Search

Objective: Aortitis in Giant Cell Arteritis (GCA-aortitis) is a frequent complication that may lead to aneurysms. Tocilizumab (TCZ) was approved in GCA, but the efficacy in GCA-aortitis and aneurysms has not been analyzed to date. Our aim was to assess the effectiveness and safety of TCZ in a wide series of GCA-aortitis and aneurysms., Methods: Multicentre observational study with GCA-aortitis treated with TCZ. GCA was diagnosed by: a) ACR criteria, b) temporal artery biopsy, and/or c) imaging techniques. Aortitis was diagnosed mainly by PET/CT. Main outcomes were EULAR and imaging remission. Others were clinical remission, analytical normalization, corticosteroid-sparing effect, and the prevention and improvement of aneurysms., Results: 196 patients with GCA-aortitis treated with TCZ. After 6 months, 72.2% reached EULAR remission but only 12% an imaging remission; increasing up-to 81.4% and 31.8%, respectively, at 24 months. A rapid clinical remission, ESR and CRP normalization was observed in 47.4%, 84.3% and 55.6%, at 1 month, increasing to 89.6%, 85.3% and 80.3% at 24 months, respectively. Aneurysms were present in 10 (5%) patients. Five of them required early surgery, while 3 others enlarged. No patient on TCZ therapy developed aneurysms during follow-up., Conclusion: In patients with GCA-aortitis treated with TCZ, a rapid and maintained clinical and analytical improvement was observed. However, there was an uncoupling between clinical and EULAR remission with imaging remission., Competing Interests: Declaration of competing interest Disclosures that might be interpreted as constituting possible conflict(s) of interest for the study: Javier Loricera had consultation fees/participation in company-sponsored speaker´s bureau from Roche, Galápagos, Novartis, UCB Pharma, MSD, Celgene, Astra Zeneca, and Grünenthal and received support for attending meetings and/or travel from Janssen, Abbvie, Roche, Novartis, MSD, UCB Pharma, Celgene, Lilly, Pfizer, Galápagos. Paloma Vela research funding/consulting and conferences fees from: Abbvie, Roche, Amgen, Novartis, Lilly, Pfizer, GSK. Susana Romero-Yuste has received grants/recents supports from Abbvie, Astra-Zeneca, Bristol, Janssen, Lilly, Roche, Sandoz, Sanofi, UCB. Eugenio De Miguel Research funding/consulting and conferences fees from: Abbvie, Novartis, Pfizer, Roche, Janssen, Lilly, MSD, BMS, UCB, Grünenthal and Sanofi. Iván Ferraz-Amaro would like to acknowledge that he has received grants/research supports from Abbvie, MSD, Janssen, and Roche, as well as consultation fees from company sponsored speakers bureaus associated with Abbvie, Pfizer, Roche, Sanofi, Celgene, and MSD. Fernando López-Gutiérrez received support for attending meetings and/or travel from Janssen, Abbvie, Roche, Novartis, MSD, UCB Pharma, Celgene, Lilly, Pfizer, Galápagos. Santos Castañeda has received research support from MSD and Pfizer and had consultation fees/participation in company-sponsored speaker's bureau from BMS, Eli-Lilly, Roche, Gedeon-Richter, Grünenthal Pharma and UCB. Ricardo Blanco received grants/research support from AbbVie, MSD, and Roche, and had consultation fees/participation in a company-sponsored speaker's bureau from AbbVie, Pfizer, Roche, GSK, Lilly, UCB, Bristol-Myers, Novartis, Janssen, UCB and MSD. The following authors did not declare financial disclosure: Adrián Martín-Gutiérrez, Javier Narváez, Vicente Aldasoro, Olga Maiz, Eva Galíndez-Agirregoikoa, Jesús C. Fernández-López, Julio Sánchez-Martín, Patricia Moya, Cristina Campos., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: A substantial proportion of patients with giant cell arteritis (GCA) relapse despite standard therapy with glucocorticoids, methotrexate and tocilizumab. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway is involved in the pathogenesis of GCA and JAK inhibitors (JAKi) could be a therapeutic alternative. We evaluated the effectiveness of JAKi in relapsing GCA patients in a real-world setting and reviewed available literature., Methods: Retrospective analysis of GCA patients treated with JAKi for relapsing disease at thirteen centers in Spain and one center in United States (01/2017-12/2022). Outcomes assessed included clinical remission, complete remission and safety. Clinical remission was defined as the absence of GCA signs and symptoms regardless of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values. Complete remission was defined as the absence of GCA signs and symptoms along with normal ESR and CRP values. A systematic literature search for other JAKi-treated GCA cases was conducted., Results: Thirty-five patients (86% females, mean age 72.3) with relapsing GCA received JAKi therapy (baricitinib, n = 15; tofacitinib, n = 10; upadacitinib, n = 10). Before JAKi therapy, 22 (63%) patients had received conventional synthetic immunosuppressants (e.g., methotrexate), and 30 (86%) biologics (e.g., tocilizumab). After a median (IQR) follow-up of 11 (6-15.5) months, 20 (57%) patients achieved and maintained clinical remission, 16 (46%) patients achieved and maintained complete remission, and 15 (43%) patients discontinued the initial JAKi due to relapse (n = 11 [31%]) or serious adverse events (n = 4 [11%]). A literature search identified another 36 JAKi-treated GCA cases with clinical improvement reported for the majority of them., Conclusions: This real-world analysis and literature review suggest that JAKi could be effective in GCA, including in patients failing established glucocorticoid-sparing therapies such as tocilizumab and methotrexate. A phase III randomized controlled trial of upadacitinib is currently ongoing (ClinicalTrials.gov ID NCT03725202)., (© 2024. The Author(s).)

Scurvy is a nutritional disease caused by ascorbic acid (vitamin C) deficiency. Althought currently it is a rare disease, we should considerer it in the differential diagnosis of purpura and arthritis in patients with restrictive diets. We present the case of a 49-year-old man with a history of a nutritional disorder presented to our hospital with generalized purpura and hemarthros. Following the anamnesis and laboratory findings, rheumatological, infectious and hematological etiologies were excluded. Finally, the diagnosis of scurvy was made upon demostration poor levels of vitamin C and a spectacular response to nutritional supplements. We compare this case with 19 similar cases reported in the medical literature., (Copyright © 2024 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Objectives: Since interleukin-6 (IL-6) is a pivotal proinflammatory cytokine implicated in the pathogenesis of giant cell arteritis (GCA), we aimed to determine the potential association of the functional IL6 -174 G/C polymorphism with GCA as well as if the single base change variation at the promoter region in the human IL-6 gene may account for differences in the clinical spectrum of GCA between cranial and extracranial large vessel vasculitis (LVV)-GCA., Methods: The IL6 -174 G/C polymorphism (rs1800795) was genotyped in 191 patients with biopsy-proven GCA who had typical cranial manifestations of the disease, 109 patients with extracranial LVV-GCA, without cranial ischaemic manifestations of GCA, and 877 ethnically matched unaffected controls. A comparative study was carried out between patients with cranial and extracranial LVV-GCA and controls., Results: No significant differences in genotype and allele frequencies of IL6 -174 G/C polymorphism were found between the whole cohort of GCA patients and healthy controls. It was also the case when cranial and extracranial LVV-GCA were compared or when each of these subgroups was compared to controls. Moreover, no significant results in genotype and allele frequencies of IL6 -174 G/C polymorphism were disclosed when the whole cohort of GCA patients were stratified according to the presence of polymyalgia rheumatica, severe ischaemic manifestations, including permanent visual loss and peripheral arteriopathy, and HLA-DRB1*04:01 status., Conclusions: Our results show that the IL6 -174 G/C polymorphism does not influence the phenotypic expression of GCA.

