225 results on '"Ricardo Blanco"'
Search Results
2. Association between cumulative dose of hydroxychloroquine and electrocardiographic abnormalities in patients with systemic lupus erythematosus
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Jon Zubiaur, Alba Herrero-Morant, Adrián Margarida de Castro, Raquel Pérez-Barquín, Ivan Ferraz-Amaro, Javier Loricera, Santos Castañeda, and Ricardo Blanco
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Internal Medicine - Published
- 2023
3. Systemic treatment in sarcoidosis: Experience over two decades
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Raúl Fernández-Ramón, Jorge J. Gaitán-Valdizán, Iñigo González-Mazón, Lara Sánchez-Bilbao, José L. Martín-Varillas, David Martínez-López, Rosalía Demetrio-Pablo, M.Carmen González-Vela, Iván Ferraz-Amaro, Santos Castañeda, Miguel A. González-Gay, and Ricardo Blanco
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Internal Medicine - Abstract
The aim of this study was to evaluate the frequency of systemic treatment in a cohort of sarcoidosis patients and identify presenting clinical features as predictive factors of the need for systemic immunosuppressive therapy.Retrospective study of 342 patients diagnosed and followed-up from January 1999 to December 2019 in a University Hospital in Northern Spain. The diagnosis of sarcoidosis was established according to ATS/ERS/WASOG criteria. A comparative analysis was performed between treated and untreated patients. Predictive factors of treatment prescription according to initial clinical manifestations were identified (multivariate analysis).Mean age at diagnosis was 47.7±15.1 years, with a slight female predominance (51.8%) and Caucasian majority (94.2%). The main clinical manifestation was thoracic involvement (88.3%). Extrathoracic manifestations were detected in 68.4% cases, mainly cutaneous (34.2%), articular (27.8%) and ocular (17.8%). A total of 207 (60.5%) patients required systemic treatment. Glucocorticoid therapy was the most widely used (60.5%). Conventional immunosuppressive therapy in 25.4%, more frequently MTX (21.9%). Biologic therapy was prescribed in 12.9%, especially adalimumab (9.1%). Male gender (OR: 1.65; 95%CI: 1.06-2.56), intrathoracic (OR: 2.41; 95%CI: 1.22-4.76), ocular (OR: 4.14; 95%CI: 2.01-8.52), parotid (OR: 1.60; 95%CI: 1.39-1.94), neurological (OR: 5.00; 95%CI: 1.68-14.84), and renal (OR: 1.59; 95%CI: 1.38-1.94) involvement were identified as risk factors associated with the need of systemic treatment.Most patients (60.5%) of sarcoidosis in our series required systemic therapy. An association between certain characteristics at initial presentation (male gender, lung, ocular, parotid, neurological and renal involvement) and the need of systemic treatment was identified.
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- 2023
4. Epidemiological and genetic features of anti-3‑hydroxy-3-methylglutaryl-CoA reductase necrotizing myopathy: Single-center experience and literature review
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Diana Prieto-Peña, Javier G. Ocejo-Vinyals, Joel Mazariegos-Cano, Ana L. Pelayo-Negro, Sara Remuzgo-Martínez, Fernanda Genre, Alicia García-Dorta, Mónica Renuncio-García, Víctor M. Martínez-Taboada, Carmen García-Ibarbia, Julio Sánchez-Martín, Marcos López-Hoyos, Ricardo Blanco, Miguel A. González-Gay, and José L. Hernández
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Male ,Myositis ,Liver-Specific Organic Anion Transporter 1 ,Middle Aged ,Autoimmune Diseases ,Necrosis ,Hypothyroidism ,Muscular Diseases ,Internal Medicine ,Humans ,Female ,Hydroxymethylglutaryl CoA Reductases ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Vitamin D ,Muscle, Skeletal ,Aged ,Autoantibodies ,HLA-DRB1 Chains - Abstract
To characterize the demographic, genetic, clinical, and serological features of patients with anti-3‑hydroxy-3-methylglutaryl-CoA reductase (HMGCR) immune-mediated necrotizing myopathy (IMNM) in a region of northern Spain.Study of all patients diagnosed with anti-HMGCR IMNM during a 5-year period at a reference hospital in northern Spain. Besides clinical and laboratory data, we analyzed the genetic influence of HLA genes and the rs4149056 (c.521TC) single nucleotide polymorphism (SNP) in the SLCO1B1 gene.8 patients (5 women, 3 men) with a mean ± SD age of 64.9 ± 7.3 years, fulfilled the criteria for anti-HMGCR IMNM. The incidence rate was 0.6 per 100.000 person-years and the prevalence 3 per 100.000 population. All patients had been exposed to statins. All of them had predominant lower limb proximal and symmetric muscle weakness that was severe in 2 and had elevated serum CK levels with a median [IQR] of 4488 [2538-9194] IU/L. Serum 25‑hydroxy vitamin D levels were decreased in all patients in whom it was determined. The 3 patients with a previous diagnosis of hypothyroidism had abnormal levels of TSH at the time of diagnosis. All patients experienced improvement with different schemes of immunosuppressive therapy. Noteworthy, 7 of 8 patients carried the HLA-DRB1*11 allele. The frequency of the rs4149056 C allele in the SLCO1B1 gene (12.5%) was similar to that of the general population.In northern Spain, anti-HMGCR IMNM preferentially affects people over 50 years of age who are carriers of the HLA-DRB1*11 allele and take statins. Both low vitamin D levels and hypothyroidism may play a potential predisposing role in the development of this disease.
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- 2022
5. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 2 trial
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Ahmed M. Soliman, Andrew J. K. Östör, Ann Eldred, Wenjing Lu, Ricardo Blanco, Jacob A. Aelion, Lisa Barcomb, Alan Kivitz, Zailong Wang, Kim A. Papp, Cecilia Asnal, Filip Van den Bosch, and Gabriela Alperovich
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Adult ,Male ,medicine.medical_specialty ,Immunology ,Arthritis ,Placebo ,General Biochemistry, Genetics and Molecular Biology ,THERAPIES ,Double blind ,Young Adult ,Psoriatic arthritis ,Double-Blind Method ,Rheumatology ,Internal medicine ,Medicine and Health Sciences ,medicine ,Clinical endpoint ,Humans ,Immunology and Allergy ,Patient Reported Outcome Measures ,Adverse effect ,Aged ,RISK ,Aged, 80 and over ,Risankizumab ,business.industry ,Arthritis, Psoriatic ,Biology and Life Sciences ,Antibodies, Monoclonal ,Middle Aged ,medicine.disease ,Treatment Outcome ,arthritis ,biological therapy ,Antirheumatic Agents ,Female ,psoriatic ,business - Abstract
ObjectivesRisankizumab is an interleukin-23 inhibitor under study for the treatment of patients with psoriatic arthritis (PsA). The phase 3 KEEPsAKE 2 trial investigated the efficacy and safety of risankizumab versus placebo in patients with active PsA who had previous inadequate response or intolerance to ≤2 biological therapies (Bio-IR) and/or ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR). Results through week 24 are reported here.MethodsAdults with PsA who were Bio-IR and/or csDMARD-IR were randomised to receive subcutaneously administered risankizumab 150 mg or placebo at weeks 0, 4 and 16 during a 24-week, double-blind treatment period. The primary endpoint was the proportion of patients who achieved ≥20% improvement in American College of Rheumatology score (ACR20) at week 24. Secondary endpoints assessed key domains of PsA and patient-reported outcomes.ResultsA total of 444 patients (median age 53 years, range 23–84 years) were randomised to risankizumab (n=224) or placebo (n=220); 206 patients (46.5%) were Bio-IR. At week 24, a significantly greater proportion of patients receiving risankizumab achieved the primary endpoint of ACR20 (51.3% vs 26.5%, pConclusionTreatment with risankizumab resulted in significant improvements versus placebo in key disease outcomes and was well tolerated in patients with PsA who were Bio-IR and/or csDMARD-IR.Trial registration numberNCT03671148.
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- 2021
6. Epidemiology of sarcoidosis in northern Spain, 1999-2019: A population-based study
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Santos Castañeda, L. Sanchez-Bilbao, José M. Cifrián, R. Demetrio-Pablo, Javier Llorca, Ricardo Blanco, Jorge J. Gaitán-Valdizán, M. Carmen González-Vela, Miguel A. González-Gay, José Luis Martín-Varillas, Raúl Fernández-Ramón, and D. Martínez-López
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Adult ,Male ,medicine.medical_specialty ,Pediatrics ,Sarcoidosis ,Population ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Epidemiology ,Internal Medicine ,medicine ,Humans ,030212 general & internal medicine ,education ,Aged ,Retrospective Studies ,Skin ,education.field_of_study ,business.industry ,Incidence ,Incidence (epidemiology) ,Middle Aged ,medicine.disease ,University hospital ,Confidence interval ,Radiography ,Population based study ,Spain ,Cohort ,Female ,business - Abstract
Background The incidence of sarcoidosis varies widely worldwide. The aim of this study was to estimate the incidence of sarcoidosis in a population-based cohort from northern Spain. Methods Patients diagnosed with sarcoidosis at Marques de Valdecilla University Hospital, corresponding to the central Cantabria that encompasses Santander city and the surroundings, between January 1999 and December 2019were assessed. The diagnosis of sarcoidosis was established according to ATS/ERS/WASOG criteria as follows: compatible clinical and radiological presentation, histopathologic confirmation, and exclusion of other granulomatous diseases. Demographic and clinical data were collected. The incidence of sarcoidosis between 1999-2019 was estimated by sex, age, and year of diagnosis. Results A total of 234 patients were included, with a male/female ratio of 0.81. The mean age of the cohort at diagnosis was 48.43 ± 14.83 years and 129 (55.1%) were women. Incidence during the period of study was 3.58 per 100,000 populations (95% confidence interval: 3.13 – 4.07). No gender predominance was observed. An increase in age at diagnosis over time was found in the linear regression analysis. Thoracic affection was found in 180 patients (76.9%). Most common extra-thoracic areas affected were skin (34.2%), joints (30.8%) and eyes (15.4%). Conclusions The incidence of sarcoidosis estimated in this study was similar to that of other Mediterranean countries. No gender predominance was observed. Consistent with previous studies, male presented an incidence peak 10 years earlier than female. A second peak between ages 60-69 years was identified in both sexes.
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- 2021
7. Evaluation of serum omentin-1 and apelin concentrations in patients with hidradenitis suppurativa
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Cristina Mata, Ricardo Blanco, Sandra Guiral, Miguel A. González-Gay, Marcos A. González-López, José L. Hernández, J. Gonzalo Ocejo-Viñals, Alfonso Corrales, Virginia Portilla, Diego Díaz, M. Carmen González-Vela, and Universidad de Cantabria
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medicine.medical_specialty ,Omentin ,Adipokine ,Dermatology ,Pathogenesis ,Insulin resistance ,Adipokines ,Internal medicine ,Immunology and Allergy ,Medicine ,Hidradenitis suppurativa ,Risk factor ,adipokines ,omentin ,Original Paper ,business.industry ,hidradenitis suppurativa ,medicine.disease ,RC31-1245 ,Hidradenitis Suppurativa ,Apelin ,Endocrinology ,apelin ,RL1-803 ,business ,Body mass index ,Homeostasis - Abstract
Introduction: Recent studies suggest a role of adipokines in the pathogenesis of hidradenitis suppurativa (HS). Omentin-1 and apelin are two recently identified adipokines that have been involved in the regulation of metabolic and inflammatory responses. Aim: To investigate serum omentin-1 and apelin levels in patients with HS and to assess their associations with metabolic parameters, disease severity and HS risk. Material and methods: This case-control study included 139 non-diabetic individuals (78 HS patients and 61 ageand sex-matched controls). Serum concentrations of omentin-1 and apelin and the homeostasis model assessment of insulin resistance (HOMA-IR) were measured in all participants. Results: Serum omentin-1 concentrations were significantly higher in HS patients compared to controls, whereas apelin serum levels did not significantly differ between both groups. These differences in omentin-1 concentrations remained significant even after adjusting for age, sex, and body mass index (BMI). The results of logistic regression analysis showed that increased omentin-1 plasma levels were an independent risk factor for HS. However, we found no association between serum levels of both omentin-1 and apelin with HS severity. Conclusions: Our results show that patients with HS have raised omentin-1 serum levels, which are associated with HS risk.
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- 2021
8. Treatment With Tofacitinib in Refractory Psoriatic Arthritis: A National Multicenter Study of the First 87 Patients in Clinical Practice
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Eva, Galíndez-Agirregoikoa, Diana, Prieto-Peña, José Luis, Martín-Varillas, Beatriz, Joven, Olga, Rusinovich, Rafael B, Melero-González, Francisco, Ortiz-Sanjuan, Raquel, Almodóvar, Juan José, Alegre-Sancho, Ángels, Martínez, Agustí, Sellas-Fernández, Lara, Méndez, Rosario, García-Vicuña, Belén, Atienza-Mateo, Iñigo, Gorostiza, Miguel Ángel, González-Gay, Ricardo, Blanco, and María Luz, García-Vivar
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Adult ,Male ,medicine.medical_specialty ,Immunology ,law.invention ,Psoriatic arthritis ,Piperidines ,Rheumatology ,Randomized controlled trial ,Refractory ,Prednisone ,law ,Internal medicine ,Humans ,Immunology and Allergy ,Medicine ,Pyrroles ,Adverse effect ,Tofacitinib ,medicine.diagnostic_test ,business.industry ,Arthritis, Psoriatic ,Middle Aged ,medicine.disease ,Pyrimidines ,Treatment Outcome ,Erythrocyte sedimentation rate ,Female ,Apremilast ,business ,medicine.drug - Abstract
Objective.Tofacitinib (TOF) is the first Janus kinase (JAK) inhibitor approved for psoriatic arthritis (PsA). It has shown efficacy in patients refractory to anti–tumor necrosis factor-α in randomized controlled trials (RCTs). Our aim was to assess efficacy and safety of TOF in clinical practice.Methods.This was an observational, open-label multicenter study of PsA patients treated with TOF due to inefficacy or adverse events of previous therapies. Outcome variables were efficacy, corticosteroid dose-sparing effect, retention rate, and safety. A comparative study of clinical features between our cohort of patients and those from the OPAL Beyond trial was performed.Results.There were 87 patients (28 women/59 men), with a mean age of 52.8 ± 11.4 years. All patients were refractory to biologic disease-modifying antirheumatic drugs (DMARDs) and/or to conventional synthetic DMARDs plus apremilast. TOF was started at 5 mg twice daily after a mean follow-up of 12.3 ± 9.3 years from PsA diagnosis. At first month, Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) decreased from median 4.8 (IQR 4.1–5.4) to 3.7 (IQR 2.8–4.7,P< 0.01), Disease Activity Index for Psoriatic Arthritis from median 28 (IQR 18.4–34.1) to 15.5 (IQR 10.1–25.7,P< 0.01), and C-reactive protein from median 1.9 (IQR 0.3–5.0) to 0.5 (IQR 0.1–2.2) mg/dL (P< 0.01). Also, TOF led to a significant reduction in prednisone dose. Mild adverse effects were reported in 21 patients (24.13%), mainly gastrointestinal symptoms. TOF retention rate at Month 6 was 77% (95% CI 65.2–86.3). Patients in clinical practice were older with longer disease duration and received biologic agents more commonly than those in the OPAL Beyond trial.Conclusion.Data from clinical practice confirm that TOF seems to be effective, rapid, and relatively safe in refractory PsA despite clinical differences with patients in RCTs.
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- 2021
9. Abatacept in monotherapy vs combined in interstitial lung disease of rheumatoid arthritis—multicentre study of 263 Caucasian patients
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Luis Arboleya, Santos Castañeda, Eva Salgado, Miguel A. González-Gay, Gema Bonilla, Francisco Ortiz-Sanjuán, Javier Loricera, Ricardo Blanco, Evelin Cervantes, Sebastián C Rodríguez-García, Iván Ferraz-Amaro, Javier Narváez, Enrique Raya-Alvarez, Ivette Casafont-Solé, Jesús C Fernández, O. Maíz, Cristina Hidalgo-Calleja, C. Fernández-Díaz, María N Alvarez-Rivas, Iván Cabezas, Belén Atienza-Mateo, Rafael Benito Melero-González, C. Ojeda-Garcia, Clara Aguilera-Cros, Alejandra López-Robles, Sabela Fernández, and Ignacio Villa-Blanco
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Male ,musculoskeletal diseases ,medicine.medical_specialty ,High-resolution computed tomography ,interstitial lung disease ,methotrexate ,Gastroenterology ,abatacept ,high-resolution computed tomography ,Abatacept ,Arthritis, Rheumatoid ,FEV1/FVC ratio ,Basal (phylogenetics) ,conventional disease-modifying antirheumatic drugs ,Rheumatology ,Prednisone ,DLCO ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Aged ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Interstitial lung disease ,comorbidity ,Middle Aged ,respiratory system ,medicine.disease ,rheumatoid arthritis ,Methotrexate ,Antirheumatic Agents ,Rheumatoid arthritis ,Drug Therapy, Combination ,Female ,Lung Diseases, Interstitial ,business ,medicine.drug - Abstract
Objective To assess the efficacy and safety of abatacept (ABA) in monotherapy (ABAMONO) vs combined ABA [ABA plus MTX (ABAMTX) or ABA plus non-MTX conventional synthetic DMARDs (csDMARDs) (ABANON-MTX)] in RA patients with interstitial lung disease (ILD) (RA-ILD). Methods This was a restrospective multicentre study of RA-ILD Caucasian patients treated with ABA. We analysed in the three groups (ABAMONO, ABAMTX, ABANON-MTX) the following outcome variables: (i) dyspnoea; (ii) forced vital capacity (FVC) and diffusion capacity of the lung for the carbon monoxide (DLCO); (iii) chest high-resolution CT (HRCT); (iv) DAS28-ESR; (v) CS-sparing effect; and (vi) ABA retention and side-effects. Differences between basal and final follow-up were evaluated. Multivariable linear regression was used to assess the differences between the three groups. Results We studied 263 RA-ILD patients (mean ± s.d. age 64.6 ± 10 years) [ABAMONO (n = 111), ABAMTX (n = 46) and ABANON-MTX (n = 106)]. At baseline, ABAMONO patients were older (67 ± 10 years) and took higher prednisone dose [10 (interquartile range 5–15) mg/day]. At that time, there were no statistically significant differences in sex, seropositivity, ILD patterns, FVC and DLCO, or disease duration. Following treatment, in all groups, most patients experienced stabilization or improvement in FVC, DLCO, dyspnoea and chest HRCT as well as improvement in DAS28-ESR. A statistically significant difference between basal and final follow-up was only found in CS-sparing effect in the group on combined ABA (ABAMTX or ABANON-MTX). However, in the multivariable analysis, there were no differences in any outcome variables between the three groups. Conclusion In Caucasian individuals with RA-ILD, ABA in monotherapy or combined with MTX or with other conventional-DMARDs seems to be equally effective and safe. However, a CS-sparing effect is only observed with combined ABA.
