patients with giant cell arteritis. Longer treatment is needed to determine response durability and quantify the glucocorticoid-sparing potential of mavrilimumab. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number: NCT03827018, Europe (EUdraCT number: 2018-001003-36), and Australia (CT-2018-CTN-01 865-1)

Erdheim-Chester Disease With Multiorgan Involvement, Following Polycythemia Vera : a Case Report

Erdheim-Chester disease is a rare form of non-Langerhans cell histiocytosis characterized by the migration and infiltration of lipid-laden CD68, CD1a and S100 histiocytes to various target organs, which leads to the disruption of physiological tissue architecture and reactive fibrosis, and thus impairs organ function.We describe the first case of a patient with Erdheim-Chester disease with multiorgan involvement developed after 6 years from polycythemia vera diagnosis. During the follow-up, an abdominal ultrasound scan revealed the presence of dense, bilateral perinephric infiltration. A computed tomographic guided core biopsy was performed in order to identify the histological nature of this lesion, and a morphological analysis demonstrated the accumulation of foamy histiocytes surrounded by fibrosis. The BRAFV600E mutation was detected, and a diagnosis of Erdheim-Chester disease was made.The extreme rarity of Erdheim-Chester disease strongly suggests the existence of potentially common element(s) that may have contributed to the pathogenesis of both disorders. Obviously, further studies are needed to clarify the mutual roles and effects of JAK2 and BRAF mutations in this patient, as well as their possible therapeutic implications

The Equity Impact Vaccines May Have On Averting Deaths And Medical Impoverishment In Developing Countries.

With social policies increasingly directed toward enhancing equity through health programs, it is important that methods for estimating the health and economic benefits of these programs by subpopulation be developed, to assess both equity concerns and the programs' total impact. We estimated the differential health impact (measured as the number of deaths averted) and household economic impact (measured as the number of cases of medical impoverishment averted) of ten antigens and their corresponding vaccines across income quintiles for forty-one low- and middle-income countries. Our analysis indicated that benefits across these vaccines would accrue predominantly in the lowest income quintiles. Policy makers should be informed about the large health and economic distributional impact that vaccines could have, and they should view vaccination policies as potentially important channels for improving health equity. Our results provide insight into the distribution of vaccine-preventable diseases and the health benefits associated with their prevention

Effectiveness of Golimumab as Second Anti-TNFα Drug in Patients with Rheumatoid Arthritis, Psoriatic Arthritis and Axial Spondyloarthritis in Italy: GO-BEYOND, a Prospective Real-World Observational Study

In this prospective observational study, data were collected from 34 rheumatology clinics in Italy in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) who started golimumab (GLM) as a second anti-TNFα drug. The primary objective was to evaluate the effectiveness of GLM after 6 months. Changes in quality of life using the EQ-5D-5L were also assessed. A total of 194 patients aged 53.2 ± 12 years started GLM as a second anti-TNF drug: 39 (20.1%) with RA, 91 (46.9%) with PsA and 64 (32.9%) with axSpA. After 6 months of GLM treatment, 68% of RA patients achieved low disease activity (LDA; DAS28-CRP ≤ 3.2), 31.9% of PsA patients achieved minimal disease activity and 32.5% of axSpA patients achieved LDA (ASDAS-CRP &lt; 2.1). Good/moderate EULAR response was achieved in 61.9% and 73.8% of patients with RA and PsA, respectively, and 16% of axSpA patients achieved a 50% improvement in BASDAI. Across all indications, improvements in disease activity measures and EQ-5D-5L domains were observed over 6 months. The main reasons for GLM interruption were lack/loss of efficacy (7.2%) or adverse events (2%). This study confirms the effectiveness of GLM as a second-line anti-TNF for the treatment of RA, PsA and axSpA in a real-world setting in Italy