Objectives: Tocilizumab (TCZ) is the only biologic therapy approved for giant cell arteritis (GCA). There is general agreement on the initial/maintenance dose, duration of TCZ therapy is not well established. In GiACTA trial, after one year on TCZ, most patients had GCA relapse after withdrawal. The aim of this study is to assess the effectiveness and safety of TCZ therapy optimisation in a large unselected series of patients with GCA in a clinical practice scenario., Methods: We carried out a multicentre study on 471 GCA patients treated with TCZ. Once prolonged remission was achieved (n=231) and based on a decision between patient and physician, TCZ was optimised (n=125). We compared optimised (TCZOPT) and not optimised (TCZNON-OPT) groups. Prolonged remission defined as normalisation of clinical and laboratory data for 6 months. Optimisation was carried out by decreasing TCZ dose and/or increasing dosing interval., Results: We evaluated 231 GCA patients on TCZ in prolonged remission. At TCZ onset, no differences in demographic, clinical, or laboratory data were observed. First TCZ optimisation was performed after a median follow-up of 12[6-17] months. Intravenous TCZ was optimised from 8 to 4mg/kg/4weeks in 44% patients, while subcutaneous TCZ was optimised from 162mg/w to 162mg/every-other-week in 65% cases. At the end of follow-up, prolonged remission (78.2% vs. 84.2%; p=0.29) and relapses (5.6% vs. 10.4%, p=0.177) were similar in TCZOPT vs. TCZNON-OPT. Severe infections were more frequent in TCZNON-OPT (12.9% vs. 6.6%; p=0.009)., Conclusions: TCZ optimisation may be done once complete remission is achieved by reducing dose or increasing dosing interval. This seems to be effective, safe and cost-effective therapeutic scheme.

Objectives: Two main different clinical phenotypes of giant cell arteritis (GCA) have been described, the classic cranial pattern and the extracranial large-vessel (LV) pattern. Since interferon gamma (IFNG) has shown to be a pivotal cytokine in the pathophysiology of GCA, our aim was to evaluate for the first time the influence of IFNG and IFNG receptor 1 (IFNGR1) polymorphisms in the different clinical phenotypes of GCA., Methods: Two IFNG polymorphisms (rs2069718 G/A and rs1861493 A/G) and one polymorphism in IFNGR1 (rs1327474 G/A) were genotyped in 191 patients with biopsy-proven cranial GCA, 109 with extracranial LV-GCA and 490 healthy controls. A comparative study was conducted between patients with cranial and extracranial LV-GCA., Results: No significant differences in genotype, allele, and haplotype frequencies of IFNG polymorphisms were found between GCA patients with the classic cranial pattern and the extracranial LV-GCA pattern. Similar results were found for genotype and allele frequencies of IFNGR1 polymorphism. It was also the case when patients with extracranial LV-GCA were compared with healthy controls., Conclusions: Our results show that IFNG and IFNGR1 polymorphisms do not influence the clinical phenotype of expression of GCA. Classic cranial GCA and extracranial LV-GCA seem to share a genetic pattern of IFNG pathway.