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- 2021
10. Carotid plaques as predictors of cardiovascular events in patients with Rheumatoid Arthritis. Results from a 5-year-prospective follow-up study
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Iván Ferraz-Amaro, Alfonso Corrales, Ricardo Blanco, Santos Castañeda, Miguel A. González-Gay, Belén Atienza-Mateo, Javier Llorca, N. Vegas-Revenga, Virginia Portilla, and Javier Rueda-Gotor
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medicine.medical_specialty ,Population ,Risk Assessment ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Risk Factors ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,education ,Survival analysis ,Retrospective Studies ,030203 arthritis & rheumatology ,education.field_of_study ,business.industry ,Mortality rate ,Hazard ratio ,medicine.disease ,Confidence interval ,Anesthesiology and Pain Medicine ,Cardiovascular Diseases ,Rheumatoid arthritis ,Cardiology ,business ,Follow-Up Studies ,Kidney disease - Abstract
Objective To investigate if the Systematic Coronary Risk Evaluation (SCORE) and the QRISK3 algorithms as well as the carotid ultrasound are useful predictors of cardiovascular (CV) events and death in a prospectively defined population-based rheumatoid arthritis (RA) inception cohort. Methods A set of 327 consecutive RA patients without history of diabetes, chronic kidney disease or CV events were studied by carotid ultrasound between 2012 and 2013. At that time, CV risk was calculated according to the modified EULAR systematic coronary risk evaluation (mSCORE) for RA. A five-year prospective follow-up study was conducted by survival analysis models. The EULAR mSCORE based on the 2015/2016 updated EULAR recommendations and the QRISK3 algorithms were retrospectively tested using baseline data. Results After 1,984.25 patient-years of follow-up, 23 had died and 27 had experienced CV events. Linearized mortality rate was 1.16/100 patient-years (95% confidence interval [CI]: 0.74--1.73). Adjusting for age, gender and disease duration, a model with carotid plaques (Hazard ratio [HR]: 6.10 [95% CI:0.74--50.0]; p = 0.09) and another model with carotid plaques and QRISK3 (HR for carotid plaques: 6.12 [95% CI: 0.74--50.5]; p = 0.09 and HR for each 1% in QRISK3: 1.03 [95% CI: 0.99--1.07], p = 0.11, respectively were the best predictors of death whereas a model with carotid plaques (HR: 5.25 [95% CI:1.41--19.50]; p = 0.01) and another model with carotid plaques and QRISK3 (HR for carotid plaques: 5.13 [95% CI: 1.36--19.3]; p = 0.02 and HR for each 1% in QRISK3: 1.03 [95% CI: 0.99--1.07], p = 0.12, respectively, were the best predictors of CV events. In contrast, the mSCORE was a weaker predictor of the risk of death or CV events. Conclusions The presence of carotid plaques predicts the development of CV events and death in patients with RA. The predictable capacity of carotid plaques and QRISK3 is higher than that of mSCORE in RA patients.
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- 2020
11. Combined use of QRISK3 and SCORE as predictors of carotid plaques in patients with rheumatoid arthritis
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Santos Castañeda, Ricardo Blanco, Diana Prieto-Peña, Iván Ferraz-Amaro, Javier Llorca, N. Vegas-Revenga, Belén Atienza-Mateo, Alfonso Corrales, Javier Rueda-Gotor, Virginia Portilla, Cristina Corrales-Selaya, and Miguel A. González-Gay
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Male ,medicine.medical_specialty ,Population ,Combined use ,030204 cardiovascular system & hematology ,Carotid Intima-Media Thickness ,Arthritis, Rheumatoid ,Continuous variable ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Internal medicine ,Diabetes mellitus ,Odds Ratio ,medicine ,Humans ,Carotid Stenosis ,Pharmacology (medical) ,In patient ,education ,Retrospective Studies ,Ultrasonography ,030203 arthritis & rheumatology ,education.field_of_study ,business.industry ,Middle Aged ,medicine.disease ,Cardiovascular Diseases ,Rheumatoid arthritis ,Diagnostic odds ratio ,Female ,business ,Algorithms ,Kidney disease - Abstract
Objective Because carotid plaques predict the development of cardiovascular events in RA, we aimed to assess if the combined use of the systematic coronary risk evaluation (SCORE) and the QRISK3 algorithms allows for the identification of RA patients with carotid plaques in a defined population-based RA inception cohort. Methods A set of consecutive RA patients without a history of diabetes, chronic kidney disease or cardiovascular events were studied by carotid US between 2012 and 2019. Modified SCORE (mSCORE) for RA based on the 2015/2016 updated EULAR recommendations and QRISK3 algorithms were retrospectively tested using baseline data obtained at the time of the carotid US assessment. Results A total of 466 (54%) of 865 patients had carotid plaques. Using dichotomized QRISK3 and EULAR mSCORE, 73.2% (95% CI: 68.4.8, 77.6) of patients with QRISK ≥ 10% and EULAR mSCORE Conclusions . The combined use of QRISK3 and EULAR mSCORE allows for the identification of most RA patients at high risk of carotid plaques.
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- 2020
12. Switching between Janus kinase inhibitor upadacitinib and adalimumab following insufficient response: efficacy and safety in patients with rheumatoid arthritis
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Glen T D Thomson, In-Ho Song, Stephen Hall, Ricardo Blanco, Filip Van den Bosch, Louis Bessette, Cristiano A. F. Zerbini, Ryan DeMasi, Yihan Li, Roy Fleischmann, Jeffrey Enejosa, and Y. Song
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medicine.medical_specialty ,rheumatoid ,tumor necrosis factor inhibitors ,Immunology ,Arthritis ,Rheumatoid Arthritis ,Placebo ,General Biochemistry, Genetics and Molecular Biology ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Rheumatology ,Internal medicine ,Medicine and Health Sciences ,therapeutics ,Adalimumab ,medicine ,Humans ,Janus Kinase Inhibitors ,Immunology and Allergy ,In patient ,030212 general & internal medicine ,Adverse effect ,outcome assessment ,Janus kinase inhibitor ,030203 arthritis & rheumatology ,business.industry ,medicine.disease ,health care ,Response efficacy ,Methotrexate ,Treatment Outcome ,arthritis ,Antirheumatic Agents ,Rheumatoid arthritis ,business ,Heterocyclic Compounds, 3-Ring ,medicine.drug - Abstract
ObjectivesTo evaluate efficacy and safety of immediate switch from upadacitinib to adalimumab, or vice versa, in patients with rheumatoid arthritis with non-response or incomplete-response to the initial therapy.MethodsSELECT-COMPARE randomised patients to upadacitinib 15 mg once daily (n=651), placebo (n=651) or adalimumab 40 mg every other week (n=327). A treat-to-target study design was implemented, with blinded rescue occurring prior to week 26 for patients who did not achieve at least 20% improvement in both tender and swollen joint counts (‘non-responders’) and at week 26 based on Clinical Disease Activity Index (CDAI) >10 (‘incomplete-responders’) without washout.ResultsA total of 39% (252/651) and 49% (159/327) of patients originally randomised to upadacitinib and adalimumab were rescued to the alternate therapy. In both switch groups (adalimumab to upadacitinib and vice versa) and in non-responders and incomplete-responders, improvements in disease activity were observed at 3 and 6 months following rescue. CDAI low disease activity was achieved by 36% and 47% of non-responders and 45% and 58% of incomplete-responders switched to adalimumab and upadacitinib, respectively, 6 months following switch. Overall, approximately 5% of rescued patients experienced worsening in disease activity at 6 months postswitch. The frequency of adverse events was similar between switch groups.ConclusionsThese observations support a treat-to-target strategy, in which patients who fail to respond initially (or do not achieve sufficient response) are switched to a therapy with an alternate mechanism of action and experience improved outcomes. No new safety findings were observed despite immediate switch without washout.
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- 2020
13. Improvement of Signs and Symptoms of Nonradiographic Axial Spondyloarthritis in Patients Treated With Secukinumab: Primary Results of a Randomized, Placebo‐Controlled Phase III Study
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Ricardo Blanco, Sibylle Haemmerle, Anna Wiksten, Atul Deodhar, Stephen Hall, Eva Dokoupilova, Denis Poddubnyy, Hideto Kameda, Jürgen Braun, Hanno B. Richards, Marleen G H van de Sande, Alan Kivitz, Brian Porter, Clinical Immunology and Rheumatology, and AII - Inflammatory diseases
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Adult ,Male ,medicine.medical_specialty ,Immunology ,Full Length ,Placebo ,Antibodies, Monoclonal, Humanized ,Loading dose ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Randomized controlled trial ,law ,Internal medicine ,Spondyloarthritis ,Clinical endpoint ,Immunology and Allergy ,Medicine ,media_common.cataloged_instance ,Humans ,030212 general & internal medicine ,Axial spondyloarthritis ,European union ,media_common ,030203 arthritis & rheumatology ,business.industry ,Middle Aged ,Clinical trial ,Treatment Outcome ,Antirheumatic Agents ,Spondylarthropathies ,Secukinumab ,Female ,business - Abstract
Objective: To report the primary (1-year) results from PREVENT, the first phase III study evaluating secukinumab in patients with active nonradiographic axial spondyloarthritis (SpA). Methods: A total of 555 patients were randomized (1:1:1) to receive subcutaneous secukinumab 150 mg with a loading dose (loading dose [LD] group), secukinumab 150 mg without a loading dose (non–loading dose [NL] group), or placebo weekly and then every 4 weeks starting at week 4. The NL group received placebo at weeks 1, 2, and 3 to maintain blinding. Switch to open-label secukinumab or standard of care was permitted after week 20. The study had 2 independent analysis plans, per European Union and non-US (plan A; week 16) and US (plan B; week 52) regulatory requirements. The primary end point was 40% improvement in disease activity according to the Assessment of SpondyloArthritis international Society (ASAS40) criteria at week 16 (in the LD group) and at week 52 (in the NL group) in tumor necrosis factor inhibitor (TNFi)–naive patients. Safety analyses included all patients who received ≥1 dose of study treatment. Results: Overall, 481 patients completed 52 weeks of treatment, including 84.3% (156 of 185) in the LD group, 89.7% (165 of 184) in the NL group, and 86.0% (160 of 186) in the placebo group. The proportion of patients who switched to open-label or standard of care between weeks 20 and 48 was 50.8% in the LD group, 47.3% in the NL group, and 64.0% in the placebo group. Both primary and all secondary end points were met at week 16. The proportion of TNFi-naive patients who met ASAS40 was significantly higher for LD at week 16 (41.5%) and NL at week 52 (39.8%) versus placebo (29.2% at week 16 and 19.9% at week 52; both P < 0.05). No new safety findings were reported. Conclusion: Our findings indicate that secukinumab 150 mg provides significant and sustained improvement in signs and symptoms of nonradiographic axial SpA through 52 weeks. Safety was consistent with previous reports.
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- 2020
14. Efficacy and Safety of Upadacitinib Monotherapy in Methotrexate-Naive Patients With Moderately-to-Severely Active Rheumatoid Arthritis (SELECT-EARLY)
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Ronald F van Vollenhoven, Aileen L. Pangan, Tsutomu Takeuchi, Ricardo Blanco, Vibeke Strand, Maureen Rischmueller, Su Chen, Mohamed-Eslam F. Mohamed, Ricardo Machado Xavier, Alan Friedman, Rheumatology, AII - Inflammatory diseases, Clinical Immunology and Rheumatology, AMS - Amsterdam Movement Sciences, and AMS - Musculoskeletal Health
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Adult ,Male ,medicine.medical_specialty ,Patients ,Active Comparator ,Immunology ,Arthritis ,Rheumatoid Arthritis ,Artrite reumatóide ,Gastroenterology ,law.invention ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Rheumatology ,Randomized controlled trial ,law ,Internal medicine ,Segurança do paciente ,medicine ,Humans ,Immunology and Allergy ,030212 general & internal medicine ,Adverse effect ,Aged ,030203 arthritis & rheumatology ,business.industry ,Middle Aged ,medicine.disease ,Clinical trial ,Treatment Outcome ,Methotrexate ,Antirheumatic Agents ,Rheumatoid arthritis ,Disease Progression ,Female ,Original Article ,Safety ,Eficácia ,business ,Heterocyclic Compounds, 3-Ring ,Tratamento farmacológico ,medicine.drug - Abstract
Objective: The SELECT-EARLY trial was undertaken to study the effect of upadacitinib, an oral, reversible Janus kinase 1–selective inhibitor, as monotherapy in patients with predominantly early rheumatoid arthritis who were naive for or had limited exposure to methotrexate (MTX). Methods: Patients (n = 947) were randomized 1:1:1 to receive once-daily doses of upadacitinib 15 mg or 30 mg or weekly MTX (7.5–20 mg/week) for 24 weeks. The primary end points were the proportion of patients who met the American College of Rheumatology 50% (ACR50) improvement criteria at week 12, and the proportion in whom a Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) of
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- 2020
15. Development of an application for mobile phones (App) based on the collaboration between the Spanish Society of Rheumatology and Spanish Society of Family Medicine for the referral of systemic autoimmune diseases from primary care to rheumatology
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María Medina-Abellán, Juan José Alegre-Sancho, Ana Urruticoechea-Arana, Juan Carlos Hermosa-Hernán, Jose Luis Andreu-Sanchez, Xavier Mas-Garriga, José Andrés Román-Ivorra, Mercedes Freire-González, Fernando León-Vázquez, E. Beltrán-Catalán, Tatiana Cobo-Ibáñez, Jordi Forcada-Gisbert, Ricardo Blanco-Vela, Francisco Vargas-Negrín, Vicente Giner-Ruiz, Carmen Costa-Ribas, María Victoria Hernández-Miguel, Enrique Nieto-Pol, José M. Pego-Reigosa, Alejandro Olivé-Marqués, Iñigo Rúa-Figueroa, Santiago Muñoz-Fernández, Jaime Calvo-Alén, Javier Narváez-García, and Álvaro Pérez-Martín
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medicine.medical_specialty ,Clinical signs ,Referral ,Physical examination ,Primary care ,Autoimmune Diseases ,03 medical and health sciences ,Systemic lupus erythematosus ,0302 clinical medicine ,Rheumatology ,Internal medicine ,Acute phase reactants, Anticuerpos antinucleares, Antinuclear antibodies, Arthralgia, Arthritis, Artralgia, Artritis, Assistance coordination, Atención primaria de salud, Clinical signs, Coordinación asistencial, Derivación y consulta, Enfermedades autoinmunes, Lupus eritematoso sistémico, Primary health care, Proteínas de fase aguda, Referral, Signos y síntomas, Systemic autoimmune disease, Systemic lupus erythematosus ,Humans ,Medicine ,030212 general & internal medicine ,Referral and Consultation ,Societies, Medical ,Primary health care ,Assistance coordination ,030203 arthritis & rheumatology ,Anamnesis ,Primary Health Care ,medicine.diagnostic_test ,business.industry ,Arthritis ,General Medicine ,Laboratory results ,Mobile Applications ,Arthralgia ,Acute phase reactants ,Systemic autoimmune disease ,Antinuclear antibodies ,Family medicine ,Family doctors ,Interdisciplinary Communication ,Family Practice ,business ,Cell Phone ,Abnormal laboratory findings - Abstract
Management of systemic autoimmune diseases is challenging for physicians in their clinical practice. Although not common, they affect thousands of patients in Spain. The family doctor faces patients with symptoms and non-specific cutaneous, mucous, joint, vascular signs or abnormal laboratory findings at the start of the disease process and has to determine when to refer patients to the specialist. To aid in disease detection and better referral, the Spanish Society of Rheumatology and the Spanish Society of Family Medicine has created a group of experts who selected 26 symptoms, key signs and abnormal laboratory findings which were organized by organ and apparatus. Family doctors and rheumatologists with an interest in autoimmune systemic diseases were selected and formed mixed groups of two that then elaborated algorithms for diagnostic guidelines and referral. The algorithms were then reviewed, homogenized and adapted to the algorithm format and application for cell phone (apps) download. The result is the current Referral document of systemic autoimmune diseases for the family doctor in paper format and app (download). It contains easy-to-use algorithms using data from anamnesis, physical examination and laboratory results usually available to primary care, that help diagnose and refer patients to rheumatology or other specialties if needed. (C) 2019 Elsevier Espana, S.L.U. and Sociedad Espanola de Reumatologia y Colegio Mexicano de Reumatologia. All rights reserved.
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- 2020
16. Biologic therapy in severe and refractory peripheral ulcerative keratitis (PUK). Multicenter study of 34 patients
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Santos Castañeda, Lucía Martínez-Costa, Emma Beltrán, María Álvarez del Buergo, L Domínguez-Casas, Miguel A. González-Gay, Ruth López-González, Esteban Rubio-Romero, Ángel García-Aparicio, Ricardo Blanco, L. Sanchez-Bilbao, N. Vegas-Revenga, José L. Hernández, David Díaz-Valle, Antonio Juan Mas, R. Demetrio-Pablo, Ana Blanco, O. Maíz, and Vanesa Calvo-Río
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Adult ,Male ,medicine.medical_specialty ,Corneal inflammation ,Etanercept ,Biological Factors ,03 medical and health sciences ,Psoriatic arthritis ,chemistry.chemical_compound ,0302 clinical medicine ,Tocilizumab ,Rheumatology ,Internal medicine ,medicine ,Adalimumab ,Humans ,030212 general & internal medicine ,Corneal Ulcer ,Aged ,Aged, 80 and over ,030203 arthritis & rheumatology ,business.industry ,Middle Aged ,medicine.disease ,Infliximab ,Anesthesiology and Pain Medicine ,chemistry ,Rheumatoid arthritis ,Female ,business ,Scleritis ,medicine.drug - Abstract
Purpose We assessed the efficacy and safety of biologic therapy in severe and refractory Peripheral Ulcerative Keratitis (PUK). Design Open-label multicenter study of biologic-treated patients with severe PUK refractory to conventional immunosuppressive drugs. Subjects We studied 34 patients (44 affected eyes) (24 women/10 men; mean age, 55.26±17.4 years). PUK was associated with a well-defined condition in 29 of them (rheumatoid arthritis [n = 20], psoriatic arthritis [n = 2], inflammatory bowel disease [n = 2], Behcet disease [n = 1], granulomatosis with polyangiitis [n = 1], microscopic polyangiitis [n = 1], systemic lupus erythematosus [n = 1] and axial spondyloarthritis [n = 1]). Besides topical and oral systemic glucocorticoids, patients had received: methylprednisolone pulses [n = 9], and conventional immunosuppressive drugs, mainly methotrexate [n = 18], and leflunomide [n = 7]. Eleven patients had required ocular surgery prior to biologic therapy. Methods Following biologic therapy, baseline main outcomes were compared with those found at 1st week, 1st and 6th months and 1st year. Main outcome measures Efficacy and safety of biologic therapy. Efficacy was analyzed by the assessment of corneal inflammation (corneal thinning, central keratolysis and ocular perforation); other causes of ocular surface inflammation (scleritis, episcleritis); intraocular inflammation (uveitis); visual acuity and glucocorticoid sparing effect. Results The first biologic agents used were anti-TNFα drugs (n = 25); adalimumab (n = 16), infliximab (n = 8), etanercept (n = 1), and non-TNFα agents (n = 9); rituximab (n = 7), tocilizumab (n = 1) belimumab (n = 1) and abatacept (n = 1). During the follow-up, switching to a second biologic agent was required in 12 of the 25 (48%) patients treated with anti-TNFα drugs. However, no switching was required in those undergoing biologic therapy different from anti-TNFα agents. The main outcome variables showed a rapid and maintained improvement after a mean follow-up of 23.7 ± 20 months. Major adverse effects were tachyphylaxis, relapsing respiratory infections, supraventricular tachycardia, pulmonary tuberculosis and death, one each. Conclusions Biologic therapy is effective and relatively safe in patients with severe and refractory PUK. Non-anti-TNFα agents appear to be effective in these patients.
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- 2020
17. 5-year efficacy and safety of secukinumab in patients with ankylosing spondylitis: end-of-study results from the phase 3 MEASURE 2 trial
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Helena Marzo-Ortega, Karel Pavelka, Hanno B. Richards, Alan Kivitz, Ricardo Blanco, Martin Cohen, Joachim Sieper, Eumorphia Maria Delicha, Susanne Rohrer, and Anna Stefanska
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Ankylosing spondylitis ,medicine.medical_specialty ,business.industry ,Immunology ,medicine.disease ,Placebo ,Ulcerative colitis ,Rheumatology ,Internal medicine ,Immunology and Allergy ,Medicine ,In patient ,Secukinumab ,Interleukin 17 ,business ,Adverse effect ,BASDAI - Abstract
Summary Background Secukinumab, a fully human monoclonal antibody that directly inhibits interleukin 17A, has shown significant and sustained improvement in the signs and symptoms of ankylosing spondylitis over 3 years in the MEASURE 2 study. We report the 5-year (end-of-study) results of subcutaneous secukinumab 150 mg in the MEASURE 2 study. Methods MEASURE 2 was a phase 3, double-blind, randomised, placebo-controlled, study done in 13 countries and 53 centres. Patients with ankylosing spondylitis who were 18 years of age or older and fulfilled the modified New York criteria were randomly assigned to receive secukinumab (150 mg or 75 mg) or placebo subcutaneously at baseline and weeks 1, 2, and 3, and then every 4 weeks from week 4. At week 16, patients initially given placebo were randomly assigned again (placebo switchers) to receive secukinumab 150 mg or 75 mg. Efficacy results are reported for patients initially randomised to secukinumab 150 mg and those who switched from placebo to secukinumab 150 mg at week 16. An optional dose escalation from secukinumab 75 mg to 150 mg was initiated beginning week 140. We assessed efficacy endpoints at week 260 (5 years), including Assessment of Spondyloarthritis International Society (ASAS) 20 and ASAS 40, inactive disease according to ankylosing spondylitis disease activity score with C-reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASDAI50, Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Functional Index, Short Form-36 Physical Component Summary, and ASAS partial remission. Analyses were stratified by anti-tumour necrosis factor (TNF) status (anti-TNF-naive and anti-TNF inadequate response). The safety analysis included all patients who received one dose or more of secukinumab. We report data as observed without accounting for missing data. The MEASURE 2 study was registered with ClinicalTrials.gov , NCT01649375 . Findings 219 patients were randomly assigned during the trial and 150 (68%) completed 5 years of treatment, including 82 (77%) of 106 patients in the secukinumab 150 mg group and 68 (65%) of 105 in the secukinumab 75 mg group. Efficacy analysis in the secukinumab 150 mg group included 53 patients who completed the study and one additional patient who was assessed in the treatment period weeks 212–260, but did not complete the study. 134 (61%) of 219 patients were anti-TNF-naive and 85 (39%) were anti-TNF inadequate responders. ASAS responses at 5 years with secukinumab 150 mg were 36 (67%) of 54 patients (ASA20) and 27 (50%) patients (ASAS40). Sustained improvement was observed across other efficacy endpoints with secukinumab 150 mg at 5 years. At 5 years, the proportion of patients achieving efficacy endpoints of BASDAI 50 response was 53% (44/83); ASAS 5/6 response was 51% (42/83); ASDAS-CRP inactive disease was 21% (17/81); and ASAS partial remission was 25% (21/83). Exposure-adjusted incidence rates with any secukinumab dose for selected adverse events were 1·0 per 100 patient-years (95% CI 0·4–1·9) for Candida infections, 0·5 (0·1–1·2) for Crohn's disease, 0·4 (0·1–1·1) for ulcerative colitis, 0·6 (0·2–1·4) for major adverse cardiovascular events, 0·5 (0·1–1·2) for uveitis, and 0·6 (0·2–1·4) for malignant or unspecified tumours. Interpretation Secukinumab 150 mg provided sustained improvement in the signs, symptoms, and physical function in patients with ankylosing spondylitis after 5 years of treatment. The safety profile of secukinumab remained consistent with previous reports. Funding Novartis Pharma.
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- 2020
18. Secukinumab 150/300 mg Provides Sustained Improvements in the Signs and Symptoms of Active Ankylosing Spondylitis: 3‐Year Results from the Phase 3 <scp>MEASURE</scp> 3 Study
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Karel Pavelka, Alan J. Kivitz, Eva Dokoupilova, Ricardo Blanco, Marco Maradiaga, Hasan Tahir, Yi Wang, Brian O. Porter, Anna Stefanska, Hanno B. Richards, Susanne Rohrer, and the MEASURE 3 study group
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medicine.medical_specialty ,Ankylosing spondylitis ,lcsh:Diseases of the musculoskeletal system ,business.industry ,Outcome measures ,Signs and symptoms ,Original Articles ,Placebo ,medicine.disease ,Disease activity ,Safety profile ,Rheumatology ,Internal medicine ,medicine ,Original Article ,Secukinumab ,lcsh:RC925-935 ,business ,Inactive disease - Abstract
Objective Secukinumab 150 mg has demonstrated significant improvement in signs and symptoms of ankylosing spondylitis (AS), with response rates sustained for up to 5 years. Here, we report end-of-study 3-year efficacy and safety results of secukinumab 150 and 300 mg from the MEASURE 3 study. Methods A total of 226 patients was randomized to intravenous secukinumab 10 mg/kg (baseline, weeks 2 and 4) followed by subcutaneous (s.c.) secukinumab 300/150 mg every 4 weeks or a matched placebo. At week 16, placebo patients were re-randomized to s.c. secukinumab 300/150 mg. Analysis at week 156 included patients initially randomized to secukinumab and those who switched from placebo to secukinumab at week 16 (any secukinumab 300/150 mg). Outcome measures at week 156 included Assessment of Spondyloarthritis International Society (ASAS) 20/40, Bath Ankylosing Spondylitis Disease Activity Index, ASAS partial remission (PR), ASAS 5/6, and Ankylosing Spondylitis Disease Activity Score-C-reactive protein inactive disease. Results The retention rates from weeks 16 to 156 were 80.5% and 80.9% in secukinumab 300 and 150 mg, respectively. ASAS 20/40 response rates at week 156 were 75.0%/56.5% and 68.2%/47.7% for secukinumab 300 and 150 mg, respectively. At week 156, response rates on more stringent clinical end points (eg, ASAS 40, ASAS-PR) were higher with the 300-mg dose, particularly in tumor necrosis factor (TNF)-inadequate responder (IR) patients. No new safety findings were observed. Conclusion Secukinumab (300 and 150 mg) provided sustained improvements through 3 years in the signs and symptoms of active AS. Improvements with secukinumab 300 mg were numerically higher compared with the 150-mg dose for some higher hurdle end points and in TNF-IR patients. The safety profile of secukinumab was consistent with previous reports.
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- 2020
19. Circulating levels of adiponectin, leptin, resistin and visfatin in non-diabetics patients with hidradenitis suppurativa
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M Genma Pérez-Paredes, Sandra Guiral, Marcos A. González-López, Virginia Portilla, Gonzalo Ocejo-Viñals, José L. Hernández, Alfonso Corrales, Iñigo Navarro, Cristina Mata, I. Vilanova, Ricardo Blanco, Rubén Arlegui, Miguel A. González-Gay, and M. Carmen González-Vela
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Adult ,Leptin ,Male ,medicine.medical_specialty ,Adipokine ,Dermatology ,Severity of Illness Index ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Risk Factors ,Internal medicine ,Humans ,Medicine ,Resistin ,Hidradenitis suppurativa ,Nicotinamide Phosphoribosyltransferase ,Adiponectin ,business.industry ,nutritional and metabolic diseases ,General Medicine ,Middle Aged ,medicine.disease ,Hidradenitis Suppurativa ,Cross-Sectional Studies ,Endocrinology ,Case-Control Studies ,030220 oncology & carcinogenesis ,Cytokines ,Female ,Insulin Resistance ,Metabolic syndrome ,business ,Body mass index ,Biomarkers ,hormones, hormone substitutes, and hormone antagonists - Abstract
Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with insulin resistance (IR), metabolic syndrome and increased cardiovascular risk. Adipokines are biologically active, pleotropic molecules which have been involved in the development of IR and in the pathogenesis of several chronic inflammatory conditions. The aim of the present study was to analyze serum concentrations of adiponectin, leptin, resistin and visfatin in patients with HS, and investigate their possible associations with IR, HS risk and disease severity. This case-control study enrolled 137 non-diabetic individuals (76 HS-patients and 61 age and sex-matched controls). Serum concentrations of adiponectin, leptin, resistin and visfatin, and the homeostasis model assessment of IR (HOMA-IR) were measured in all the participants. Serum adiponectin concentrations were found to be significantly lower, and leptin, resistin and visfatin levels were significantly higher in HS-patients than in controls. These differences remained significant even after adjusting for age, sex and body mass index, except for leptin. In a multivariate regression analysis, HOMA-IR was inversely correlated with adiponectin and positively associated with resistin levels. Furthermore, serum levels of resistin and visfatin were independently associated with HS risk. However, we found no association between serum levels of adipokines and HS severity. Our results suggest that reduced adiponectin and increased resistin serum levels may be surrogate biomarkers for IR in patients with HS. Moreover, resistin and visfatin might be independent risk factors for the development of HS.
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- 2019
20. Moderate and High Disease Activity Predicts the Development of Carotid Plaque in Rheumatoid Arthritis Patients without Classic Cardiovascular Risk Factors: Six Years Follow-Up Study
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Diana Prieto-Peña, Miguel A. González-Gay, Alfonso Corrales, Belén Atienza-Mateo, Iván Ferraz-Amaro, Ricardo Blanco, N. Vegas-Revenga, and Universidad de Cantabria
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rheumatoid arthritis ,medicine.medical_specialty ,carotid plaque ,Disease ,Gastroenterology ,Article ,Disease activity ,Internal medicine ,Medicine ,Rrheumatoid arthritis ,Prospective cohort study ,business.industry ,Incidence (epidemiology) ,Cancer ,General Medicine ,Odds ratio ,medicine.disease ,Carotid plaque ,Rheumatoid arthritis ,Prospective Study ,business ,Kidney disease ,prospective study - Abstract
Patients with rheumatoid arthritis (RA) have a higher incidence of subclinical atherosclerosis and cardiovascular (CV) disease. It is postulated that the appearance of accelerated atherosclerosis in these patients is a consequence of the inflammation present in the disease. In this study, we aim to determine if baseline disease activity in patients with RA predicts the future development of carotid plaque. A set of consecutive RA patients without a history of CV events, cancer or chronic kidney disease, who did not show carotid plaque in a carotid ultrasound assessment, were prospectively followed up for at least 5 years. At the time of recruitment, CV risk factors and disease-related data, including disease activity scores, were assessed. At the end of the follow-up, a carotid ultrasound was repeated and patients were divided into two groups, those who developed carotid plaque, and those who did not. A multivariable regression analysis was performed to define the predictors for the development of carotid plaque. One hundred and sixty patients with RA were followed up for an average of 6 ± 1 years. After this time, 66 (41%) of the patients had developed carotid plaque, and 94 (59%) did not. Patients with carotid plaque were significantly older (47 ± 13 vs. 55 ± 9 years, p <, 0.001) at baseline, were more frequently diabetic (0% vs. 6%, p = 0.028), and had higher total cholesterol (197 ± 36 vs. 214 ± 40 mg/dL, p = 0.004) and LDL cholesterol (114 ± 35 vs. 126 ± 35 mg/dL, p = 0.037) at the beginning of the study. After multivariable adjustment, patients who were in the moderate and high disease activity (DAS28-CRP) categories displayed a higher odds ratio for the appearance of carotid plaque (OR 2.26 [95% CI 1.02–5.00], p = 0.044) compared to those in the DAS-28-CRP remission category. Remarkably, when patients were divided in patients within the low-risk SCORE category, and patients included in the remaining SCORE categories (moderate, high and very high), the relation between DAS28-CRP and the development of carotid plaque was only significant in the low-risk SCORE category. In conclusion, disease activity predicts the future development of subclinical atherosclerosis in patients with RA.
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- 2021
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21. Angiogenic T cells in interstitial lung diseases
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Ricardo Blanco, Diana Prieto-Peña, Belén Atienza-Mateo, Alfonso Corrales, Raquel Pérez-Fernández, Fernanda Genre, Pilar Alonso-Lecue, Virginia Portilla, David Iturbe-Fernández, Miguel A. González-Gay, Raquel López-Mejías, José M. Cifrián, Leticia Lera-Gómez, Javier Rodríguez-Carrio, Víctor M. Mora-Cuesta, Sara Remuzgo-Martínez, and Verónica Pulito-Cueto
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CD31 ,medicine.medical_specialty ,Lung ,business.industry ,medicine.medical_treatment ,Venous blood ,respiratory system ,Revascularization ,medicine.disease ,behavioral disciplines and activities ,Gastroenterology ,Connective tissue disease ,CXCR4 ,respiratory tract diseases ,body regions ,Pathogenesis ,Idiopathic pulmonary fibrosis ,medicine.anatomical_structure ,Internal medicine ,medicine ,business - Abstract
Background: Interstitial lung diseases (ILD) lead to an increase in the patient’s morbidity and mortality. According to the etiology, ILD can be divided in disorders with either an unknown or known possible cause such as an underlying connective tissue disease (CTD) [1]. A specific T cell subset termed angiogenic T cells (TAng), that promote endothelial repair and revascularization, has been involved in the pathogenesis of CTD [2]. Nevertheless, little is known about their role in ILD. Objective: To assess the potential role of TAng in ILD. Methods: Peripheral venous blood was collected from 61 patients with ILD (composed of 21 with idiopathic pulmonary fibrosis (IPF) and 40 with CTD-ILD+), 44 CTD-ILD- patients and 20 healthy controls (HC). Quantification of TAng was performed by flow cytometry. TAng were considered as triple-positive for CD3, CD31 and CXCR4. Results: Patients with ILD exhibited a significantly lower TAng frequency than CTD-ILD- patients and HC (mean ± standard deviation: 11.98 ± 4.75 versus 16.24 ± 5.03 and 11.98 ± 4.75 versus 16.50 ± 4.83, respectively, p Conclusion: Our results disclose a decrease of TAng frequency related to the presence of ILD. References: [1] J Clin Med 2020;9(6):1606; [2] Ann Rheum Dis 2015 74(5):921-7. Personal funds, VP-C: PREVAL18/01 (IDIVAL); SR-M: RD16/0012/0009 (ISCIII-ERDF); LL-G: INNVAL20/06 (IDIVAL); RP-F: START PROJECT (FOREUM); RL-M: Miguel Servet type I CP16/00033 (ISCIII-ESF).