Objectives: To evaluate effectiveness and safety of certolizumab pegol (CZP) in uveitis due to immune-mediated inflammatory diseases (IMID)., Methods: Multicentre study of CZP-treated patients with IMID uveitis refractory to conventional immunosuppressant. Effectiveness was assessed through the following ocular parameters: best-corrected visual acuity, anterior chamber cells, vitritis, macular thickness and retinal vasculitis. These variables were compared between the baseline, and first week, first, third, sixth months, first and second year., Results: We studied 80 (33 men/47 women) patients (111 affected eyes) with a mean age of 41.6±11.7 years. The IMID included were: spondyloarthritis (n=43), Behçet's disease (n=10), psoriatic arthritis (n=8), Crohn's disease (n=4), sarcoidosis (n=2), juvenile idiopathic arthritis (n=1), reactive arthritis (n=1), rheumatoid arthritis (n=1), relapsing polychondritis (n=1), CONCLUSIONS: CZP seems to be effective and safe in uveitis related to different IMID, even in patients refractory to previous biological drugs., Competing Interests: Competing interests: JLM-V received grants/research support from AbbVie, Pfizer, Lilly, Celgene, Janssen, and UCB Pharma. VC-R received grants/research support from MSD and Roche and had consultation fees/participation in the company-sponsored speaker’s bureau from AbbVie, Lilly, Celgene, Grünenthal and UCB Pharma. LS-B received grants/research support from Roche, Lilly and Pfizer. EB-C had consultation fees/participation in the company-sponsored speaker’s bureau from AbbVie, Amgen, Janssen, MSD, Pfizer, Lilly, Novartis y UCB. PF received grants/research supports from Sobi and Novartis and had consultation fees/participation in the company-sponsored speaker’s bureau from Sobi and Novartis. AGM received consultation fees from Novartis and Amgem and sponsored speaker’s bureau from Novartis, Jansen, Amgen, UCB and Grünenthal. MC-C was a lecturer for AbbVie, Merck Sharp & Dohme, Allergan and UCB. He also participated in Advisory Boards for AbbVie and Allergan. He also had travel grants from AbbVie, UCB and Allergan. RV had consultation fees/participation in the company-sponsored speaker’s bureau from AbbVie, Pfizer, MSD, UCB, Gebro, Celgene, Janssen, Bristol Myers, Lilly, Galápagos, Amgen. CF-C received honoraria for lectures/presentations from AbbVie, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer and UCB; consulting fees from AbbVie, Janssen, Lilly, Novartis and UCB and support for attending meetings from AbbVie, Galapagos, Janssen, Lilly, Novartis, Roche and UCB. JLH received grants/research support from Amgen and participation in company-sponsored speaker’s bureau from Amgen, MSD and Novartis. RB received grants/research support from AbbVie, MSD and Roche, and had consultation fees/participation in a company-sponsored speaker’s bureau from AbbVie, Pfizer, Roche, Bristol Myers, Janssen and MSD., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: While treat-to-target (T2T) is endorsed for the management of rheumatoid arthritis (RA), data on the degree of implementation in clinical practice are limited. This study investigated the use of T2T for RA in a real-world setting across Europe., Methods: The Adelphi RA Disease-Specific Programme was a point-in-time survey of rheumatologists and their consulting patients with RA conducted between January and October 2020 in Belgium, France, Germany, Italy, Spain and the UK. Rheumatologists completed an attitudinal survey, and a record form for their next 10-12 consulting patients, who were invited to voluntarily complete a patient-reported questionnaire. Data collected included clinical characteristics, treatment patterns and attitudes towards T2T., Results: Overall, 316 rheumatologists provided data for 3120 patients, of whom 1108 completed the questionnaire. While 86.1% of rheumatologists estimated using T2T principles in clinical practice, only 66.6% of patients were reported by their physician to be managed using a T2T approach. Achieving disease remission was the most commonly reported treatment goal identified by rheumatologists (79.7%), followed by symptom control (47.8%) and reducing impact on quality of life (44.5%). 40.8% of rheumatologists and their patients were in agreement that a treatment goal had been set. When there was agreement on treatment goals, we observed better patient satisfaction, engagement and treatment success., Conclusions: Despite recommendations, the T2T approach in RA appears to be suboptimally implemented in clinical practice. This highlights the importance of patient-centricity in the decision-making process to define meaningful targets and select appropriate treatments to improve disease outcomes., Competing Interests: Competing interests: PCT has received research grants and/or consultation fees from Galapagos, AbbVie, Biogen, Gilead, GlaxoSmithKline, Janssen, Novartis, Lilly, Pfizer, Roche, Sanofi, Nordic Pharma, Fresenius and UCB. BF has received research grants from AbbVie, Lilly, MSD and Pfizer, and consultancy fees from AbbVie, Amgen, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Fresenius Kabi, Gilead, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, Sobi and UCB. YP has received consultancy fees from AbbVie, Galapagos, Grünenthal, Lilly, Novartis, Janssen and Sandoz. SR-Y has been paid as a speaker by AbbVie, Amgen, Bristol Myers Squibb, Grunenthal, Janssen, Kern Pharma, Lilly, Roche, Sandoz, Sanofi and UCB; been a paid consultant for AbbVie, Bristol, Biogen, Fresenius, Galapagos, Gebro, Janssen and Lilly; and received grant/research support from Bristol Myers Squibb, MSD, Novartis and Pfizer. JB has received consultancy fees from Galapagos, Gilead, Novartis, Astra Zeneca and UCB. MW has received research support from AbbVie, Actelion, Boehringer, Galapagos, Gilead, GSK, Hexal, Novartis and UCB; consultancy fees from AbbVie, Boehringer, BMS, Celgene, Galapagos, Gilead, GSK, Medac, Mylan, Novartis, Pfizer, Sanofi and UCB; and speaker fees from AbbVie, Aescu, Amgen, Biogen, BMS, Berlin Chemie, GSK, Hexal, Janssen, Medac, MSD, Mundipharma, Mylan, Novartis, Pfizer, Riemser, Sanofi and UCB. OH is an employee of Adelphi Real World. ER is an employee of Adelphi Real World. MZ is an employee and shareholder of Galapagos NV. KVB is an employee and shareholder of Galapagos NV. RC has been paid as a speaker for AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Fresenius Kabi, Galapagos, Gilead, Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi and UCB, and worked as a paid consultant for Galapagos, Gilead, Janssen, Lilly and MSD. RA has received advisory fees from AbbVie, Amgen, Biogen, BMS, Celltrion, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer and Roche., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To assess efficacy and safety of biologic therapy (BT) in neurobehçet's disease (NBD) refractory to glucocorticoids and at least one conventional immunosuppressive drug., Methods: Open-label, national, multicentre study. NBD diagnosis was based on the International Consensus Recommendation criteria. Outcome variables were efficacy and safety. Main efficacy outcome was clinical remission. Other outcome variables analysed were glucocorticoid-sparing effect and improvement in laboratory parameters., Results: We studied 41 patients [21 women; age 40.6 (10.8) years]. Neurological damage was parenchymal (n = 33, 80.5%) and non-parenchymal (n = 17, 41.5%). First BTs used were infliximab (n = 19), adalimumab (n = 14), golimumab (n = 3), tocilizumab (n = 3) and etanercept (n = 2). After 6 months of BT, neurological remission was complete (n = 23, 56.1%), partial (n = 15, 37.6%) and no response (n = 3, 7.3%). In addition, median (IQR) dose of oral prednisone decreased from 60 (30-60) mg/day at the initial visit to 5 (3.8-10) mg/day after 6 months (P < 0.001). It was also the case for mean erythrocyte sedimentation rate [31.5 (25.6)-15.3 (11.9) mm/1st h, P = 0.011] and median (IQR) C-reactive protein [1.4 (0.2-12.8) to 0.3 (0.1-3) mg/dl, P = 0.001]. After a mean follow-up of 57.5 months, partial or complete neurological remission persisted in 37 patients (90.2%). BT was switched in 22 cases (53.6%) due to inefficacy (n = 16) or adverse events (AEs) (n = 6) and discontinued due to complete prolonged remission (n = 3) or severe AE (n = 1). Serious AEs were observed in two patients under infliximab treatment., Conclusions: BT appears to be effective and relatively safe in refractory NBD., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Visual involvement is the most feared complication of giant cell arteritis (GCA). Information on the efficacy of tocilizumab (TCZ) for this complication is scarce and controversial., Objective: We assessed a wide series of GCA treated with TCZ, to evaluate its role in the prevention of new visual complications and its efficacy when this manifestation was already present before the initiation of TCZ., Design: This is an observational multicenter study of patients with GCA treated with TCZ., Methods: Patients were divided into two subgroups according to the presence or absence of visual involvement before TCZ onset. Visual manifestations were classified into the following categories: transient visual loss (TVL), permanent visual loss (PVL), diplopia, and blurred vision., Results: Four hundred seventy-one GCA patients (mean age, 74 ± 9 years) were treated with TCZ. Visual manifestations were observed in 122 cases (26%), of which 81 were present at TCZ onset: PVL ( n  = 60; unilateral/bilateral: 48/12), TVL ( n  = 17; unilateral/bilateral: 11/6), diplopia ( n  = 2), and blurred vision ( n  = 2). None of the patients without previous visual involvement or with TVL had new episodes after initiation of TCZ, while only 11 out of 60 (18%) patients with PVL experienced some improvement. The two patients with diplopia and one of the two patients with blurred vision improved., Conclusion: TCZ may have a protective effect against the development of visual complications or new episodes of TVL in GCA. However, once PVL was established, only a few patients improved., Competing Interests: Competing interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Disclosures that might be interpreted as constituting of possible conflict(s) of interest for the study: J. Loricera had consultation fees/participation in company-sponsored speaker’s bureau from Roche, Novartis, UCB Pharma, MSD, Celgene, and Grünenthal and received support for attending meetings and/or travel from Janssen, AbbVie, Roche, Novartis, MSD, UCB Pharma, Celgene, Lilly, Pfizer, Galápagos. S. Castañeda is assistant professor of the UAM-Roche, EPID-Future chair, Department of Medicine, Universidad Autónoma de Madrid, Madrid, Spain, and received support for attending meetings and/or travel from Janssen, AbbVie, Roche, Novartis, MSD, UCB Pharma, Celgene, Lilly, Pfizer. V. Aldasoro had consultation fees/participation in company sponsored speaker’s bureau from Janssen, BMS, MSD, Roche, Sanofi, Pfizer, Novartis, Amgen, Lilly, AbbVie, Gebro, Nordic, Lacer, Alter, UCB, ASAC Pharma, Menarini and Celgene and received support for attending meetings and/or travel from Janssen, BMS, MSD, Roche, Sanofi, Pfizer, Novartis, Amgen, Lilly, AbbVie, Gebro, Nordic, Lacer, Alter, UCB, ASAC Pharma, Menarini, and Celgene. O. Maiz received support for attending meetings and/or travel from Janssen, AbbVie, Roche, Novartis, MSD, UCB Pharma, Celgene, Lilly, Pfizer. P. Vela received grants/research supports from AbbVie, Pfizer, BMS, Novartis, MSD, and Roche and had consultation fees/participation in company sponsored speaker’s bureau from Pfizer, BMS, Lilly, UCB, and MSD and received support for attending meetings and/or travel from Pfizer, BMS, Lilly, UCB, and MSD. S. Romero-Yuste had consultation fees/participation in company sponsored speaker’s bureau from AbbVie, Astra-Zeneca, BMS, Fresenius, Janssen, K. Pharma, Lilly, MSD, Novartis, Pfizer, Roche, Rubió, Sandoz, Sanofi, UCB and attendance at conferences AbbVie, Astra-Zeneca, BMS, Fresenius, Janssen, K. Pharma, Lilly, MSD, Novartis, Pfizer, Roche, Rubió, Sandoz, Sanofi, UCB. E. de Miguel had consultation fees/participation in company sponsored speaker’s bureau from AbbVie, Novartis, Pfizer, BMS, MSD, UCB, Roche, Grünenthal, and Janssen and received support for attending meetings and/or travel from AbbVie, Novartis, Pfizer, BMS, MSD, UCB, Roche, Grünenthal, and Janssen. E. Galíndez-Agirregoikoa had consultation fees/participation in company sponsored speaker’s bureau from Celgene, AbbVie, Pfizer, Roche, Lilly, MSD, Janssen, and Bristol and received support for attending meetings and/or travel from Celgene, AbbVie, Pfizer, Roche, Lilly, MSD, Janssen, and Bristol. F. Sivera received grants from Roche. Iván Ferraz-Amaro received grants/research supports from AbbVie, MSD, Janssen, and Roche and received consultation fees from company-sponsored speaker’s bureau associated with AbbVie, Pfizer, Roche, Sanofi, Sobi, Amgen, Celgene, and MSD and received support for attending meetings and/or travel from AbbVie, Pfizer, Roche, Sanofi, Sobi, Amgen, Celgene, and MSD. Mónica Calderón-Goercke received support for attending meetings and/or travel from Lilly, AbbVie, Pfizer. José L. Hernández received grants from Amgen and had participation in company-sponsored speaker’s bureau from Amgen, MSD, Bayer, and Esteve. Miguel A. Gonzalez-Gay has received grants/research supports from AbbVie, MSD, Janssen, and Roche and had consultation fees/participation in company-sponsored speaker’s bureau from AbbVie, Pfizer, Roche, Sanofi, Lilly, Celgene, and MSD and received support for attending meetings and/or travel from AbbVie, Pfizer, Roche, Sanofi, Lilly, Celgene, and MSD. R. Blanco received grants/research supports from AbbVie, MSD, and Roche, and had consultation fees/participation in company-sponsored speaker’s bureau from AbbVie, Pfizer, Roche, Bristol-Myers, Lilly, Janssen, and MSD and received support for attending meetings and/or travel from AbbVie, Pfizer, Roche, Bristol-Myers, Lilly, Janssen, and MSD. The other co-authors have declared no competing interests., (© The Author(s), 2022.)