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- 2021
22. Secukinumab in non-radiographic axial spondyloarthritis: subgroup analysis based on key baseline characteristics from a randomized phase III study, PREVENT
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Ricardo Blanco, Sibylle Haemmerle, Atul Deodhar, Hideto Kameda, Stephen Hall, Marleen G H van de Sande, Helena Marzo-Ortega, Jürgen Braun, Denis Poddubnyy, Abhijit Shete, Anna Wiksten, Brian Porter, Hanno B. Richards, Lianne S. Gensler, Filip Van den Bosch, Clinical Immunology and Rheumatology, and AII - Inflammatory diseases
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Male ,Diseases of the musculoskeletal system ,Gastroenterology ,Etanercept ,DOUBLE-BLIND ,Medicine and Health Sciences ,EPIDEMIOLOGY ,PREDICTORS ,HLA-B27 Antigen ,Human leukocyte antigen ,biology ,Treatment Outcome ,TRIAL ,Female ,MRI ,medicine.drug ,Research Article ,medicine.medical_specialty ,Magnetic ,Subgroup analysis ,Biologicals ,Placebo ,Antibodies, Monoclonal, Humanized ,Loading dose ,C-reactive protein ,Magnetic resonance imaging ,Internal medicine ,Spondylarthritis ,ETANERCEPT ,medicine ,Humans ,Spondylitis, Ankylosing ,Non-radiographic axial spondyloarthritis ,Human leukocyte antigen B27 ,Ankylosing spondylitis ,HLA-B27 ,resonance imaging ,business.industry ,Interleukins ,Biology and Life Sciences ,Gender ,EFFICACY ,medicine.disease ,RC925-935 ,biology.protein ,Secukinumab ,B27 ,business - Abstract
Background To investigate the efficacy of secukinumab in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) grouped by disease activity as assessed by C-reactive protein (CRP) levels and/or magnetic resonance imaging (MRI) scores, human leukocyte antigen (HLA)-B27 status, and sex. Methods The phase III PREVENT study randomized (1:1:1) 555 patients to receive subcutaneous secukinumab 150 mg with (LD) or without (NL) loading dose or placebo weekly, followed by every 4 weeks starting at week 4. Here, we report the results of a post hoc analysis reporting the efficacy outcomes (pooled secukinumab) to 16 weeks by CRP, MRI, HLA-B27, and sex. Results Efficacy differences between the secukinumab and the placebo groups were highest in the CRP+, MRI+, HLA-B27+, and male subgroups, particularly for Ankylosing Spondylitis Disease Activity Score-CRP inactive disease and Assessment of SpondyloArthritis international Society (ASAS) partial remission outcomes. ASAS40 response rates in the CRP+/MRI+ subgroup was 52.3% (secukinumab) versus 21.8% (placebo; P < 0.0001) at week 16. ASAS40 response rates (secukinumab versus placebo) were 43.9% versus 32.6% in HLA-B27+, 32.7% versus 16.4% in HLA-B27− subgroups, 51.2% versus 30.8% in male, and 31.7% versus 25.3% in female patients, respectively. Conclusions Secukinumab improved the signs and symptoms of nr-axSpA across patients grouped by CRP (+/−) and/or MRI (+/−) status, HLA-B27 (+/−) status, and sex. The highest treatment differences between secukinumab and placebo were observed in patients with both elevated CRP and evidence of sacroiliitis on MRI. Treatment difference was minimal between HLA-B27 (+) and (−) subgroups. Male patients had higher relative responses than female patients. Trial registration ClinicalTrials.gov, NCT02696031. Registered on 02 March 2016
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- 2021
23. Imaging Tests in the Early Diagnosis of Giant Cell Arteritis
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Diana Prieto-Peña, Santos Castañeda, Ricardo Blanco, Miguel A. González-Gay, Isabel Martínez-Rodríguez, Belén Atienza-Mateo, and Universidad de Cantabria
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Positron emission tomography ,medicine.medical_specialty ,positron emission tomography ,Computed tomography ,Review ,Imaging ,immune system diseases ,Internal medicine ,Ultrasound ,medicine ,In patient ,cardiovascular diseases ,skin and connective tissue diseases ,Giant cell arteritis ,medicine.diagnostic_test ,business.industry ,giant cell arteritis ,ultrasound ,imaging ,Magnetic resonance imaging ,computed tomography ,General Medicine ,medicine.disease ,Rheumatology ,cardiovascular system ,Medicine ,Temporal artery ,Radiology ,business ,Rheumatism - Abstract
Early recognition of giant cell arteritis (GCA) is crucial to avoid the development of ischemic vascular complications, such as blindness. The classic approach to making the diagnosis of GCA is based on a positive temporal artery biopsy, which is among the criteria proposed by the American College of Rheumatology (ACR) in 1990 to classify a patient as having GCA. However, imaging techniques, particularly ultrasound (US) of the temporal arteries, are increasingly being considered as an alternative for the diagnosis of GCA. Recent recommendations from the European League Against Rheumatism (EULAR) for the use of imaging techniques for large vessel vasculitis (LVV) included US as the first imaging option for the diagnosis of GCA. Furthermore, although the ACR classification criteria are useful in identifying patients with the classic cranial pattern of GCA, they are often inadequate in identifying GCA patients who have the extracranial phenotype of LVV. In this sense, the advent of other imaging techniques, such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET)/CT, has made it possible to detect the presence of extracranial involvement of the LVV in patients with GCA presenting as refractory rheumatic polymyalgia without cranial ischemic manifestations. Imaging techniques have been the key elements in redefining the diagnostic work-up of GCA. US is currently considered the main imaging modality to improve the early diagnosis of GCA.
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- 2021
24. High prevalence of non‐alcoholic fatty liver disease among hidradenitis suppurativa patients independent of classic metabolic risk factors
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M González, Javier Crespo, Marcos A. González-López, V Fernández, Ricardo Blanco, José P. Vaqué, Paula Iruzubieta, José L. Hernández, C Durán-Vian, María Teresa Arias-Loste, Laura Rasines, and Carmen González-Vela
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Adult ,Male ,medicine.medical_specialty ,Dermatology ,Disease ,Chronic liver disease ,Gastroenterology ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Metabolic Diseases ,Non-alcoholic Fatty Liver Disease ,Risk Factors ,Internal medicine ,Psoriasis ,Prevalence ,Humans ,Medicine ,Hidradenitis suppurativa ,business.industry ,Fatty liver ,Case-control study ,nutritional and metabolic diseases ,Middle Aged ,medicine.disease ,digestive system diseases ,Hidradenitis Suppurativa ,Infectious Diseases ,Case-Control Studies ,Female ,030211 gastroenterology & hepatology ,business ,Transient elastography - Abstract
BACKGROUND Some chronic inflammatory skin diseases, such as psoriasis, have been associated with an increased prevalence of non-alcoholic fatty liver disease (NAFLD). Nevertheless, this prevalence in hidradenitis suppurativa (HS) has not been assessed to date. OBJECTIVES To determine the prevalence of NAFLD in patients with HS and the risk factors associated with this disorder. METHODS This case-control study enrolled 70 HS patients and 150 age- and gender-matched controls who were evaluated by hepatic ultrasonography (US) and transient elastography (TE) after excluding other secondary causes of chronic liver disease. The diagnosis of NAFLD was established if US and/or TE were altered. RESULTS The prevalence of NAFLD was significantly increased in patients with HS compared to controls (72.9% vs. 24.7%: P
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- 2019
25. Predicting the risk of relapse in polymyalgia rheumatica: novel insights
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Ricardo Blanco, Belén Atienza-Mateo, Miguel A. González-Gay, Diana Prieto-Peña, and Santos Castañeda
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musculoskeletal diseases ,medicine.medical_specialty ,Shoulders ,education ,Immunology ,Disease ,European descent ,Polymyalgia rheumatica ,immune system diseases ,Prednisone ,Recurrence ,Risk Factors ,Internal medicine ,medicine ,Immunology and Allergy ,Humans ,Relapse risk ,skin and connective tissue diseases ,business.industry ,medicine.disease ,Giant cell arteritis ,Polymyalgia Rheumatica ,Methotrexate ,business ,medicine.drug - Abstract
Polymyalgia rheumatica (PMR) is a common inflammatory disease found in people older than 50 years of Northern European descent. It is characterized by pain and stiffness in the shoulders, arms, hips, and neck. Relapses are common in patients with PMR.This review describes when and how relapses occur in patients with PMR. Potential predisposing factors associated with relapses and management are also discussed. An extensive literature search on the PubMed database was conducted for publications on 'polymyalgia rheumatica' AND 'relapses' AND 'risk factors'.Relapses are common in PMR being observed in approximately half of the patients. They often occur when the dose of prednisone is below 5-7.5 mg/day. The speed of glucocorticoid tapering is considered to be the main factor influencing the development of relapses in isolated PMRs. In addition, a genetic component may favor the presence of relapses in isolated PMRs. HLA-DRB1*0401 alleles were associated with an increased risk of relapse. An implication of the IL-6 promoter -174 G/C polymorphism and the GG241 ICAM-1 genotype was also reported. With regard to serological biomarkers, elevated levels of angiopoietin-2 were associated with an unfavorable course of PMR. Methotrexate and anti-IL6 receptor antibody tocilizumab may be required in PMR patients with multiple relapses.
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- 2021
26. Disease activity influences the reclassification of rheumatoid arthritis into very high cardiovascular risk
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N. Vegas-Revenga, Ricardo Blanco, Belén Atienza-Mateo, Juan Carlos Quevedo-Abeledo, Miguel A. González-Gay, Alfonso Corrales, Iván Ferraz-Amaro, Virginia Portilla, and Universidad de Cantabria
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medicine.medical_specialty ,Diseases of the musculoskeletal system ,Disease ,030204 cardiovascular system & hematology ,Carotid Intima-Media Thickness ,Risk Assessment ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Diabetes mellitus ,Internal medicine ,Humans ,Medicine ,Rheumatoid arthritis ,030203 arthritis & rheumatology ,business.industry ,Middle Aged ,medicine.disease ,Cardiovascular disease ,Comorbidity ,Carotid plaque ,Rheumatology ,Carotid Arteries ,RC925-935 ,Cardiovascular Diseases ,Heart Disease Risk Factors ,Orthopedic surgery ,business ,Dyslipidemia ,Research Article ,Kidney disease - Abstract
Background: Previous studies have shown that risk chart algorithms, such as the Systematic Coronary Risk Assessment (SCORE), often underestimate the actual cardiovascular (CV) risk of patients with rheumatoid arthritis (RA). In contrast, carotid ultrasound was found to be useful to identify RA patients at high CV. In the present study, we aimed to determine if specific disease features influence the CV risk reclassification of RA patients assessed by SCORE risk charts and carotid ultrasound. Methods: 1279 RA patients without previous CV events, diabetes, or chronic kidney disease were studied. Disease characteristics including disease activity scores, CV comorbidity, SCORE calculation, and the presence of carotid plaque by carotid ultrasound were assessed. A multivariable regression analysis was performed to evaluate if the reclassification into very high CV risk category was independently associated with specific features of the disease including disease activity. Additionally, a prediction model for reclassification was constructed in RA patients. Results: After carotid ultrasound assessments, 54% of the patients had carotid plaque and consequently fulfilled definition for very high CV risk. Disease activity was statistically significantly associated with reclassification after fully multivariable analysis. A predictive model containing the presence of dyslipidemia and hypertension, an age exceeding 54 years, and a DAS28-ESR score equal or higher than 2.6 yielded the highest discrimination for reclassification. Conclusion: Reclassification into very high CV risk after carotid ultrasound assessment occurs in more than the half of patients with RA. This reclassification can be independently explained by the activity of the disease. Funding: This work was supported by a grant to I.F-A. from the Spanish Ministry of Health, Subdirección General de Evaluación y Fomento de la Investigación, Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016, and by Fondo Europeo de Desarrollo Regional — FEDER (Fondo de Investigaciones Sanitarias, FIS PI14/00394, PI17/00083). Prof. González-Gay’s research is supported by the Instituto de Salud Carlos III (ISCIII) (Fondo de Investigación Sanitaria grants PI06/0024, PI09/00748, PI12/00060, PI15/00525, PI18/00043) and the ISCIII RETICS programs (RD12/0009 and RD16/0012).
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- 2021
27. Upadacitinib monotherapy versus methotrexate monotherapy in methotrexate-naïve Japanese patients with rheumatoid arthritis: a sub-analysis of the Phase 3 SELECT-EARLY study
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Ronald F van Vollenhoven, Tatsuya Atsumi, Alan Friedman, Tsutomu Takeuchi, Aileen L. Pangan, Vibeke Strand, Yukitaka Ueki, Maureen Rischmueller, Su Chen, Ricardo Blanco, Ricardo Machado Xavier, Clinical Immunology and Rheumatology, AII - Inflammatory diseases, and AMS - Musculoskeletal Health
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musculoskeletal diseases ,rheumatoid arthritis ,Adult ,Male ,medicine.medical_specialty ,Artrite reumatóide ,Gastroenterology ,Metotrexato ,Arthritis, Rheumatoid ,Japão ,Rheumatology ,Double-Blind Method ,Japan ,Internal medicine ,medicine ,Humans ,heterocyclic compounds ,Rheumatoid arthritis ,skin and connective tissue diseases ,business.industry ,Middle Aged ,medicine.disease ,upadacitinib ,DMARD ,Methotrexate ,Treatment Outcome ,Upadacitinib ,Antirheumatic Agents ,Female ,business ,Heterocyclic Compounds, 3-Ring ,medicine.drug ,Tratamento farmacológico - Abstract
Objective: To assess upadacitinib monotherapy versus methotrexate (MTX) in MTX-naïve Japanese patients with rheumatoid arthritis (RA) from the Phase 3 SELECT-EARLY study. Methods: Japanese patients were randomized 2:1:1:1 to upadacitinib 7.5, 15, or 30 mg daily or MTX 7.5 mg/week (titrated to ≤15 mg/week). Efficacy endpoints included the proportion of patients reporting 20% improvement in American College of Rheumatology criteria (ACR20) at week 12 and change from baseline in modified Total Sharp Score (mTSS) at week 24. Other efficacy outcomes were also assessed at weeks 12 and/or 24. Safety was assessed over 24 weeks. Results: Of 138 Japanese patients enrolled, significantly more patients treated with upadacitinib 7.5 and 15 mg, but not 30 mg, reported ACR20 responses versus MTX at week 12. Significantly smaller changes from baseline in mTSS were observed with upadacitinib 15 and 30 mg, but not 7.5 mg, versus MTX at week 24. Upadacitinib demonstrated an acceptable safety profile; herpes zoster occurred in 3.6%, 7.4%, and 7.1% of patients treated with upadacitinib 7.5, 15, and 30 mg, respectively. Conclusion: Similar to the global study population, upadacitinib demonstrated clinical efficacy superior to placebo in the Japanese subpopulation. Among upadacitinib-treated patients, herpes zoster was least common with 7.5 mg.
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- 2021
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28. Potential relation of cardiovascular risk factors to disease activity in patients with axial spondyloarthritis
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Carlos Fernández Díaz, Esther F. Vicente, Javier Rueda-Gotor, María Luz García Vivar, Juan Carlos Quevedo-Abeledo, Esther Montes Perez, Carlos Rodríguez-Lozano, Ricardo Blanco, Rafaela Ortega-Castro, María Lourdes Ladehesa-Pineda, Santos Castañeda, Rosa Expósito, Cristina Fernández-Carballido, Joaquín Anino-Fernández, Alfonso Corrales, M Paz Martínez-Vidal, Eva Galíndez-Agirregoikoa, Iñigo González Mazón, Chamaida Plasencia-Rodríguez, Diana Peiteado, Fernanda Genre, Javier Llorca, Miguel A. González-Gay, David Castro-Corredor, Virginia Portilla, Iván Ferraz-Amaro, and Universidad de Cantabria
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cardiovascular risk factors ,medicine.medical_specialty ,Cardiovascular risk factors ,Diseases of the musculoskeletal system ,Disease activity ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Internal medicine ,medicine ,Orthopedics and Sports Medicine ,In patient ,030212 general & internal medicine ,Axial spondyloarthritis ,Original Research ,030203 arthritis & rheumatology ,business.industry ,Extra-Articular Manifestations and Comorbidities in Spondyloarthritis ,axial spondyloarthritis ,Increased risk ,RC925-935 ,business ,disease activity - Abstract
Background: Axial spondyloarthritis (axSpA) patients are known to have a higher prevalence of several comorbidities, including, among others, an increased risk of atherosclerosis, hypertension, dyslipidemia, and diabetes. The purpose of the present study was to determine whether the sum of traditional cardiovascular (CV) risk factors is related to disease characteristics, such as disease activity, in patients with axSpA. Methods: A cross-sectional study that encompassed 804 patients with axSpA was conducted. Patients were assessed for the presence of five traditional CV risk factors (diabetes mellitus, dyslipidemia, hypertension, obesity, and smoking status), and disease activity measurements. A multivariable regression analysis was performed to evaluate whether the number of classic CV risk factors was independently associated with specific features of the disease, to include disease activity. Results: A multivariable analysis showed that Ankylosing Spondylitis Disease Activity Score-C reactive protein (ASDAS-CRP) activity score was significantly higher in patients with 1 [beta coefficient 0.3 (95% confidence interval (CI) 0.1-0.5), p = 0.001] and ?2 [beta coefficient 0.5 (95% CI 0.3-0.7), p = 0.000] CV risk factors compared with those without CV risk factors. Similarly, patients with 1 [OR 2.00 (95%CI 0.99-4.02), p = 0.053] and ?2 [OR 3.39 (95%CI 1.82-6.31), p = 0.000] CV risk factors had a higher odds ratio for the presence of high disease activity compared with the zero CV category. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) activity score was significantly associated with the number of CV risk factors, being higher in patients with more CV risk factors. These relationships showed a CV risk factor-dependent effect being beta coefficients and ORs higher for the effect of ?2 over 1 CV risk factor. Conclusion: Among patients with axSpA, as the number of traditional CV risk factors increased, disease activity similarly increases in an independent manner. Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/ or publication of this article: This research was funded by a grant to MAG-G from the Instituto de Salud Carlos III (ISCIII) (Fondo de Investigación Sanitaria grants PI06/0024, PI09/00748, PI12/00060, PI15/00525, PI18/00043) and the ISCIII RETICS programs (RD12/0009 and RD16/0012).
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- 2021
29. Endothelial Progenitor Cells: Relevant Players in the Vasculopathy and Lung Fibrosis Associated with the Presence of Interstitial Lung Disease in Systemic Sclerosis Patients
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David Iturbe-Fernández, Raquel López-Mejías, Belén Atienza-Mateo, Ricardo Blanco, Sara Remuzgo-Martínez, Virginia Portilla, Víctor M. Mora-Cuesta, Verónica Pulito-Cueto, Oreste Gualillo, Miguel A. González-Gay, Raquel Pérez-Fernández, José M. Cifrián, Fernanda Genre, Alfonso Corrales, Leticia Lera-Gómez, Diana Prieto-Peña, and Universidad de Cantabria
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0301 basic medicine ,medicine.medical_specialty ,QH301-705.5 ,systemic sclerosis ,CD34 ,Medicine (miscellaneous) ,Interstitial lung disease ,Gastroenterology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Flow cytometry ,03 medical and health sciences ,Idiopathic pulmonary fibrosis ,0302 clinical medicine ,Internal medicine ,medicine ,Progenitor cell ,Biology (General) ,skin and connective tissue diseases ,Endothelial progenitor cells ,endothelial progenitor cells ,030203 arthritis & rheumatology ,interstitial lung disease ,medicine.diagnostic_test ,integumentary system ,business.industry ,Lung fibrosis ,Biomarker ,respiratory system ,medicine.disease ,respiratory tract diseases ,030104 developmental biology ,Rheumatoid arthritis ,embryonic structures ,cardiovascular system ,Biomarker (medicine) ,biomarker ,Systemic sclerosis ,business - Abstract
Endothelial progenitor cells (EPC), which are key effectors in the physiologic vascular network, have been described as relevant players in autoimmune diseases. We previously showed that EPC frequency may help to identify the presence of interstitial lung disease (ILD) in rheumatoid arthritis patients. Given that ILD constitutes the main cause of mortality in systemic sclerosis (SSc) patients, we aimed to determine the EPC contribution to the pathogenic processes of vasculopathy and lung fibrosis in SSc-ILD+. EPC quantification was performed by flow cytometry on blood from 83 individuals: 21 SSc-ILD+ patients and subjects from comparative groups (20 SSc-ILD− and 21 idiopathic pulmonary fibrosis (IPF) patients and 21 healthy controls (HC)). EPC were considered as CD34+, CD45low, CD309+, and CD133+. A significant increase in EPC frequency was found in SSc-ILD+ patients when compared to HC (p <, 0.001). SSc-ILD+ patients exhibited a higher EPC frequency than SSc-ILD− patients (p = 0.012), whereas it was markedly reduced compared to IPF patients (p <, 0.001). EPC frequency was higher in males (p = 0.04) and negatively correlated to SSc duration (p = 0.04) in SSc-ILD+ patients. Our results indicate a role of EPC in the processes of vasculopathy and lung fibrosis in SSc-ILD+. EPC frequency may be considered as a biomarker of ILD in SSc patients.
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- 2021
30. The Performance of Vascular Age in the Assessment of Cardiovascular Risk of Patients with Rheumatoid Arthritis
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Alfonso Corrales, Diana Prieto-Peña, Belén Atienza-Mateo, Juan Carlos Quevedo-Abeledo, Miguel A. González-Gay, Ricardo Blanco, Javier Llorca, Iván Ferraz-Amaro, and Universidad de Cantabria
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rheumatoid arthritis ,medicine.medical_specialty ,carotid plaque ,Population ,Vascular age ,030204 cardiovascular system & hematology ,Article ,03 medical and health sciences ,0302 clinical medicine ,vascular age ,Internal medicine ,medicine ,In patient ,Rheumatoid arthritis ,education ,Subclinical infection ,030203 arthritis & rheumatology ,education.field_of_study ,business.industry ,cardiovascular risk assessment ,Ultrasound ,Area under the curve ,Cardiovascular risk assessment ,General Medicine ,medicine.disease ,Carotid plaque ,Intima-media thickness ,Subclinical atherosclerosis ,Cardiology ,cardiovascular system ,business - Abstract
Background. Cardiovascular (CV) disease risk prediction models developed for use in the general population have suboptimal performance in patients with rheumatoid arthritis (RA). Vascular age (VA) is a new concept that has been proposed as a measure of CV &lsquo, relative&rsquo, risk instead of the &lsquo, absolute&rsquo, risk that current prediction models provide. In the present study we aim to study the performance of vascular age (VA) in the assessment of CV risk in patients with RA. We additionally aimed to analyze its relation with subclinical atherosclerosis as measured through carotid plaque ultrasound. Methods. A total of 1173 non-diabetic RA patients without previous CV events were included. Disease characteristics, SCORE, VA determined on SCORE and on carotid intima media thickness (cIMT), and the presence of plaque through carotid ultrasound were assessed. The interrelations of VA with SCORE, and its associations with subclinical carotid atherosclerosis were studied. Results. On average, RA patients had both a SCORE determined VA (4.7 years) and a cIMT-based VA (2.4 years) significantly higher than the chronological age. When these differences were analyzed in different age intervals, while VA based on SCORE was significantly higher compared to chronological age in all age ranges, VA determined on cIMT was significantly elevated only in RA patients younger than 60 years. The area under the curve analysis for the association of SCORE and VA with the presence of carotid plaque disclosed no differences between both parameters. VA was associated with the presence of carotid plaque after multivariable regression analysis in patients younger than 60 years old. Conclusion. VA is significantly higher than chronological age in patients with RA. The performance of VA in its relation to carotid plaque is similar to that of the SCORE.
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- 2020
31. Tocilizumab in refractory giant cell arteritis. Monotherapy versus combined therapy with conventional immunosuppressive drugs. Observational multicenter study of 134 patients
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Noelia Alvarez-Rivas, Francisca Sivera, Susana Romero-Yuste, Carles Galisteo, Santos Castañeda, Monica Calderón-Goercke, Elena Becerra-Fernández, Ignacio Villa, José L. Hernández, Vicente Aldasoro, Diana Prieto-Peña, Eugenio de Miguel, Rafael Melero, Miguel A. González-Gay, Ricardo Blanco, Eva Perez-Pampin, Catalina Gomez-Arango, Javier Narváez, Marcelino Revenga, and Clara Moriano
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medicine.medical_specialty ,Giant Cell Arteritis ,Azathioprine ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Tocilizumab ,Rheumatology ,Refractory ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Adverse effect ,Leflunomide ,030203 arthritis & rheumatology ,business.industry ,medicine.disease ,Giant cell arteritis ,Anesthesiology and Pain Medicine ,Treatment Outcome ,chemistry ,Pharmaceutical Preparations ,Methotrexate ,Vasculitis ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Objective To compare the efficacy and safety of TCZ in monotherapy (TCZMONO) vs. combined with conventional immunosuppressive drugs (TCZCOMBO) in Giant Cell Arteritis (GCA) in a clinical practice scenario. Methods Multicenter study of 134 patients with refractory GCA. Patients on TCZMONO (n = 82) were compared with those on TCZCOMBO (n = 52). Drugs were methotrexate (MTX) (n = 48), azathioprine (n = 3), and leflunomide (n = 1). The main outcomes were: prolonged remission (normalization of clinical and laboratory parameters for at least 6 months) and the number of relapses. Results Patients on TCZCOMBO were younger (68.8 ± 8.0 vs 71.2 ± 9.0 years; p = 0.04), with a trend to a longer GCA duration (median [IQR],18.5 [6.25–34.0] vs. 13.0 [7.75–33.5] months; p = 0.333), higher C-reactive protein (CRP) levels (2.1[1–4.7] vs 1.2 [0.2–2.4] mg/dL; p = 0.003), and more prevalence of extra-cranial large-vessel vasculitis (LVV) (57% vs. 34.1%; p = 0.007). In both groups, rapid and sustained improvement was observed. Despite the longer GCA duration, and the higher CRP levels and prevalence of LVV in the TCZCOMBO, the improvement was similar in both groups at 12 months. Moreover, in the TCZCOMBO group, prolonged remission was significantly higher at 12-month. Relapses and serious adverse events were similar in both groups. Conclusion In clinical practice, TCZ in monotherapy or combined with conventional immunosuppressive agents is effective and safe in patients with GCA. Nevertheless, the addition of immunosuppressive drugs, usually MTX, seems to allow a higher rate of prolonged remission, even in patients with a longer GCA duration, more extra-cranial LVV involvement, and higher acute-phase reactants.
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- 2020
32. AB0522 SAFETY PROFILE OF UPADACITINIB UP TO 3 YEARS IN PATIENTS WITH PSORIATIC ARTHRITIS: AN INTEGRATED ANALYSIS FROM THE PHASE 3 PROGRAM
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A. Rubbert-Roth, Philippe Goupille, B.J. Pierre-Louis, E. Lesser, Ricardo Blanco, Kevin L. Winthrop, V. F. Azevedo, R. Lippe, Carlo Salvarani, J. Liu, P. Nash, A. Lertratanakul, G.-R. Burmester, R. Mccaskill, Eric Ruderman, and S. Walko
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medicine.medical_specialty ,education.field_of_study ,Study drug ,business.industry ,Immunology ,Population ,Study Sponsor ,Serious infection ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Safety profile ,Psoriatic arthritis ,Rheumatology ,Internal medicine ,medicine ,Adalimumab ,Immunology and Allergy ,In patient ,education ,business ,medicine.drug - Abstract
Background:The efficacy and safety of upadacitinib (UPA), an oral Janus kinase inhibitor, in patients (pts) with active psoriatic arthritis (PsA) were demonstrated through 24 weeks in the phase 3 SELECT-PsA 1 and SELECT-PsA 2 placebo-controlled clinical trials.1,2Objectives:To describe the long-term integrated safety profile of UPA relative to adalimumab (ADA) in pts with PsA treated in the SELECT program.Methods:The SELECT-PsA program enrolled pts with prior inadequate response or intolerance to ≥1 non-biologic DMARD (SELECT-PsA 1) or ≥1 biologic DMARD (SELECT-PsA 2). Both trials include UPA 15 mg and 30 mg, and only SELECT-PsA 1 includes long-term comparison with ADA 40 mg every other week. Treatment-emergent adverse events (TEAEs: AE onset ≥first dose and ≤30 days after last dose for UPA and ≤70 days for ADA) were summarized for the following: pooled UPA 15; pooled UPA 30; and ADA. TEAEs are reported as exposure-adjusted event rates (EAERs; events/100 pts years [E/100 PY]) up to a cut-off date of 20 June 2020.Results:2257 pts received ≥1 dose of UPA 15 (N=907; 1247.2 PYs), UPA 30 (N=921; 1257.4 PYs), or ADA (N=429; 549.7 PYs), with median (max) exposures of 69 (155), 69 (154), and 68 (152) weeks, respectively. EAERs of TEAEs and serious AEs were generally similar between UPA 15 and ADA and higher with UPA 30; rates of AEs leading to study drug discontinuation were generally similar across all groups (Table 1). Similarly, rates of serious infection were comparable between UPA 15 and ADA and higher with UPA 30 (Figure 1 next page). The most common serious infection was pneumonia. Rates of herpes zoster were lower with UPA 15 than UPA 30 but higher than ADA. Most herpes zoster events involved a single dermatome; no events involved the central nervous system or other internal organs. Lower rates of opportunistic infections (OI) excluding tuberculosis were observed with UPA 15 vs UPA 30; the most common OI was mucosal candida infection. Malignancies were reported at similar rates across all treatment groups; no events of lymphoma were reported. Age-gender-adjusted standardized incidence ratios for malignancies excluding NMSC indicated no increased risk with UPA compared to the general population. Rates of adjudicated major adverse cardiovascular events and venous thromboembolic events were ≤0.3 E/100 PY for both UPA arms; all pts had ≥1 risk factor. One adjudicated gastrointestinal perforation was reported with UPA 15.Table 1.Overall Treatment-emergent AEs for Upadacitinib and Adalimumab (E/100 PY [95% CI])UPA 15 mg QDN=907(1247.2 PY)UPA 30 mg QDN=921(1257.4 PY)ADA 40 mg EOWN=429(549.7 PY)AEs263.9 (254.9, 272.9)321.5 (311.6, 331.5)286.5 (272.4, 300.7)Serious AEs10.3 (8.6, 12.1)13.2 (11.2, 15.2)9.6 (7.0, 12.2)AE leading to discontinuation6.7 (5.2, 8.1)7.8 (6.2, 9.3)7.8 (5.5, 10.2)Deathsa0.2 (-0.1, 0.4)0.2 (-0.0, 0.5)0.2 (-0.2, 0.5)aDeaths included non-treatment emergent deaths: UPA 15, 1; UPA 30, 1.ADA, adalimumab; AE, adverse event; CI, confidence interval; E, event; EOW, every other week; PY, patient years; QD, once daily; UPA, upadacitinib.Hepatic disorders were mostly transient, non-serious transaminase increases. Creatine phosphokinase elevations were reported more frequently with UPA 30 vs UPA 15; most were asymptomatic with no rhabdomyolysis reported. AEs of anemia, neutropenia, and lymphopenia were generally mild or moderate, non-serious. Except for rates of lymphopenia (higher with UPA 15), hepatic disorders, and neutropenia (both higher with ADA), lab-related TEAEs occurred at generally consistent rates between UPA 15 and ADA. Study drug discontinuation due to lab-related TEAEs was uncommon.Conclusion:The safety profiles of UPA 15 and ADA were generally similar; the rates of most AEs were higher with UPA 30 compared with ADA. Through the cut-off date, the safety profile of UPA 15 and UPA 30 in PsA pts demonstrated consistent results compared to what has been observed with UPA in rheumatoid arthritis.3References:[1]McInnes IB et al. Ann Rheum Dis, 2020; 79:12.[2]Mease PJ et al. Ann Rheum Dis, 2020.[3]Cohen SB et al. Ann Rheum Dis, 2020.Figure 1Acknowledgements:AbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial. AbbVie, Inc was the study sponsor, contributed to study design, data collection, analysis & interpretation, and to writing, reviewing, and approval of final version. No honoraria or payments were made for authorship. Medical writing support was provided by Ramona Vladea, PhD of AbbVie Inc.Disclosure of Interests:Gerd Rüdiger Burmester Speakers bureau: AbbVie, Gilead, Lilly, Pfizer, Consultant of: AbbVie, Gilead, Lilly, Pfizer, Kevin Winthrop Consultant of: UCB Pharma, Pfizer, Bristol-Myers Squibb, Eli Lilly, AbbVie, Gilead, Galapagos, and Roche, Grant/research support from: UCB Pharma, Pfizer, Bristol-Myers Squibb, Eli Lilly, AbbVie, Gilead, Galapagos, and Roche, Ricardo Blanco Consultant of: Abbvie, Lilly, Novartis, Pfizer, Roche, Bristol-Myers, Janssen, and MSD, Grant/research support from: Abbvie, MSD and Roche, Peter Nash Consultant of: AbbVie, BMS, Roche, Pfizer, Janssen, Amgen, Sanofi-Aventis, UCB, Eli Lilly, Novartis, and Celgene, Grant/research support from: AbbVie, BMS, Roche, Pfizer, Janssen, Amgen, Sanofi-Aventis, UCB, Eli Lilly, Novartis, and Celgene, Philippe Goupille Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Grant/research support from: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Valderilio F Azevedo Consultant of: AbbVie, BMS, Pfizer, Janssen, Amgen, Novartis, Eli Lilly, UCB, Celltrion and GSK, Grant/research support from: AbbVie, BMS, Pfizer, Janssen, Amgen, Novartis, Eli Lilly, UCB, Celltrion and GSK, Carlo Salvarani Consultant of: Roche, Sanofi-Genzyme, AbbVie, Pfizer, Lilly, Novartis, Amgen, Grant/research support from: Roche, Sanofi-Genzyme, AbbVie, Pfizer, Lilly, Novartis, Amgen, Andrea Rubbert-Roth Consultant of: AbbVie, BMS, Chugai, Roche, Gilead, Janssen, Lilly, Sanofi, Amgen, Novartis, Grant/research support from: AbbVie, BMS, Chugai, Roche, Gilead, Janssen, Lilly, Sanofi, Amgen, Novartis, Elizabeth Lesser Shareholder of: AbbVie, Employee of: AbbVie, Reva McCaskill Shareholder of: AbbVie, Employee of: AbbVie, Jianzhong Liu Shareholder of: AbbVie, Employee of: AbbVie, Bosny Pierre-Louis Shareholder of: AbbVie, Employee of: AbbVie, Sandra Walko Shareholder of: AbbVie, Employee of: AbbVie, Ralph Lippe Shareholder of: AbbVie, Employee of: AbbVie, Apinya Lertratanakul Shareholder of: AbbVie, Employee of: AbbVie, Eric Ruderman Consultant of: AbbVie, Amgen, Gilead, Janssen, Lilly, Novartis, and Pfizer.
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- 2021
33. Response to: ‘Correspondence to ‘Prevalence of hospital PCR-confirmed COVID-19 cases in patients with chronic inflammatory and autoimmune rheumatic diseases’’ by Wuet al
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María José Galindo, José María Álvaro-Gracia, José L. Pablos, and Ricardo Blanco
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0301 basic medicine ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Immunology ,Arthritis ,Economic shortage ,Polymerase Chain Reaction ,Medical care ,General Biochemistry, Genetics and Molecular Biology ,Autoimmune Diseases ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Pcr test ,Rheumatic Diseases ,Internal medicine ,Epidemiology ,Pandemic ,Prevalence ,medicine ,Humans ,Immunology and Allergy ,In patient ,030203 arthritis & rheumatology ,business.industry ,COVID-19 ,medicine.disease ,Hospitals ,030104 developmental biology ,business - Abstract
We thank Wu et al for their interest in our study reporting on the prevalence of COVID-19 in patients with rheumatic diseases (RMD).1 Wu et al suggest that potential detection bias due to more frequent regular visits to hospitals in patients with RMD may explain the observed greater prevalence of hospital COVID-19 cases in these patients. However, this is highly unlikely since the identification of hospital PCR+ cases was performed in April 2020, still in the peak phase of COVID-19 pandemic in Spain, when the regular scheduled follow-up visits had been cancelled and restricted to urgent medical care. In addition, PCR test shortage resulted in the need to restrict testing to ‘COVID-19-likely’ symptomatic patients at emergency departments, making unlikely preferential testing of RMD or other specific patients. Nevertheless, we cannot exclude other biases such as greater …
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- 2020
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34. Anti-IL-6 Receptor Tocilizumab in Refractory Graves’ Orbitopathy: National Multicenter Observational Study of 48 Patients
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Marcelino Revenga, Valvanera Pinillos, Ángel García-Aparicio, Margarita Sánchez-Orgaz, Vanesa Calvo-Río, L. Sanchez-Bilbao, Belén Atienza-Mateo, Santos Castañeda, Ricardo Blanco, Elia Valls-Pascual, Beatriz Valls-Espinosa, Ana Blanco, Ángel Mora, José L. Hernández, Verónica Rodriguez-Mendez, Eva Tomero, D. Martínez-López, Diana Peiteado, Vega Jovaní, I. González-Mazón, O. Maiz-Alonso, M. Fernandez-Prada, Arantxa Conesa, Raúl Veroz-González, Juan A. Troyano, Miguel A. González-Gay, Elena Aurrecoechea, R. Demetrio-Pablo, I. Torre-Salaberri, Ángel López-Vázquez, Francisco J. Toyos-Sáenz de Miera, UAM. Departamento de Medicina, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-IP), and Universidad de Cantabria
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medicine.medical_specialty ,Intraocular pressure ,Visual acuity ,extrathyroidal manifestations ,Medicina ,Graves' disease ,lcsh:Medicine ,Gastroenterology ,Article ,Graves' ophthalmopathy ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Tocilizumab ,Refractory ,Internal medicine ,Graves’ ophthalmopathy ,medicine ,Adverse effect ,030203 arthritis & rheumatology ,disease ,Graves’ ,business.industry ,thyroid-associated ophthalmopathy ,lcsh:R ,General Medicine ,medicine.disease ,corticoid-resistant ,eye diseases ,ophthalmopathy ,Methylprednisolone ,chemistry ,030221 ophthalmology & optometry ,medicine.symptom ,business ,Graves’ disease ,medicine.drug - Abstract
Graves&rsquo, orbitopathy (GO) is the most common extrathyroidal manifestation of Graves&rsquo, disease (GD). Our aim was to assess the efficacy and safety of Tocilizumab (TCZ) in GO refractory to conventional therapy. This was an open-label multicenter study of glucocorticoid-resistant GO treated with TCZ. The main outcomes were the best-corrected visual acuity (BVCA), Clinical Activity Score (CAS) and intraocular pressure (IOP). These outcome variables were assessed at baseline, 1st, 3rd, 6th and 12th month after TCZ therapy onset. The severity of GO was assessed according to the European Group on Graves&rsquo, Orbitopathy (EUGOGO). We studied 48 (38 women and 10 men) patients (95 eyes), mean age ±, standard deviation 51 ±, 11.8 years. Before TCZ and besides oral glucocorticoids, they had received IV methylprednisolone (n = 43), or selenium (n = 11). GO disease was moderate (n =29) or severe (n = 19) and dysthyroid optic neuropathy (DON) (n = 7). TCZ was used in monotherapy (n = 45) or combined (n = 3) at a dose of 8 mg/kg IV every four weeks (n = 43) or 162 mg/s.c. every week (n = 5). TCZ yielded a significant improvement in all of the main outcomes at the 1st month that was maintained at one year. Comparing the baseline with data at 1 year all of the variables improved, BCVA (0.78 ±, 0.25 vs. 0.9 ±, 0.16, p = 0.0001), CAS (4.64 ±, 1.5 vs. 1.05 ±, 1.27, p = 0.0001) and intraocular pressure (IOP) (19.05 ±, 4.1 vs. 16.73 ±, 3.4 mmHg, p = 0.007). After a mean follow-up of 16.1 ±, 2.1 months, low disease activity (CAS &le, 3), was achieved in 88 eyes (92.6%) and TCZ was withdrawn in 29 cases due to low disease activity (n = 25) or inefficacy (n = 4). No serious adverse events were observed. In conclusion, TCZ is a useful and safe therapeutic option in refractory GO treatment.