Objectives: To determine whether functional vascular endothelial growth factor (VEGF) polymorphisms influence the expression of the clinical phenotype of giant cell arteritis (GCA). We also evaluated whether VEGF polymorphism is associated with the development of severe ischaemic manifestations in patients with GCA regardless of the clinical phenotype, classic cranial GCA or predominantly extracranial GCA large vessel vasculitis (LVV)., Methods: VEGF rs833061 T/C, rs2010963 G/C and rs3025039 C/T polymorphisms were genotyped in 185 patients with biopsy-proven cranial GCA, 105 with extracranial LVV-GCA and 490 healthy controls. Allelic combinations (haplotypes) of VEGF were carried out. Comparisons were performed between patients with GCA and healthy controls as well as between patients with GCA stratified according to the clinical phenotype and the presence of severe ischaemic manifestations., Results: No significant differences in genotype, allele, and haplotype frequencies of VEGF were found between patients with GCA and healthy controls as well as between GCA patients with the classic cranial pattern and the extracranial LVV-GCA pattern of the disease. However, the VEGF CGC haplotype (OR= 1.63 [1.05-2.53]) and the CGT haplotype (OR= 2.55 [1.10-5.91]) were significantly more frequent in GCA patients with severe ischaemic complications compared to those patients without these complications., Conclusions: VEGF haplotypes seem to play a role in the development of severe ischaemic manifestations in GCA patients, regardless of the clinical phenotype of expression of the disease.

Introduction: Sarcopenia is defined by a loss of muscle mass and function associated with mortality, decreased physical performance, falls, and disability. Since chronic inflammation and decreased physical activity are risk factors for developing sarcopenia, it is critical to assess the role of sarcopenia in immune-mediated rheumatic diseases (IMRDs). Moreover, nutritional interventions are emerging as key modifiable and affordable options to improve physical performance in sarcopenia., Objective: The aim of this review is to critically summarize current information on the evidence linking nutritional interventions and sarcopenia in IMRDs., Methods: The search and selection of articles was performed in Medline, Dimensions.ai, Google Scholar, Cochrane Library, Epistemonikos, and Trip Database. The results were clustered into three areas: sarcopenia and IMRDs, sarcopenia and biological disease-modifying antirheumatic drugs (bDMARDs), and nutritional interventions for sarcopenia., Findings: Several cross-sectional studies have shown a higher prevalence of sarcopenia in IMRDs, such as rheumatoid arthritis. Although not fully established, evidence linking sarcopenia and other IMRDs (ankylosing spondylitis and systemic sclerosis) has been also described. For secondary sarcopenia prevention and treatment, bDMARDs' administration proved efficacy in patients with rheumatoid arthritis. Furthermore, there is growing evidence linking nutrition to the prevention and treatment of sarcopenia. Evidence linking unfavourable results in nutritional risk assessment, insufficient intake of protein, vitamin D, antioxidant nutrients, and long-chain polyunsaturated fatty acids and sarcopenia have been reported., Conclusion: Given that sarcopenia and IMRDs have strong links, further research is needed to improve patient care., (© 2021. The Author(s).)

Objectives: To explore current evidence on the management of poor prognostic factors in rheumatoid arthritis (RA) and to investigate whether this evidence is taken into account by clinicians when deciding on treatment in daily clinical practice., Methods: We performed a systematic literature review (SLR) to analyse the effects of currently available biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi) on the classically accepted poor prognostic factors of RA. All randomized controlled trials reporting subgroup analyses about effects on prognostic factors were identified and synthesized. In a second phase, a two-round Delphi survey was carried out to contrast the SLR results with the grade of agreement of a large group of rheumatologists about the effectiveness of each drug class on each prognostic factor., Results: According to the Delphi results, the only prognostic factor that significantly influenced the selection of treatment was the presence of interstitial lung disease (ILD), being the preferred treatment in this scenario abatacept or rituximab. The rest of the poor prognostic factors (including high disease activity at baseline, disability as measured by the Health Assessment Questionnaire index, seropositivity, elevated acute-phase reactants, and evidence of erosions based on plain radiography or ultrasonography) did not seem to significantly influence rheumatologists when choosing a treatment. The results of the SLR results did not show solid evidence regarding the use of any specific therapy in the management of patients with specific poor factors, except in the case of RA-ILD, although the data in the literature in this regard are not free of bias., Conclusions: The only prognostic factor that seems to significantly influence the selection of treatment is the presence of RA-ILD., (Copyright © 2021 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Objective: To assess the efficacy and safety of tocilizumab (TCZ) in Caucasian patients with refractory Takayasu's arteritis (TAK) in clinical practice., Methods: A multicenter study of Caucasian patients with refractory TAK who received TCZ. The outcome variables were remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A comparative study between patients who received TCZ as monotherapy (TCZ MONO ) and combined with conventional disease modifying anti-rheumatic drugs (cDMARDs) (TCZ COMBO ) was performed., Results: The study comprised 54 patients (46 women/8 men) with a median [interquartile range (IQR)] age of 42.0 (32.5-50.5) years. TCZ was started after a median (IQR) of 12.0 (3.0-31.5) months since TAK diagnosis. Remission was achieved in 12/54 (22.2%), 19/49 (38.8%), 23/44 (52.3%), and 27/36 (75%) patients at 1, 3, 6, and 12 months, respectively. The prednisone dose was reduced from 30.0 mg/day (12.5-50.0) to 5.0 (0.0-5.6) mg/day at 12 months. An improvement in imaging findings was reported in 28 (73.7%) patients after a median (IQR) of 9.0 (6.0-14.0) months. Twenty-three (42.6%) patients were on TCZ MONO and 31 (57.4%) on TCZ COMBO : MTX ( n  = 28), cyclosporine A ( n  = 2), azathioprine ( n  = 1). Patients on TCZ COMBO were younger [38.0 (27.0-46.0) versus 45.0 (38.0-57.0)] years; difference (diff) [95% confidence interval (CI) = -7.0 (-17.9, -0.56] with a trend to longer TAK duration [21.0 (6.0-38.0) versus 6.0 (1.0-23.0)] months; diff 95% CI = 15 (-8.9, 35.5), and higher c-reactive protein [2.4 (0.7-5.6) versus 1.3 (0.3-3.3)] mg/dl; diff 95% CI = 1.1 (-0.26, 2.99). Despite these differences, similar outcomes were observed in both groups (log rank p  = 0.862). Relevant adverse events were reported in six (11.1%) patients, but only three developed severe events that required TCZ withdrawal., Conclusion: TCZ in monotherapy, or combined with cDMARDs, is effective and safe in patients with refractory TAK of Caucasian origin., Competing Interests: Conflict of interest statement: Disclosures that might be interpreted as constituting of possible conflict(s) of interest for the study: DP-P is supported by a research contract from the Carlos III Health Institute of Spain (Rio Hortega program, ref. CM20/00006) and has received research support from UCB Pharma, Roche, Sanofi, Pfizer, AbbVie, and Lilly. MAG-G received grants/research supports from Abbvie, MSD, Jansen, and Roche and had consultation fees/participation in company sponsored speaker’s bureau from Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene, and MSD. RB received grants/research supports from Abbvie, MSD, and Roche, and had consultation fees/participation in company sponsored speaker’s bureau from Abbvie, Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma, and MSD. The remaining authors declare they do not have conflict of interest., (© The Author(s), 2021.)

Objectives: Evidence from genome-wide and candidate gene association studies, familial aggregation and linkage analyses demonstrate the genetic contribution to fibromyalgia (FM) disease. This study aimed to identify genetic biomarkers of FM and its related comorbid disorders, by exploring 41 polymorphisms potentially involved in FM pathogenesis in families with at least one patient with FM., Methods: Core symptoms were assessed, and blood samples collected from 556 patients with FM and 395 healthy relatives. For the genetic study, a final sample of 401 FM patients and 232 healthy controls was selected, discarding patients with concomitant pathologies and controls with chronic pain. A family-based approach using DFAM test (Plink) and SNPs (single nucleotide polymorphisms) combination analyses to compare FM patients vs. controls were first applied. Second, the genotypic distribution of subgroups of FM patients, stratified by severe vs. mild symptoms of pain, depression and sleep impairment, was considered., Results: No evidence of associations with FM per se were detected, using either a family-based approach or SNPs combination analyses. However, considering the subgroups of FM patients, the SNP rs6454674 (CNR1, cannabinoid receptor 1 gene) was found as a potential genetic marker of FM correlated with depression (p<.001)., Conclusions: No significant associations using either the family-based analysis or the SNPs combination tests dissociated FM patients and their healthy relatives. FM patients with and without depression showed a significant difference in the genotypic distribution related to the SNP rs6454674 in the cannabinoid receptor 1 gene (CNR1) indicating that FM is not a homogenous disorder.