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- 2020
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35. Atherogenic index of plasma is associated with the severity of Hidradenitis Suppurativa: a case-control study
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Marcos A. González-López, J. Gonzalo Ocejo-Vinyals, Ricardo Blanco, José L. Hernández, Cristina Baldeón, Ana Elisabet López-Sundh, and Universidad de Cantabria
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medicine.medical_specialty ,Waist ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Blood Pressure ,030209 endocrinology & metabolism ,Clinical nutrition ,030204 cardiovascular system & hematology ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Insulin resistance ,Risk Factors ,Internal medicine ,Humans ,Medicine ,Hidradenitis suppurativa ,lcsh:RC620-627 ,Triglycerides ,Apolipoproteins B ,medicine.diagnostic_test ,business.industry ,Research ,Biochemistry (medical) ,Case-control study ,Atherogenic index of plasma ,nutritional and metabolic diseases ,Atherosclerosis ,medicine.disease ,Lipids ,lcsh:Nutritional diseases. Deficiency diseases ,C-Reactive Protein ,Blood pressure ,Case-Control Studies ,lipids (amino acids, peptides, and proteins) ,Atherogenic indexes ,Insulin Resistance ,business ,Lipid profile ,Dyslipidemia - Abstract
Background Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with several comorbidities and vascular risk factors, such as dyslipidemia. The present study aimed to assess the possible associations between the lipid profile and atherogenic indexes and the severity of HS. Methods This case-control study enrolled 78 HS patients and 62 healthy controls. Classic lipid profile and lipoprotein ratios, including the atherogenic index of plasma (AIP), were evaluated. The severity of HS was measured by the HS Physician Global Assessment (PGA). Results HS-patients had lower serum total cholesterol and HDL-C levels and higher AIP than the control group. AIP was positively correlated to BMI, waist circumference, systolic and diastolic blood pressure, LDL-C, triglycerides, non-HDL-C, ApoB, HOMA, and hs-CRP and negatively to HDL-C and ApoA1. For the overall lipid profile, only AIP was related to a more severe HS (PGA ≥ 3) after controlling for age, sex, BMI, insulin resistance (IR), active smoking, and statin use (r = 0.268; p = 0.023). Multiple logistic regression adjusted for age, sex, BMI, IR, smoking status and statin use, showed that AIP ≥ 0.11 was significantly associated with the severity of HS (OR, 4.38; CI 95%, 1.09–17.50; p = 0.037). Conclusions In conclusion, these results showed that AIP is significantly and independently associated with HS severity.
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- 2020
36. The Number of Traditional Cardiovascular Risk Factors Is Independently Correlated with Disease Activity in Patients with Psoriatic Arthritis
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Ricardo Blanco, Alicia García-Dorta, Natalia Palmou-Fontana, Belén Atienza-Mateo, D. Martínez-López, Diana Prieto-Peña, Laura de Armas-Rillo, Susana Armesto, Miguel A. González-Gay, Iván Ferraz-Amaro, and Universidad de Cantabria
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Adult ,Male ,cardiovascular risk factors ,medicine.medical_specialty ,Time Factors ,Disease ,Article ,03 medical and health sciences ,Psoriatic arthritis ,0302 clinical medicine ,cardiovascular disease ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Disease activity ,Cardiovascular risk factors ,Aged ,030203 arthritis & rheumatology ,psoriatic arthritis ,lcsh:R5-920 ,medicine.diagnostic_test ,business.industry ,Arthritis, Psoriatic ,General Medicine ,Odds ratio ,Middle Aged ,medicine.disease ,Cardiovascular disease ,Atherosclerosis ,disease activity ,atherosclerosis ,Cross-Sectional Studies ,Heart Disease Risk Factors ,Female ,Metabolic syndrome ,Lipid profile ,business ,lcsh:Medicine (General) ,Dyslipidemia ,Kidney disease - Abstract
Background and objectives: Psoriatic arthritis (PsA) is associated with several comorbidities, including among others an increased risk of cardiovascular (CV) disease, atherosclerosis, metabolic syndrome, hypertension dyslipidemia, and diabetes. The purpose of the present study was to determine how the number of CV risk factors correlates with disease related data such as disease activity. Materials and Methods: Cross-sectional study that encompassed 305 patients who fulfilled the CASPAR criteria for PsA were assessed for lipid profile, disease activity measurements, and the presence of six traditional CV risk factors (diabetes mellitus, dyslipidemia, hypertension, obesity, chronic kidney disease, and smoking status). A multivariable regression analysis, adjusted for age, sex, and disease duration, was performed to evaluate if the number of classic CV risk factors was independently related with specific features of the disease, including disease activity. Results: Disease duration was found to be higher, after adjustment for age and sex, in patients with 1 or 2, and 3 or higher CV factors, compared to those patients without CV risk factors. Similarly, DAPSA (Disease Activity in PSoriatic Arthritis score) was found to be independently upregulated in patients with a higher number of CV risk factors. In this sense, as DAPSA score increases the odds ratio (OR) of having 1 or 2 (OR 1.12 (95% confidence interval (CI) 1.03&ndash, 1.21), p = 0.010), and 3 or higher (OR 1.15 (95% CI 1.04&ndash, 1.26), p = 0.004) CV factors was significantly higher compared to no CV risk factors category. This was independently found after adjustment for age, sex, and disease duration. Conclusions: PsA patients with a higher number of CV risk factors exhibit an upregulated disease activity compared to those without them. This is independent of disease duration and other demographics factors.
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- 2020
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37. Long-term Follow-up and Optimization of Infliximab in Refractory Uveitis Due to Behçet Disease: National Study of 103 White Patients
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José Luis, Martín-Varillas, Belén, Atienza-Mateo, Vanesa, Calvo-Rio, Emma, Beltrán, Juan, Sánchez-Bursón, Alfredo, Adán, Marisa, Hernández-Garfella, Elia, Valls-Pascual, Agustí, Sellas-Fernández, Norberto, Ortego, Olga, Maíz, Ignacio, Torre, Cruz, Fernández-Espartero, Vega, Jovani, Diana, Peiteado, David Díaz, Valle, Elena, Aurrecoechea, Miguel A, Caracuel, Alfredo J, García-González, Enrique Raya, Álvarez, Nuria, Vegas-Revenga, Rosalía, Demetrio-Pablo, Santos, Castañeda, Miguel A, González-Gay, José Luis, Hernández, Ricardo, Blanco, and Fred A, Pagés
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medicine.medical_specialty ,Tuberculosis ,Long term follow up ,Immunology ,Behçet disease ,short and long-term follow-up ,Uveitis ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Refractory ,Internal medicine ,medicine ,Immunology and Allergy ,Humans ,Adverse effect ,Retrospective Studies ,030203 arthritis & rheumatology ,business.industry ,Behcet disease ,Behcet Syndrome ,medicine.disease ,Infliximab ,Pneumonia ,Treatment Outcome ,030221 ophthalmology & optometry ,uveitis ,business ,infliximab ,optimization ,medicine.drug ,Follow-Up Studies - Abstract
ObjectiveIn a large series of White patients with refractory uveitis due to Behçet disease (BD) being treated with infliximab (IFX), we assessed (1) long-term efficacy and safety of IFX, and (2) IFX optimization when ocular remission was achieved.MethodsOur multicenter study of IFX-treated patients with BD uveitis refractory to conventional immunosuppressant agents treated 103 patients/185 affected eyes with IFX as first biologic therapy in the following intervals: 3–5 mg/kg intravenous at 0, 2, 6, and then every 4–8 weeks. The main outcome variables were analyzed at baseline, first week, first month, sixth month, first year, and second year of IFX therapy. After remission, based on a shared decision between patient and clinician, IFX optimization was performed. Efficacy, safety, and cost of IFX therapy were evaluated.ResultsIn the whole series (n = 103), main outcome variables showed a rapid and maintained improvement, reaching remission in 78 patients after a mean IFX duration of 31.5 months. Serious adverse events were observed in 9 patients: infusion reactions (n = 4), tuberculosis (n = 1),Mycobacterium aviumpneumonia (n = 1), severe oral ulcers (n = 1), palmoplantar psoriasis (n = 1), and colon carcinoma (n = 1). In the optimization subanalysis, the comparative study between optimized and nonoptimized groups showed (1) no differences in clinical characteristics at baseline, (2) similar maintained improvement in most ocular outcomes, (3) lower severe adverse events, and (4) lower mean IFX costs in the optimized group (€4826.52 vs €9854.13 per patient/yr).ConclusionIFX seems to be effective and relatively safe in White patients with refractory BD uveitis. IFX optimization is effective, safe, and cost-effective.
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- 2020
38. Clinical Outcomes of Patients with COVID-19 and Chronic Inflammatory and Autoimmune Rheumatic Diseases: A Multicentric Matched-Cohort Study
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Natalia Mena-Vázquez, Miguel A. González-Gay, José L. Pablos, Ana Lledó, José María Álvaro-Gracia, Loreto Carmona, Miriam Retuerto, D. Martínez-López, Antonio Fernández-Nebro, Sara Manrique-Arija, David Fernández-Fernández, Isabel Castrejón, María José Galindo, Antonio Mera-Varela, and Ricardo Blanco
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medicine.medical_specialty ,Prognostic variable ,business.industry ,Inflammatory arthritis ,medicine.disease ,Logistic regression ,Comorbidity ,Obesity ,Internal medicine ,Diabetes mellitus ,Cohort ,medicine ,business ,Cohort study - Abstract
BackgroundThe impact of inflammatory rheumatic diseases on COVID-19 severity is poorly known. Here we compare the outcomes of a cohort of rheumatic patients with a matched control cohort to identify potential risk factors for severe illness.MethodsIn this comparative cohort study, we identified hospital PCR+ COVID-19 rheumatic patients with chronic inflammatory arthritis (IA) or autoimmune/immunomediated diseases (AI/IMID). Non-rheumatic controls were randomly sampled 1:1, and matched by age, sex, and PCR date. The main outcome was severe COVID-19, defined as death, invasive ventilation, ICU admission, or serious complications. We assessed the association between the outcome and potential prognostic variables, adjusted by COVID treatment, using logistic regression.ResultsThe cohorts were composed of 456 rheumatic and non-rheumatic patients, in equal numbers. Mean age was 63 [IQR 53-78] and male sex 41% in both cohorts. Rheumatic diseases were IA (60%) and AI/IMID (40%). Most patients (74%) had been hospitalised, and the risk of severe COVID was 31.6% in the rheumatic and 28.1% in the non-rheumatic cohort. Ageing, male sex and previous comorbidity (obesity, diabetes, hypertension, cardiovascular, or lung disease) increased the risk in the rheumatic cohort by bivariate analysis. In logistic regression analysis, independent factors associated with severe COVID were increased age (OR 5.31; CI 3.14-8.95), male sex (2.13; CI 1.35-3.36) and having an AI/IMID (OR 1.98; CI 1.15-3.41).ConclusionIn patients with chronic inflammatory rheumatic diseases aging, sex and having an AI/IMID but not IA nor previous immunosuppressive therapies were associated with severe COVID-19.
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- 2020
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39. O31 Integrative analysis reveals a molecular stratification of systemic autoimmune diseases
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Carlo Chizzolini, Yolanda Jiménez Gómez, Pier Luigi Meroni, M.C. Castro-Villegas, Ralf Lesche, Fernanda Genre, Javier Martín, Raquel Faria, Márta Bocskai, Tommaso Schioppo, Emanuele de Rinaldis, Divi Cornec, Torsten Witte, Pierre-Emmanuel Jouve, Sikander Hayat, Johan Frostegård, Guillermo Barturen, Christophe Jamin, Laleh Khodadadi, Alfonso Corrales Martínez, Quentin Simon, Mariana Brandão, Chris Chamberlain, Alain Saraux, Javier Rodríguez-Ubreva, Francesc Català-Moll, Michaela Lehner, Ricard Cervera, Tania F. Rowley, Tianlu Li, Attila Balog, Enrique de Ramón, Maria Angeles Aguirre-Zamorano, Elena Carnero-Montoro, Rafaela Ortega-Castro, László Kovács, Velia Gerl, Carolina Artusi, Nancy Azevedo, Martin Kerick, Antonio López-Berrio, Esmeralda Neves, Anne-Lise Maudoux, Bénédicte Rouvière, Bernard Lauwerys, Maria Gerosa, Yiannis Ioannou, Fátima Farinha, Ian White, Tania Anjos, Sepideh Babaei, N.T. Baerlecken, Katja Kniesch, Jonathan Cremer, Joerg Mueller, Julie Ducreux, Lucas Le Lann, Norberto Ortego, Jerome Wojcik, Marialbert Acosta-Herrera, Maria Hernandez-Fuentes, Héctor Navarro-Linares, Maria Orietta Borghi, Inmaculada Jiménez Moleón, António Marinho, Rocío Aguilar-Quesada, Enrique Raya, Falk Hiepe, Raquel López Mejías, Mcdonald Fiona Mcdougall, Robert J. Benschop, Georg Stummvoll, Isabel Díaz Quintero, Esteban Ballestar, Aleksandra Maria Dufour, Jordi Martorell-Marugán, Elena Trombetta, Manuel Rodriguez Maresca, Miguel A. González-Gay, Valérie Devauchelle-Pensec, Maria Juarez, Carlos Vasconcelos, Doreen Belz, Yves Renaudineau, Donatienne Wynar, Jacqueline Marovac, Aurélie De Groof, Sandrine Jousse-Joulin, Alejandro Escudero-Contreras, Laurence Laigle, Ignasi Rodríguez-Pintó, Zuzanna Makowska, Isabel Almeida, Lorenzo Beretta, Damiana Álvarez-Errico, Nieves Varela, Montserrat Alvarez, Concepción Marañón, Ricardo Blanco Alonso, Daniel Toro-Domínguez, Ana Campar, Manuel Martínez-Bueno, Barbara Vigone, Francisco Javier Garrancho, Rik Lories, Gabriella Kádár, Michael Zauner, Silvia Thiel, Pedro Carmona-Sáez, María Concepción Fernández Roldán, Magdolna Deák, Marta E. Alarcón-Riquelme, Rosario Lopez-Pedrera, Qingyu Cheng, Sonja Dulic, Sara Remuzgo, Ana Lisa Taylor Tavares, Gerard Espinosa, Gaia Montanelli, Nuria Barbarroja, Sambasiva P. Rao, Eduardo Collantes-Estevez, Anne Buttgereit, Begoña Ubilla Garcia, Ernst R. Dow, Jorge Kageyama, Antonio Garcia-Gomez, Jacques-Olivier Pers, Nicolas Hunzelmann, and Ellen De Langhe
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Oncology ,medicine.medical_specialty ,Disease clusters ,business.industry ,Disease progression ,INCEPTION COHORT ,Internal medicine ,T cell immunity ,medicine ,Effective treatment ,Christian ministry ,Medical diagnosis ,business ,Unsupervised clustering - Abstract
Background Clinical heterogeneity, a hallmark of systemic autoimmune diseases (SADs) impedes early diagnosis and effective treatment, issues that may be addressed if patients could be grouped into a molecular defined stratification. Methods With the aim of reclassifying SADs independently of the clinical diagnoses, unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data of 918 patients with 7 SADs and 263 healthy controls was undertaken. An inception cohort prospectively followed for 6 and 14 months was studied to validate the results in early cases and analyze if cluster assignment was modified with time. Results Four clusters were identified Three aberrant clusters were ‘acute phase inflammatory’, ‘T cell immunity’, and ‘interferon’, each including all diagnoses, were defined by genetic, clinical, serological and cellular features. A fourth cluster showed no specific molecular pattern, to which 74% of healthy controls clustered with patients. The inception cohort showed that most patients were either assigned always to the same cluster or moved from the healthy-like cluster to a single aberrant cluster resembling the relapsing-remitting dynamic of these diseases, showing that single aberrant molecular signatures characterize each individual patient. Conclusions Patients with SADs share molecular signatures and can be therefore stratified into three disease clusters differentiating each patient into a specific molecular disease pathway. Such assignment is stable with time. These results have important implications for understanding disease progression and therapy design marking a paradigm shift in our view of SADs. Acknowledgment This work has been supported through a grant from the Innovative Medicines Initiative Joint Undertaking No. 115565 and in-kind and in-cash contributions from the EFPIA partners. G.B. is supported by the Instituto de Salud Carlos III (ISCIII, Spanish Health Ministry), through the Sara Borrell subprogram (CD18/00153). The authors would like to particularly express their gratitude to the patients, nurses and many others who helped directly or indirectly in the consecution of this study.