Objective: To compare the efficacy and safety of TCZ in monotherapy (TCZ MONO ) vs. combined with conventional immunosuppressive drugs (TCZ COMBO ) in Giant Cell Arteritis (GCA) in a clinical practice scenario., Methods: Multicenter study of 134 patients with refractory GCA. Patients on TCZ MONO (n = 82) were compared with those on TCZ COMBO (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 TCZ COMBO 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 TCZ COMBO , the improvement was similar in both groups at 12 months. Moreover, in the TCZ COMBO 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., Competing Interests: Declaration of Competing Interest Disclosures that might be interpreted as constituting possible conflict(s) of interest for the study: Dr. Mónica Calderón-Goercke attendance at conferences Lilly, Abbvie, and Pfizer. Dr. S. Castañeda is assistant professor, cátedra EPID-Future, funded by UAM-Roche, Universidad Autónoma de Madrid (UAM). Dr. Vicente Aldasoro had consultation fees/participation in company-sponsored speaker´s bureau from Janssen, BMS, MSD, Roche, Sanofi, Pfizer, Novartis, Amgen, Lilly, Abbvie, Gebro, Nordic, Lacer, Alter, UCB, ASAC Pharma, Menarini and Celgene. Dr. Eva Pérez-Pampín had consultation fees/participation in company-sponsored speaker´s bureau from MSD, BMS, Janssen, Abbvie, Novartis, Pfizer, Roche, UCB, Lilly, Celgene, and Nordic. Dr. Francisca Sivera received grants from Roche. Dr. Eugenio De Miguel had consultation fees/participation in company-sponsored speaker´s bureau from Abbvie, Novartis, Pfizer, BMS, MSD, UCB, Roche, Grünenthal and Janssen. Dr. Diana Prieto-Peña attendance at conferences Lilly, Roche, and Pfizer. Prof. José L. Hernández received grants from Amgen and had participation in company-sponsored speaker´s bureau from Amgen, MSD, Bayer, and Esteve. Dr. MA Gonzalez-Gay received grants/research supports from Abbvie, MSD, and Roche, and had consultation fees/participation in company-sponsored speaker´s bureau from Pfizer, Celgene, Novartis, Roche, Sanofi, and Lilly. Dr. R Blanco received grants/research supports from Abbvie, MSD, and Roche, and had consultation fees/participation in company-sponsored speaker´s bureau from Abbvie, Pfizer, Roche, BMS, Janssen, and MSD. No financial disclosures declared: Ignacio Villa, Clara Moriano, Susana Romero-Yuste, Javier Narváez, Catalina Gómez-Arango, Rafael Melero, Elena Becerra-Fernández, Marcelino Revenga, Noelia Álvarez-Rivas, and Carles Galisteo., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To determine if patients with the predominant extracranial large-vessel-vasculitis (LVV) pattern of giant cell arteritis (GCA) have a distinctive HLA-B association, different from that reported in biopsy-proven cranial GCA patients. In a further step we assessed if the combination of HLA-B and HLA-DRB1 alleles confers an increased risk for GCA susceptibility, either for the cranial and extracranial LVV phenotypes., Methods: A total of 184 patients with biopsy-proven cranial GCA, 105 with LVV-GCA and 486 healthy controls were included in our study. We compared HLA-B phenotype frequencies between the three groups., Results: HLA-B*15 phenotype was significantly increased in patients with classic cranial GCA compared to controls (14.7% versus 5.8%, respectively; p<0.01; OR [95% CI] =2.81 [1.54-5.11]). It was mainly due to the HLA-B*15:01 allele (12.5% versus 4.0%, respectively; p<0.01; OR [95% CI] =3.51 [1.77-6.99]) and remained statistically significant after Bonferroni correction. Similar HLA-B*15 association was observed in patients with the LVV-GCA (11.4% versus 5.8%, p=0.04, OR [95% CI] =2.11 [1.04-4.30]). This association was also mainly due to the HLA-B*15:01 allele (10.5% versus 4.0%, respectively; p=0.0054; OR [95% CI] =2.88 [1.19-6.59]). Noteworthy, the presence of HLA-B*15:01 together with HLA-DRB1*04:01 led to an increased risk of developing both cranial and extracranial LVV-GCA., Conclusions: Susceptibility to GCA is strongly related to the HLA region, regardless of the clinical phenotype of expression of the disease.