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- 2020
40. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases
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Jacqueline Marovac, Sandrine Jousse-Joulin, Magdolna Deák, Marta E. Alarcón-Riquelme, Laurence Laigle, Tania F. Rowley, Rosario Lopez-Pedrera, Inmaculada Jiménez Moleón, Tianlu Li, Héctor Navarro-Linares, Maria Orietta Borghi, Concepción Marañón, Michael Zauner, Mariana Brandão, Elena Carnero-Montoro, Quentin Simon, Aleksandra Maria Dufour, Antonio López-Berrio, Isabel Díaz Quintero, Nancy Azevedo, Maria Juarez, Esmeralda Neves, Maria Angeles Aguirre-Zamorano, Qingyu Cheng, Ian White, Michaela Lehner, Ernst R. Dow, Manuel Martínez-Bueno, Pier Luigi Meroni, Falk Hiepe, Alejandro Escudero-Contreras, Barbara Vigone, Yolanda Jiménez Gómez, Rik Lories, Jacques-Olivier Pers, Ralf Lesche, Ana Campar, Ellen De Langhe, Bénédicte Rouvière, Rafaela Ortega-Castro, Raquel Faria, Nuria Barbarroja, Jorge Kageyama, Sambasiva P. Rao, Ignasi Rodríguez-Pintó, M.C. Castro-Villegas, Julie Ducreux, Lucas Le Lann, Raquel López Mejías, Tania Anjos, Gabriella Kádár, Robert J. Benschop, Sonja Dulic, Norberto Ortego, Enrique Raya, Laleh Khodadadi, Elena Trombetta, Francisco Javier Garrancho, Pierre-Emmanuel Jouve, Manuel Rodriguez Maresca, Javier Rodríguez-Ubreva, Antonio Garcia-Gomez, Nieves Varela, Sara Remuzgo, Christophe Jamin, Fátima Farinha, Alain Saraux, Johan Frostegård, Carlos Vasconcelos, Anne Buttgereit, Alfonso Corrales Martínez, Isabel Almeida, Carolina Artusi, Nicolas Hunzelmann, Begoña Ubilla Garcia, László Kovács, Velia Gerl, Enrique de Ramón, Emanuele de Rinaldis, Donatienne Wynar, N.T. Baerlecken, Katja Kniesch, Damiana Álvarez-Errico, Yiannis Ioannou, Jonathan Cremer, Jerome Wojcik, Esteban Ballestar, Silvia Thiel, Daniel Toro-Domínguez, Joerg Mueller, António Marinho, Zuzanna Makowska, Pedro Carmona-Sáez, Lorenzo Beretta, Ricardo Blanco Alonso, María Teruel, Bernard Lauwerys, Eduardo Collantes-Estevez, Anne-Lise Maudoux, Georg Stummvoll, Maria Gerosa, Miguel A. González-Gay, María Concepción Fernández Roldán, Doreen Belz, Sepideh Babaei, Chris Chamberlain, Yves Renaudineau, Maria Hernandez-Fuentes, Francesc Català-Moll, Rocío Aguilar-Quesada, Aurélie De Groof, Montserrat Alvarez, Sikander Hayat, Guillermo Barturen, Jordi Martorell-Marugán, Attila Balog, Valérie Devauchelle-Pensec, Martin Kerick, Marialbert Acosta-Herrera, Mcdonald Fiona Mcdougall, Divi Cornec, Torsten Witte, Ricard Cervera, Javier Martín, Carlo Chizzolini, Márta Bocskai, Tommaso Schioppo, Fernanda Genre, Gaia Montanelli, Ana Lisa Taylor Tavares, and Gerard Espinosa
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Oncology ,medicine.medical_specialty ,business.industry ,Molecular Disease ,INCEPTION COHORT ,Clinical trial ,Transcriptome ,Internal medicine ,Clinical heterogeneity ,Medicine ,Effective treatment ,Medical diagnosis ,business ,Unsupervised clustering - Abstract
SUMMARYBackgroundClinical heterogeneity, a hallmark of systemic autoimmune diseases (SADs) impedes early diagnosis and effective treatment, issues that may be addressed if patients could be grouped into a molecular defined stratification.MethodsWith the aim of reclassifying SADs independently of the clinical diagnoses, unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data of 918 patients with 7 SADs and 263 healthy controls was undertaken. In addition, an inception cohort was prospectively followed for 6 and 14 months to validate the results and analyze if cluster assignment changed or not with time.ResultsFour clusters were identified. Three clusters were aberrant, representing ‘inflammatory’, ‘lymphoid’, and ‘interferon’ patterns each including all diagnoses and defined by genetic, clinical, serological and cellular features. A fourth cluster showed no specific molecular pattern and accumulated also healthy controls. An independent inception cohort showed that with time, the molecular clusters remain stable, showing that single aberrant molecular signatures characterize each individual patient.ConclusionsPatients with SADs can be jointly stratified into three stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of therapy non-responsiveness marking a paradigm shift in the view of SADs.
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- 2020
41. Association of retinol binding protein4 (RBP4) and ghrelin plasma levels with insulin resistance and disease severity in non-diabetic patients with hidradenitis suppurativa
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Sandra Guiral, Ricardo Blanco, José L. Hernández, Virginia Portilla, Marcos A. González-López, J. Gonzalo Ocejo-Viñals, I. Vilanova, Cristina Mata, and Universidad de Cantabria
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0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Dermatology ,Biochemistry ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Retinol-binding protein 4 ,Internal medicine ,Diabetes mellitus ,Medicine ,Humans ,Hidradenitis suppurativa ,Molecular Biology ,Retinol binding protein 4 ,biology ,business.industry ,Middle Aged ,medicine.disease ,Ghrelin ,Hidradenitis Suppurativa ,030104 developmental biology ,Endocrinology ,Cross-Sectional Studies ,Case-Control Studies ,biology.protein ,Biomarker (medicine) ,Female ,Insulin Resistance ,business ,Retinol binding ,Body mass index ,Retinol-Binding Proteins, Plasma - Abstract
Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with insulin resistance (IR). Retinol binding protein 4 (RBP4) and ghrelin are two bioactive proteins that have been involved in glucose metabolism and IR, but also in the regulation of immune and inflammatory processes. The aim of this study was to determine the serum levels of RBP4 and ghrelin in patients with HS, and to assess the possible relationship between these levels and IR, disease severity and HS risk. A total of 137 subjects (77 HS patients and 60 controls) without diabetes mellitus were enrolled in this cross-sectional study. Patients with HS had significantly higher RBP4 but lower ghrelin plasma levels than controls, independently of body mass index (BMI). Serum RBP4 levels were positively correlated to disease severity and IR in HS patients. However, we found no association between ghrelin levels and any clinical or laboratory parameters. Moreover, high serum RBP4 and low ghrelin levels were associated with an increased risk for HS. Our results suggest that high RBP4 levels may be a surrogate biomarker for IR in patients with HS. Moreover, increased RBP4 and decreased ghrelin levels could also be independent risk factors for the development of HS.
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- 2020
42. Abatacept in interstitial lung disease associated with rheumatoid arthritis: national multicenter study of 263 patients
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Paloma Vela Casasempere, Santos Castañeda, Juan R D Jiménez de Aberásturi, A. Urruticoechea-Arana, Clara Aguilera-Cros, Francisco Ortiz-Sanjuán, Ruben López-Sánchez, Iñigo Hernández Rodríguez, Susana Romero-Yuste, Neus Quillis-Marti, Antonio Juan-Mas, J. M. Blanco-Madrigal, A. Ruibal-Escribano, José Antonio Bernal-Vidal, Julia Fernández-Melón, Jesús C Fernández-López, María C Fito, José L. Hernández, Raul Castellanos-Moreira, F Javier Narváez García, Natalia Mena-Vázquez, Carmen Carrasco-Cubero, Cilia Peralta-Ginés, José L. Andreu, Samantha Rodríguez-Muguruza, Evelin C Cervantes Pérez, Ivette Casafont-Solé, Pilar Morales-Garrido, María Gema Bonilla Hernán, Cristina Hidalgo-Calleja, Sebastián C Rodríguez-García, Iván Cabezas-Rodríguez, Sonia Castro-Oreiro, C. Ojeda-Garcia, Raquel Almodóvar-González, Manuel J Moreno-Ramos, C. Fernández-Díaz, Blanca Garcia-Magallon, A. García-Valle, Eva Salgado-Pérez, Rosa Expósito-Molinero, Carmen González-Montagut, Ana María López-Robles, O. Maiz-Alonso, Trinidad Pérez-Sandoval, Rafael Benito Melero-González, Lorena Pérez-Albadalejo, Natividad del Val del Amo, Javier Loricera-García, Miguel A. González-Gay, Ángel García-Aparicio, Luis Arboleya-Rodríguez, Ricardo Blanco, Iván Castellvi-Barranco, Erique Raya-Alvarez, Lorena Expósito-Pérez, Mireia López-Corbeto, Sergio Ordóñez-Palau, Isabel Serrano-García, Alejandro Olivé, Sabela Fernández-Aguado, Manuel Rodríguez-Gómez, Patricia Carreira-Delgado, Deseada Palma-Sánchez, María N Alvarez-Rivas, and Ignacio Villa
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Male ,rheumatoid arthritis ,musculoskeletal diseases ,Vital capacity ,medicine.medical_specialty ,High-resolution computed tomography ,abatacept ,interstitial lung disease ,high-resolution computed tomography ,Gastroenterology ,behavioral disciplines and activities ,Abatacept ,Arthritis, Rheumatoid ,FEV1/FVC ratio ,Rheumatology ,Usual interstitial pneumonia ,Interquartile range ,DLCO ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Lung volumes ,medicine.diagnostic_test ,business.industry ,Interstitial lung disease ,respiratory system ,medicine.disease ,abatacept, high-resolution computed tomography, interstitial lung disease, rheumatoid arthritis ,respiratory tract diseases ,body regions ,Treatment Outcome ,Antirheumatic Agents ,Female ,Lung Diseases, Interstitial ,Tomography, X-Ray Computed ,business - Abstract
Objective To assess the efficacy of abatacept (ABA) in RA patients with interstitial lung disease (ILD) (RA-ILD). Methods This was an observational, multicentre study of RA-ILD patients treated with at least one dose of ABA. ILD was diagnosed by high-resolution CT (HRCT). We analysed the following variables at baseline (ABA initiation), 12 months and at the end of the follow-up: Modified Medical Research Council (MMRC) scale (1-point change), forced vital capacity (FVC) or diffusion lung capacity for carbon monoxide (DLCO) (improvement or worsening ≥10%), HRCT, DAS on 28 joints evaluated using the ESR (DAS28ESR) and CS-sparing effect. Results We studied 263 RA-ILD patients [150 women/113 men; mean (s.d.) age 64.6 (10) years]. At baseline, they had a median duration of ILD of 1 (interquartile range 0.25–3.44) years, moderate or severe degree of dyspnoea (MMRC grade 2, 3 or 4) (40.3%), FVC (% of the predicted) mean (s.d.) 85.9 (21.8)%, DLCO (% of the predicted) 65.7 (18.3) and DAS28ESR 4.5 (1.5). The ILD patterns were: usual interstitial pneumonia (UIP) (40.3%), non-specific interstitial pneumonia (NSIP) (31.9%) and others (27.8%). ABA was prescribed at standard dose, i.v. (25.5%) or s.c. (74.5%). After a median follow-up of 12 (6–36) months the following variables did not show worsening: dyspnoea (MMRC) (91.9%); FVC (87.7%); DLCO (90.6%); and chest HRCT (76.6%). A significant improvement of DAS28ESR from 4.5 (1.5) to 3.1 (1.3) at the end of follow-up (P Conclusion ABA may be an effective and safe treatment for patients with RA-ILD.
- Published
- 2020
43. Omentin: a biomarker of cardiovascular risk in individuals with axial spondyloarthritis
- Author
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Esther Vicente, Virginia Portilla, María Paz Martínez-Vidal, David Castro-Corredor, Iván Ferraz-Amaro, Oreste Gualillo, Ricardo Blanco, Javier Rueda-Gotor, Juan Carlos Quevedo-Abeledo, Carlos Rodríguez-Lozano, Santos Castañeda, Alfonso Corrales, Sara Remuzgo-Martínez, Verónica Pulito-Cueto, Cristina Mata, Vanesa Hernández-Hernández, Raquel López-Mejías, Cristina Fernández-Carballido, Miguel A. González-Gay, Fernanda Genre, Javier Llorca, Joaquín Anino-Fernández, Verónica Mijares, Leticia Lera-Gómez, R. Expósito, and Universidad de Cantabria
- Subjects
Adult ,Male ,medicine.medical_specialty ,Linkage disequilibrium ,Molecular biology ,Science ,Adipokine ,Disease ,030204 cardiovascular system & hematology ,GPI-Linked Proteins ,Gastroenterology ,Inflammatory bowel disease ,Polymorphism, Single Nucleotide ,Article ,Linkage Disequilibrium ,03 medical and health sciences ,0302 clinical medicine ,Polymorphism (computer science) ,Risk Factors ,Internal medicine ,Lectins ,Spondylarthritis ,medicine ,Humans ,health care economics and organizations ,030203 arthritis & rheumatology ,Multidisciplinary ,business.industry ,Biological techniques ,Middle Aged ,medicine.disease ,Minor allele frequency ,Cardiovascular Diseases ,Case-Control Studies ,Cohort ,Biomarker (medicine) ,Cytokines ,Medicine ,Female ,business ,Biomarkers - Abstract
Cardiovascular (CV) disease is the main cause of mortality in axial spondyloarthritis (axSpA). CV risk is enhanced by dysregulation of adipokines. Low omentin levels were associated with metabolic dysfunction and CV disease in conditions different from axSpA. Accordingly, we evaluated the genetic and functional implication of omentin in CV risk and subclinical atherosclerosis in a cohort of 385 axSpA patients. Subclinical atherosclerosis was evaluated by carotid ultrasound. Omentin rs12409609, in linkage disequilibrium with a polymorphism associated with CV risk, was genotyped in 385 patients and 84 controls. Serum omentin levels were also determined. omentin mRNA expression was assessed in a subgroup of individuals. Serum and mRNA omentin levels were lower in axSpA compared to controls. Low serum omentin levels were related to male sex, obesity, inflammatory bowel disease (IBD) and high atherogenic index. rs12409609 minor allele was associated with low omentin mRNA expression in axSpA. No association was observed with subclinical atherosclerosis at the genetic or functional level. In conclusion, in our study low omentin serum levels were associated with CV risk factors in axSpA. Furthermore, rs12409609 minor allele may be downregulating the expression of omentin. These data support a role of omentin as a CV risk biomarker in axSpA. We wish to thank all the patients and controls that participated in this study. This work was supported by funds of a NEXT-VAL grant (NVAL17/10) (Instituto de Investigación Sanitaria IDIVAL) awarded to FG. SR-M is supported by funds of the RETICS Program (RD16/0012/0009) from the ‘Instituto de Salud Carlos III´ (ISCIII), co-funded by the European Regional Development Fund (ERDF). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). VM is supported by funds of a Miguel Servet type I programme (grant CP16/00033) (ISCIII, co-funded by the European Social Fund (ESF)). LL-G is supported by funds of PI18/00042 (ISCIII, co-funded by ERDF). RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, co-funded by the ESF (grant CP16/00033).
- Published
- 2020
44. Clinical Outcomes of Patients with COVID-19 and Chronic Inflammatory and Autoimmune Rheumatic Diseases: A Multicentric Matched-Cohort Study
- Author
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José Pablos, Maria Galindo, Loreto Carmona, Miriam Retuerto, Ana Lledó, Ricardo Blanco, Miguel A. González-Gay, David Martinez-Lopez, Isabel Castrejón, José M. Álvaro-Gracia, David Fernández-Fernández, Antonio Mera-Varela, Sara Manrique-Arija, Natalia Mena-Vázquez, Antonio Fernández-Nebro, and RIER Investigators Group
- Subjects
medicine.medical_specialty ,Prognostic variable ,business.industry ,Inflammatory arthritis ,Arthritis ,Disease ,medicine.disease ,Comorbidity ,Internal medicine ,Diabetes mellitus ,Cohort ,medicine ,business ,Cohort study - Abstract
Background: The impact of chronic inflammatory rheumatic diseases on COVID-19 severity is poorly known. Here we compare the outcomes of a cohort of rheumatic patients with a matched control cohort to identify potential risk factors for severe illness. Methods: In this comparative cohort study, we systematically identified hospital PCR+ COVID-19 rheumatic patients with chronic inflammatory arthritis (IA) or autoimmune/immunomediated diseases (AI/IMID). Non-rheumatic controls were randomly sampled 1:1, and matched by age, sex, and PCR date. The main outcome was severe COVID-19, defined as death, invasive ventilation, ICU admission, or serious complications. We assessed the association between the outcome and potential prognostic variables, adjusted by COVID treatment, using logistic regression. Findings: The cohorts were composed of 456 rheumatic and non-rheumatic patients, in equal numbers. Mean age was 63 [IQR 53-78] and male sex 41% in both cohorts. Rheumatic diseases were IA (60%) and AI/IMID (40%). Patients were on treatment with glucocorticoids (40%), conventional synthetic disease modifying antirheumatic drugs (csDMARD) (57%), targeted synthetic or biological (ts/bDMARD) (23%), or other immunosuppressants (12%). Most patients (74%) had been hospitalised, and the risk of severe COVID was 31·6% in the rheumatic and 28·1% in the non-rheumatic cohort. Ageing, male sex and previous comorbidity (obesity, diabetes, hypertension, cardiovascular, or lung disease) increased the risk in the rheumatic cohort by bivariate analysis. In logistic regression analysis, independent factors associated with severe were increased age (OR 5·31; CI 3·14-8·95), male sex (2·13; CI 1·35-3·36) and having an AI/IMID (OR 1·98; CI 1·15-3·41). Interpretation: In patients with chronic inflammatory rheumatic diseases aging, sex and having an AI/IMID but not IA nor previous immunosuppressive therapies were associated with severe COVID-19. Funding Statement: The RIER network was supported by Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III (RD16/0012 RETICS program) and cofinanced by the European Regional Development Fund. Declaration of Interests: None of the authors have competing interests to declare. Ethics Approval Statement: The study was approved by Comite de Etica de la Investigacion del Hospital Universitario 12 de Octubre, CEIm number: 20/160.
- Published
- 2020
45. Biologic Therapy in Refractory Non-Multiple Sclerosis Optic Neuritis Isolated or Associated to Immune Mediated Inflammatory Diseases. A Multicenter Study
- Author
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Santos Castañeda, Miguel A. González-Gay, José Luis Martín-Varillas, Iñigo Rúa-Figueroa, R. Demetrio-Pablo, Ricardo Blanco, Susana Romero-Yuste, O. Maiz-Alonso, D. Martínez-López, José L. Hernández, Alfonso Casado, Belén Atienza-Mateo, Ana Blanco, Julio Sánchez, Laura Cáceres-Martin, Norberto Ortego-Centeno, Diana Prieto-Peña, Carmen Álvarez-Reguera, José L. García-Serrano, P. Estrada, Esther Vicente, José Luis Callejas-Rubio, Javier Narváez, Alba Herrero-Morant, Vanesa Calvo-Río, and Universidad de Cantabria
- Subjects
medicine.medical_specialty ,genetic structures ,lcsh:Medicine ,Azathioprine ,Optic neuritis ,Gastroenterology ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Tocilizumab ,Neuritis ,Internal medicine ,medicine ,Relapsing polychondritis ,030203 arthritis & rheumatology ,Neuromyelitis optica ,business.industry ,Adrenocortical hormones ,lcsh:R ,Adalimumab ,Hydroxychloroquine ,General Medicine ,medicine.disease ,Corticosteroides ,Infliximab ,eye diseases ,chemistry ,Rituximab ,business ,030217 neurology & neurosurgery ,medicine.drug ,Biologic therapy - Abstract
We aimed to assess the efficacy of biologic therapy in refractory non-Multiple Sclerosis (MS) Optic Neuritis (ON), a condition more infrequent, chronic and severe than MS ON. This was an open-label multicenter study of patients with non-MS ON refractory to systemic corticosteroids and at least one conventional immunosuppressive drug. The main outcomes were Best Corrected Visual Acuity (BCVA) and both Macular Thickness (MT) and Retinal Nerve Fiber Layer (RNFL) using Optical Coherence Tomography (OCT). These outcome variables were assessed at baseline, 1 week, and 1, 3, 6 and 12 months after biologic therapy initiation. Remission was defined as the absence of ON symptoms and signs that lasted longer than 24 h, with or without an associated new lesion on magnetic resonance imaging with gadolinium contrast agents for at least 3 months. We studied 19 patients (11 women/8 men, mean age, 34.8 ±, 13.9 years). The underlying diseases were Bechet&rsquo, s disease (n = 5), neuromyelitis optica (n = 3), systemic lupus erythematosus (n = 2), sarcoidosis (n = 1), relapsing polychondritis (n = 1) and anti-neutrophil cytoplasmic antibody -associated vasculitis (n = 1). It was idiopathic in 6 patients. The first biologic agent used in each patient was: adalimumab (n = 6), rituximab (n = 6), infliximab (n = 5) and tocilizumab (n = 2). A second immunosuppressive drug was simultaneously used in 11 patients: methotrexate (n = 11), azathioprine (n = 2), mycophenolate mofetil (n = 1) and hydroxychloroquine (n = 1). Improvement of the main outcomes was observed after 1 year of therapy when compared with baseline data: mean ±, SD BCVA (0.8 ±, 0.3 LogMAR vs. 0.6 ±, 0.3 LogMAR, p = 0.03), mean ±, SD RNFL (190.5 ±, 175.4 &mu, m vs. 183.4 ±, 139.5 &mu, m, p = 0.02), mean ±, SD MT (270.7 ±, 23.2 &mu, m vs. 369.6 ±, 137.4 &mu, p = 0.03). Besides, the median (IQR) prednisone-dose was also reduced from 40 (10&ndash, 61.5) mg/day at baseline to. 2.5 (0&ndash, 5) mg/day after one year of follow-up, p = 0.001. After a mean ±, SD follow-up of 35 months, 15 patients (78.9%) achieved ocular remission, and 2 (10.5%) experienced severe adverse events. Biologic therapy is effective in patients with refractory non-MS ON.
- Published
- 2020
46. Association of circulating calprotectin with lipid profile in axial spondyloarthritis
- Author
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Sara Remuzgo-Martínez, C. Mata, Virginia Portilla, Alfonso Corrales, Oreste Gualillo, Ricardo Blanco, R. Expósito, Javier Rueda-Gotor, Miguel A. González-Gay, Verónica Mijares, Fernanda Genre, José L. Hernández, Javier Llorca, Raquel López-Mejías, and Universidad de Cantabria
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,endocrine system ,endocrine system diseases ,lcsh:Medicine ,Context (language use) ,Inflammation ,Gastroenterology ,Carotid Intima-Media Thickness ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Spondylarthritis ,medicine ,Humans ,heterocyclic compounds ,Axial spondyloarthritis ,lcsh:Science ,neoplasms ,health care economics and organizations ,Ultrasonography ,030203 arthritis & rheumatology ,Multidisciplinary ,medicine.diagnostic_test ,business.industry ,Incidence (epidemiology) ,Metabolic risk ,Cholesterol, HDL ,lcsh:R ,Carotid ultrasonography ,Middle Aged ,Atherosclerosis ,Lipids ,digestive system diseases ,030104 developmental biology ,C-Reactive Protein ,Carotid Arteries ,Female ,lcsh:Q ,Calprotectin ,medicine.symptom ,Lipid profile ,business ,Leukocyte L1 Antigen Complex ,Biomarkers - Abstract
Calprotectin (CPT) is released during inflammation, also in the context of atherosclerosis. The link between CPT and the atherosclerotic process was evaluated in several diseases. However, studies in axial spondyloarthritis (axSpA), associated with a high incidence of subclinical atherosclerosis, are scarce. Therefore, we assessed the association of CPT with subclinical atherosclerosis and metabolic risk factors in axSpA. CPT serum levels were measured by enzyme-linked immunosorbent assay in 163 axSpA patients and 63 controls. Subclinical atherosclerosis was determined in patients by carotid ultrasonography (assessing the presence/absence of carotid plaques and carotid intima-media thickness [cIMT]). Data on inflammation, disease activity, lipid profile and treatment were collected to evaluate its relationship with CPT. axSpA patients evidenced lower CPT levels than controls. CPT showed no association with plaques or cIMT in axSpA. CPT and HDL-cholesterol negatively correlated, while a positive association of CPT with the atherogenic index was disclosed. Additionally, axSpA patients with C-reactive protein values at diagnosis higher than 3?mg/L displayed higher CPT levels. Our study shows no relationship between CPT and markers of subclinical atherosclerosis in axSpA. Nevertheless, it demonstrates an association of CPT with adverse lipid profiles and inflammatory biomarkers, which could further influence on the development of atherosclerosis. We wish to thank all the patients and controls that participated in this study and Begoña Ubilla for technical assistance. FG is a recipient of a Sara Borrell post-doctoral fellowship from the Instituto de Salud Carlos III (ISCIII) (Spain), co-funded by the European Social Fund (ESF, “Investing in your future”) (grant CD15/00095). SR-M is supported by funds of the RETICS Program (RIER) RD16/0012/0009 (ISCIII, co-funded by the European Regional Development Fund, ERDF). VM is supported by funds of a Miguel Servet type I programme (grant CP16/00033) (ISCIII, co-funded by ERDF). RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, co-funded by the ESF (grant CP16/00033). This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
- Published
- 2018
47. Drug therapies for polymyalgia rheumatica: a pharmacotherapeutic update
- Author
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Ricardo Blanco, Trinitario Pina, Santos Castañeda, Diana Prieto-Peña, Miguel A. González-Gay, and Monica Calderón-Goercke
- Subjects
musculoskeletal diseases ,0301 basic medicine ,Drug ,medicine.medical_specialty ,media_common.quotation_subject ,education ,MEDLINE ,Polymyalgia rheumatica ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,Prednisone ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,skin and connective tissue diseases ,Retrospective Studies ,media_common ,030203 arthritis & rheumatology ,Pharmacology ,business.industry ,Retrospective cohort study ,General Medicine ,medicine.disease ,Inflammatory pain ,030104 developmental biology ,medicine.anatomical_structure ,Polymyalgia Rheumatica ,Shoulder girdle ,Methotrexate ,business ,medicine.drug - Abstract
Polymyalgia rheumatica (PMR), a common disease in individuals older than 50 in the western world, is characterized by bilateral inflammatory pain involving the shoulder girdle and less commonly the neck and pelvic girdle. The main goals of the currently available treatment are to induce remission and prevent relapse.This review briefly presents the main epidemiological and clinical features of PMR and discusses in depth both its classical management as well as new therapies used in PMR.In general, patients with isolated PMR experience a rapid response (in less than seven days) to 12.5-25 mg/prednisone/day. Methotrexate is the conventional disease-modifying antirheumatic drug most commonly used for disease management, especially for relapses of the disease. However, this agent often yields a modest effect. Randomized controlled trials do not support the use of antitumor necrosis factor agents in PMR. Several case series and retrospective studies have highlighted the efficacy of the anti-interleukin-6 receptor antibody tocilizumab in PMR. However, controlled trials are needed to fully establish the efficacy of this biologic agent in PMR. The potential beneficial effect of the Janus-kinase inhibitors remains to be determined.
- Published
- 2018
48. Disease Activity Influences Cardiovascular Risk Reclassification Based on Carotid Ultrasound in Patients with Psoriatic Arthritis
- Author
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Alfonso Corrales, Miguel A. González-Gay, Virginia Portilla-Gonzalez, Susana Armesto, Iván Ferraz-Amaro, José L. Hernández, Natalia Palmou-Fontana, Ricardo Blanco, Marcos A González-López, Fernanda Genre, Javier Llorca, D. Martínez-López, Javier Rueda-Gotor, Juan Carlos Quevedo-Abeledo, and Universidad de Cantabria
- Subjects
0301 basic medicine ,Carotid ultrasound ,medicine.medical_specialty ,Inflammatory arthritis ,Psoriatic Arthritis ,Immunology ,Disease ,Carotid Intima-Media Thickness ,Disease activity ,03 medical and health sciences ,Psoriatic arthritis ,0302 clinical medicine ,Rheumatology ,Risk Factors ,Internal medicine ,medicine ,Immunology and Allergy ,Humans ,In patient ,Ultrasonography ,030203 arthritis & rheumatology ,medicine.diagnostic_test ,business.industry ,Arthritis, Psoriatic ,Statin treatment ,medicine.disease ,030104 developmental biology ,Cross-Sectional Studies ,Carotid Plaques ,Cardiovascular Diseases ,Heart Disease Risk Factors ,Cardiovascular Risk Score ,business ,Lipid profile - Abstract
Objective. Because the addition of carotid ultrasound (US) into composite cardiovascular (CV) risk scores has been found effective for identifying patients with inflammatory arthritis and high CV risk, we aimed to determine whether its use would facilitate the reclassification of patients with psoriatic arthritis (PsA) into the very high Systematic Coronary Risk Evaluation (SCORE) risk category and whether this might be related to disease features. Methods. This was a cross-sectional study involving 206 patients who fulfilled ClASsification for Psoriatic ARthritis criteria for PsA, and 179 controls. We assessed lipid profile, SCORE, disease activity measurements, and the presence of carotid plaques and carotid intima-media thickness by ultrasonography. A multivariable regression analysis, adjusted for classic CV risk factors, was performed to evaluate whether the risk of reclassification could be explained by disease-related features and to assess the most parsimonious combination of risk reclassification predictors. Results. Forty-seven percent of patients were reclassified into a very high SCORE risk category after carotid US compared to 26% of controls (p < 0.001). Patients included in the low SCORE risk category were those who were more commonly reclassified (30% vs 14%, p = 0.002). The Disease Activity Index for PsA (DAPSA) score was associated with reclassification (? 1.10, 95% CI 1.02?1.19; p = 0.019) after adjusting for age and traditional CV risk factors. A model containing SCORE plus age, statin use, and DAPSA score yielded the highest discriminatory accuracy compared to the SCORE-alone model (area under the receiver-operating characteristic curve 0.863, 95% CI 0.789?0.936 vs 0.716, 95% CI 0.668?0.764; p < 0.001). Conclusion. Patients with PsA are more frequently reclassified into the very high SCORE risk category following carotid US assessment than controls. This was independently explained by the disease activity. Funding: This work was supported by a grant to I.F-A. from the Spanish Ministry of Health, Subdirección General de Evaluación y Fomento de la Investigación, Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 and by Fondo Europeo de Desarrollo Regional -FEDER - (Fondo de Investigaciones Sanitarias, FIS PI14/00394, PI17/00083) Professor González-Gay research was supported by European Union FEDER funds and by the “Fondo de Investigación Sanitaria” (grants PI06/0024, PS09/00748, PI12/00060, PI15/00525 and PI18/00043) of the ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). It was also partially supported by RETICS Programs RD12/0009 (RIER), RD12/0009/0013 and RD16/0012 from the ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain).
- Published
- 2019
49. Anti-interleukin 6 receptor tocilizumab in refractory uveitis associated with Behçet’s disease: multicentre retrospective study
- Author
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N. Vegas-Revenga, Carmen Carrasco-Cubero, Elia Valls-Pascual, José Luis Martín-Varillas, Miguel A. González-Gay, María Carmen González-Vela, José L. Hernández, Vanesa Calvo-Río, Emma Beltrán, Javier Loricera, L Domínguez-Casas, C. Fernández-Díaz, Antonio Atanes, Belén Atienza-Mateo, Ricardo Blanco, Miguel Cordero-Coma, Marisa Hernández-Garfella, Joan M. Nolla, R. Demetrio-Pablo, Lucía Martínez-Costa, and Natalia Palmou-Fontana
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Adolescent ,anti-TNF therapy ,Behcet's disease ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,Etanercept ,Uveitis ,Young Adult ,tocilizumab ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Tocilizumab ,Rheumatology ,Internal medicine ,medicine ,Adalimumab ,Humans ,Pharmacology (medical) ,Child ,Aged ,Retrospective Studies ,030203 arthritis & rheumatology ,business.industry ,Retinal vasculitis ,Behcet Syndrome ,Remission Induction ,Middle Aged ,medicine.disease ,Receptors, Interleukin-6 ,eye diseases ,Infliximab ,Golimumab ,Treatment Outcome ,chemistry ,uveitis ,030221 ophthalmology & optometry ,Female ,business ,Follow-Up Studies ,medicine.drug - Abstract
Objective: To assess the efficacy of tocilizumab (TCZ) in refractory uveitis of Behcet's disease (BD). Methods: Multicentre study of patients with BD-associated uveitis. Patients were refractory to conventional and biologic immunosuppressive drugs. The main outcome measures were intraocular inflammation, macular thickness, visual acuity and corticosteroid-sparing effects. Results: We studied 11 patients (7 men) (20 affected eyes); median age 35 years. Uveitis was bilateral in nine patients. The patterns of ocular involvement were panuveitis (n = 8, with retinal vasculitis in 4), anterior uveitis (n = 2) and posterior uveitis (n = 1). Cystoid macular oedema was present in seven patients. The clinical course was recurrent (n = 7) or chronic (n = 4). Before TCZ, patients had received systemic corticosteroids, conventional immunosuppressants and the following biologic agents: adalimumab (n = 8), infliximab (n = 4), canakimumab (n = 1), golimumab (n = 3), etanercept (n = 1). TCZ was used as monotherapy or combined with conventional immunosuppressants at 8 mg/kg/i.v./4 weeks (n = 10) or 162mg/s.c./week (n = 1). At TCZ onset the following extraocular manifestations were present: oral and/or genital ulcers (n = 7), arthritis (n = 4), folliculitis/pseudofolliculitis (n = 4), erythema nodosum (n = 2), livedo reticularis (n = 1) and neurological involvement (n = 2). TCZ yielded rapid and maintained improvement in all ocular parameters of the patients, with complete remission in eight of them. However, this was not the case for the extraocular manifestations, since TCZ was only effective in three of them. After a mean (S.D.) follow-up of 9.5 (8.05) months, TCZ was withdrawn in two cases, due to a severe infusion reaction and arthritis impairment, respectively. Conclusion: TCZ could be a therapeutic option in patients with BD and refractory uveitis.
- Published
- 2018
50. Efficacy, safety, and tolerability of secukinumab in patients with active ankylosing spondylitis: a randomized, double-blind phase 3 study, MEASURE 3
- Author
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Aimee Readie, Luminita Pricop, Marco Maradiaga, Brian Porter, Ricardo Blanco, Eva Dokoupilova, Alan Kivitz, Mats Andersson, Karel Pavelka, and Hasan Tahir
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,lcsh:Diseases of the musculoskeletal system ,Injections, Subcutaneous ,Phases of clinical research ,Antibodies, Monoclonal, Humanized ,Placebo ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Internal medicine ,Clinical endpoint ,medicine ,Humans ,Spondylitis, Ankylosing ,Secukinumab ,030203 arthritis & rheumatology ,Ankylosing spondylitis ,Dose-Response Relationship, Drug ,business.industry ,Interleukin-17 ,Antibodies, Monoclonal ,Repeated measures design ,Middle Aged ,medicine.disease ,Regimen ,IL-17 ,030104 developmental biology ,Tolerability ,Antirheumatic Agents ,Administration, Intravenous ,Female ,lcsh:RC925-935 ,business ,Research Article ,Biologic therapy - Abstract
Background Secukinumab, an anti–interleukin-17A monoclonal antibody, improved the signs and symptoms of ankylosing spondylitis (AS) in two phase 3 studies (MEASURE 1 and MEASURE 2). Here, we present 52-week results from the MEASURE 3 study assessing the efficacy and safety of secukinumab 300 and 150 mg subcutaneous maintenance dosing, following an intravenous loading regimen. Methods A total of 226 patients were randomized to intravenous secukinumab 10 mg/kg (baseline, weeks 2 and 4) followed by subcutaneous secukinumab 300 mg (IV-300 mg) or 150 mg (IV-150 mg) every 4 weeks, or matched placebo. Patients in the placebo group were re-randomized to subcutaneous secukinumab at a dose of 300 or 150 mg at week 16. The primary endpoint was the Assessment of SpondyloArthritis international Society criteria for 20% improvement (ASAS20) response rate at week 16 in the IV-300 mg or IV-150 mg versus placebo. Other endpoints assessed through week 52 included improvements in ASAS40, ASAS 5/6, Bath Ankylosing Spondylitis Disease Activity Index, and ASAS partial remission responses, as well as the change from baseline in high-sensitivity C-reactive protein levels. Statistical analyses followed a predefined hierarchical hypothesis testing strategy to adjust for multiplicity of testing, with non-responder imputation used for binary variables and mixed-model repeated measures for continuous variables. Results The primary efficacy endpoint was met; the ASAS20 response rate was significantly greater at week 16 in the IV-300 mg (60.5%; P
- Published
- 2017
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