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 < 0.001) and a CS-sparing effect from a median 7.5 (5-10) to 5 (2.5-7.5) mg/day at the end of follow-up (P < 0.001) was also observed. ABA was withdrawn in 62 (23.6%) patients due to adverse events (n = 30), articular inefficacy (n = 27), ILD worsening (n = 3) and other causes (n = 2)., Conclusion: ABA may be an effective and safe treatment for patients with RA-ILD., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To determine whether giant cell arteritis (GCA) patients with the typical pattern of cranial ischemic manifestations and those with the extracranial large-vessel-vasculitis (LVV)-GCA phenotype exhibit different HLA-DRB1 association., Methods: 178 biopsy-proven GCA patients who had cranial ischemic features but no LVV manifestations, 100 patients with LVV-GCA without cranial ischemic manifestations and 486 ethnically matched healthy controls were recruited. All patients and controls were Spanish of European ancestry. We compared HLA-DRB1 phenotype frequencies between the three groups., Results: Both GCA subgroups had well-differentiated clinical features. Patients with LVV-GCA were younger (68.0 ± 10.0 years versus 74.0 ± 10.4 years; p < 0.01) and presented more commonly with polymyalgia rheumatica symptoms (81% versus 39.3%; p < 0.01) than those with the classic cranial GCA phenotype. HLA-DRB1*04 phenotype frequency was significantly increased in patients with classic cranial GCA compared to controls (42.1% versus 23.5%, respectively; p < 0.01; odds ratio-OR [95% confidence interval-CI] = 2.38 [1.62-3.47]). This association was mainly due to the HLA-DRB1*04:01 allele (20.8% versus 5.3%, respectively; p < 0.01; OR [95% CI] = 4.64 [2.63-8.26]). HLA-DRB1*04 association was also observed in LVV-GCA patients when compared to controls (46.0% versus 23.5%, respectively; p < 0.01; OR [95% CI] = 2.78 [1.73-4.44]). Similar to cranial GCA, the association was also mainly due to the HLA-DRB1*04:01 allele (19.0% versus 5.3%, respectively; p < 0.01; OR [95% CI] = 4.15 [2.06-8.19]). Cranial and LVV-GCA patients did not exhibit HLA-DRB1 allele differences., Conclusion: Cranial and extracranial LVV-GCA share similar HLA-DRB1 association., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: 1) To systematically and critically review the evidence of combined therapy with synthetic disease-modifying antirheumatic drugs (DMARD) in rheumatoid arthritis (RA); 2) To design practical recommendations on their use., Methods: A systematic literature review (SLR) was performed with a sensitive bibliographic search strategy in Medline, EMBASE and Cochrane Library. We selected randomized clinical trials that analyzed the efficacy and/or safety of 1) combined therapy of synthetic compared with sequential therapy of synthetic DMARD in early RA; and 2) combination of methotrexate+leflunomide or triple therapy with synthetic DMARD in established RA refractory to synthetic DMARD. Two reviewers made the first selection by title and abstract and 11 performed the selection after detailed review of the articles and data collection. The quality of the studies was evaluated with the Jadad scale. Based on the results, related recommendations were agreed upon in a nominal group meeting., Results: Ultimately, no articles were included in the SLR. The analysis of the reviewed articles demonstrated the effectiveness of the treatment with synthetic DMARD following a "treat to target" strategy in early RA patients, and of combination therapy of synthetic DMARD in established RA refractory to synthetic DMARD. This resulted in 6 recommendations concerning combination therapy with synthetic DMARD., Conclusions: These recommendations aim to facilitate decision-making with the use of combined therapy with DMARD in RA., (Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Objectives: The objective of the present study was to assess the efficacy of apremilast (APR) in the management of refractory oral and/or genital ulcers in patients with Behçet's disease (BD)., Methods: National multicentre open-label observational study on BD patients with recurrent oral and/or genital ulcers. In all cases orogenital ulcers were refractory to conventional therapy. APR was given and maintained at standard dose of 30 mg twice daily. The main outcome was the achievement of oral and/or genital ulcers remission. Efficacy of APR for other clinical manifestations was also evaluated., Results: We included 51 patients (35 women/16 men; mean age 44.7±13.2 years). Before APR, all patients had received several systemic conventional and/or biologic drugs. APR was initiated because of refractory oral (n=19) or genital (n=2) aphthous ulcers or both (n=30). Other manifestations found at APR onset were arthralgia/arthritis (n=16), folliculitis/pseudofolliculitis (n=14), erythema nodosum (n=3), furunculosis (n=2), paradoxical psoriasis induced by TNF-α-inhibitors (n=2), ileitis (n=2), deep venous thrombosis (n=2), leg ulcers (n=1), erythematosus and scaly skin lesions (n=1), fever (n=1), unilateral anterior uveitis (n=1) and neuro Behçet (n=1). After a mean follow-up of 8.5±6.9 months, most patients had experienced improvement of orogenital ulcers and prednisone dose had been successfully reduced or discontinued. APR also yielded improvement of some non-aphthous manifestations such as the cutaneous follicular and intestinal manifestations. However, the effect on musculoskeletal manifestations was variable., Conclusions: APR yielded a rapid and maintained improvement of refractory mucocutaneous ulcers of BD, even in patients refractory to several systemic drugs including biologic therapy.

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'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 μm vs. 183.4 ± 139.5 μm; p = 0.02), mean ± SD MT (270.7 ± 23.2 μm vs. 369.6 ± 137.4 μm; p = 0.03). Besides, the median (IQR) prednisone-dose was also reduced from 40 (10-61.5) mg/day at baseline to. 2.5 (0-5) 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.

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

Objective: Tocilizumab (TCZ) has shown efficacy in clinical trials on giant cell arteritis (GCA). Real-world data are scarce. Our objective was to assess efficacy and safety of TCZ in unselected patients with GCA in clinical practice Methods: Observational, open-label multicenter study from 40 national referral centers of GCA patients treated with TCZ due to inefficacy or adverse events of previous therapy. Outcomes variables were improvement of clinical features, acute phase reactants, glucocorticoid-sparing effect, prolonged remission and relapses. A comparative study was performed: (a) TCZ route (SC vs. IV); (b) GCA duration (≤6 vs. >6 months); (c) serious infections (with or without); (d) ≤15 vs. >15 mg/day at TCZ onset., Results: 134 patients; mean age, 73.0 ± 8.8 years. TCZ was started after a median [IQR] time from GCA diagnosis of 13.5 [5.0-33.5] months. Ninety-eight (73.1%) patients had received immunosuppressive agents. After 1 month of TCZ 93.9% experienced clinical improvement. Reduction of CRP from 1.7 [0.4-3.2] to 0.11 [0.05-0.5] mg/dL (p < 0.0001), ESR from 33 [14.5-61] to 6 [2-12] mm/1st hour (p < 0.0001) and decrease in patients with anemia from 16.4% to 3.8% (p < 0.0001) were observed. Regardless of administration route or disease duration, clinical improvement leading to remission at 6, 12, 18, 24 months was observed in 55.5%, 70.4%, 69.2% and 90% of patients. Most relevant adverse side-effect was serious infections (10.6/100 patients-year), associated with higher doses of prednisone during the first three months of therapy., Conclusion: In clinical practice, TCZ yields a rapid and maintained improvement of refractory GCA. Serious infections appear to be higher than in clinical trials., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The aim of the study is to benchmark the use and attributed importance of well-established prognostic factors in rheumatoid arthritis (RA) in daily clinical practice, and to contrast the use of factors with their ability to predict outcome. Medline was searched (inception-Sep. 2016) for systematic reviews on factors predicting death, disability, structural damage or remission in RA. All factors identified were compiled in a matrix of factors × outcomes, and scoping reviews for each cell were then performed. A survey to 42 rheumatologists randomly selected explored the use of the list of prognostic factors and inquired about the perceived strength of association with poor prognosis. In a second round, participants were exposed to evidence from the matrix and to responses from other participants. Change on perceived strength of association was evaluated. Rheumatologists report using prognostic factors in clinical practice on a daily basis. Very young onset, joint counts at diagnosis, rheumatoid factor, ACPA, and radiographic erosions are used frequently and correctly recognized as strong predictors. Comorbidities and other associated problems, such as obesity, low bone mineral density, cardiovascular disease, or extra-articular manifestations, are perceived as moderately associated to prognosis but, nevertheless, rheumatologists also use them profusely. Genetic and other biomarkers and osteitis by magnetic resonance are less accessible in daily practice and they obtained better results on second round (probably after knowing the strength of association with prognosis). Rheumatologists use widely most prognostic factors with a strong predictive value. However, factors with low evidence of prognostic value are also used and some factors are not used despite good evidence.

Objective: Interstitial lung disease (ILD) is one of the most serious complications of rheumatoid arthritis (RA). In the present study, we aimed to assess the efficacy of abatacept (ABA) in patients with ILD associated to RA., Methods: National multicenter, non-controlled, open-label registry study of RA patients with ILD treated with ABA., Results: 63 patients (36 women) with RA-associated ILD undergoing ABA therapy were studied. The mean ± standard deviation age at the time of the study was 63.2 ± 9.8 years. The median duration of RA and ILD from diagnosis were 6.8 and 1 year, respectively. RA was seropositive in 55 patients (87.3%). In 15 (23.8%) of 63 patients the development of ILD was closely related to the administration of synthetic or biologic disease modifying anti-rheumatic drugs. After a follow-up of 9.4 ± 3.2 months, two-thirds of patients remained stable whereas one-quarter experienced improvement in the Modified Medical Research Council scale. At that time forced vital capacity remained stable in almost two-thirds of patents and improved in one out of five patients assessed. Also, diffusing capacity of the lung for carbon monoxide remained stable in almost two-thirds and showed improvement in a quarter of the patients assessed. At 12 months, 50% of the 22 patients in whom chest HRCT scan was performed due persistence of respiratory symptoms showed stabilization, 8 (36.4%) improvement and 3 worsening of the HRCT scan pattern. Eleven of 63 patients had to discontinue ABA, mainly due to adverse events., Conclusion: ABA appears to be an effective in RA-associated ILD., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A standard model of the Patient Information Sheet (PIS) and Informed Consent (IC) would facilitate compliance with the guaranteed rights of the patient when their health data is used in any form for purposes other than medical assistance, like the release of case reports and case series. This model would be suitable for the presentation of case reports in a congress in any form (verbal communication, poster or presentation), for its publication in a journal that does not require the completion of its own model, or even for teaching practice. A standard model of the PIS and IC would facilitate the application of the current regulations and good clinical practices in clinical research: it would guarantee the compliance of the professionals' duty of protection of the patient's privacy against the use of their health data for purposes other than medical assistance., (Copyright © 2018. Publicado por Elsevier España, S.L.U.)

(1) To assess the degree of convergence between the 1990 and 2010 American College of Rheumatology (ACR) diagnostic criteria; (2) To evaluate the validity and reliability of the 2010 ACR criteria; (3) To validate the Spanish version of the Fibromyalgia Survey Questionnaire (FSQ); and (4) To assess the utility of the FSQ to differentiate fibromyalgia (FM) subgroups by disease severity. In the first study, agreement between the 1990 and 2010 ACR criteria for FM diagnosis was analyzed in a sample of 80 FM patients and 59 healthy controls. Algometry (mean threshold and tender points count) and the 2010 ACR indices [Symptom Severity Scale (SSS), Widespread Index (WPI) and Polysymptomatic Distress Scale (PSD)] were correlated with the key symptoms of FM and with indices of disease interference and quality of life. In a second study, we evaluated the validity and internal consistency of the Spanish version of the FSQ, as well as its ability to discriminate between groups of FM patients with low and high symptom severity. There is good agreement between the 1990 and 2010 ACR criteria for FM diagnosis. The 2010 ACR indices (SSS, WPI and PSD) demonstrated very adequate construct validity and appeared to be useful in the assessment of disease severity and global impact of FM. The FSQ had good internal consistency and validity and showed 100 % concordance with 2010 ACR criteria applied by a clinician. In addition, the FSQ proved to be useful in differentiating FM severity subgroups.

The CD4(+) T-cell reduction characteristic of human immunodeficiency virus type 1 (HIV-1) infection is thought to result, in addition to infected T-cell death, mainly from uninfected bystander T-cell apoptosis. Nevertheless, the immunological and virological mechanisms leading to T-cell death during HIV-1 infection are not yet fully understood. In the present study, we analysed the individual implication of the p38 mitogen-activated protein kinase (MAPK) isoforms (p38alpha, p38beta, p38gamma and p38delta) during apoptosis induced by HIV-1, taking into account that HIV-1 replication is known to be blocked by p38 inhibitors. For this purpose, we used the SupT1 cell line, where death induced by HIV-1 mainly occurs by uninfected bystander cell apoptosis. A variety of SupT1-based cell lines were constructed constitutively expressing, under the control of cytomegalovirus promoter (PCMV), each dominant-negative (dn) p38 isoform and each wild-type p38 isoform as a control. An enhanced green fluorescent protein marker gene, under the control of the HIV-1 promoter, was inserted in all of them. These cell lines were infected with HIV-1 and analysed by flow cytometry. We found that survival in SupT1-based cell lines infected by HIV-1 was increased by the p38alphadn, p38gammadn and p38deltadn isoforms, but not by the p38betadn isoform. HIV-1 replication was delayed most by p38deltadn and to a lesser extent by p38alphadn and p38gammadn. Moreover, these three isoforms, p38alphadn, p38gammadn and p38deltadn, reduced apoptosis induced by HIV-1. These results suggest that, in SupT1-based cell lines, p38alpha, p38gamma and p38delta, but not p38beta, are implicated in both HIV-1 induced replication and apoptosis in infected and uninfected bystander cells.

The role played by different humoral factors, including antiphospholipid antibodies, in the pathogenesis of Tourette syndrome (TS) is still presently unclear. We present a patient with chronic and severe TS who, at the age of 16 years, presented an ischemic stroke in the left posterior cerebral artery and/or postero-inferior temporal branch of the left medial cerebral artery. A complete study was negative with the exception of a positive lupus anticoagulant. The stroke was related with the primary antiphospholipid syndrome (APS). The stroke manifested visual abnormalities and thereafter by secondary generalized complex partial seizures. The epileptic syndrome was initially difficult to control but responded dramatically to levetiracetam. With this therapy, the manifestations of TS, especially the tics, improved. We conclude that some TS cases may present APS. In addition, levetiracetam may be useful in the management of TS. Further investigations should pursue both these facts.

Objective: The aim of this study is to assess a real-time PCR technique on the LightCycler 2.0 with SYBR-Green I detection as compared to another real-time PCR method based on detection with FRET (fluorescence resonance energy transfer) probes for the quantification of CMV DNA., Methods: The two real-time PCR methods were used to test plasma samples from immunocompromised patients with clinically suspected CMV disease, patients under follow-up without symptoms, and healthy adults. A standard curve for quantitative analysis by the SYBR-Green I method was performed with 10-fold diluted solutions of DNA from the CMV Towne strain (ATCC VR-977) cultured in MRC-5 monolayer. In addition, frozen samples from patients positive for CMV pp65 antigenemia were also analyzed and results compared using the two real time PCR methods., Results: The real-time PCR technique using SYBR-Green I on the LightCycler 2.0 was a highly specific, fast, simple and reliable test to quantify CMV; moreover, it was cost-effective., Conclusion: Quantification of CMV DNA in plasma using this sensitive, fast, low-cost method was advantageous for the diagnosis and follow up of patients with opportunistic CMV infection, which are increasingly more frequent in our daily hospital clinical practice.

Viral hepatitis is an infectious disease affecting the liver. At this time, five different human hepatitis viruses are recognized and characterized in detail: Hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). The hepatitis viruses differ widely in their modes of transmission and clinical features. Whereas all of them can cause acute hepatitis, only HBV, HDV, and HCV cause chronic hepatitis. This article reviews the epidemiology and clinical manifestations of the different types of viral hepatitis.