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Backgroud: Juvenile idiopathic arthritis (JIA) treatment is aimed at inducing remission to prevent joint destruction and disability. However, it is unclear what is the long-term impact on health-related outcomes of the timing of biological disease-modifying anti-rheumatic drug (bDMARD) initiation in JIA. Our aim was to evaluate the long-term impact of the time between JIA onset and the initiation of a bDMARD in achieving clinical remission, on physical disability and health-related quality of life (HRQoL). Methods: Adult JIA patients registered in the Rheumatic Diseases Portuguese Register (Reuma.pt) and ever treated with bDMARD were included. Data regarding socio-demographic, JIA-related characteristics, disease activity, physical disability (HAQ-DI), HRQoL (SF-36) and treatments were collected at the last visit. Patients were divided into 3 groups (£ 2 years, 2-5 years, or > 5 years), according to the time from disease onset to bDMARD initiation. Regression models were obtained considering remission on/off medication, HAQ-DI, SF-36 and joint surgeries as outcomes and time from disease onset to bDMARD start as an independent variable. Results: 361 adult JIA patients were evaluated, with a median disease duration of 20.3 [IQR 12.1; 30.2] years. 40.4% had active disease, 35.1% were in remission on medication and 24.4% in drug-free remission; 71% reported some degree of physical disability. Starting a bDMARD > 5 years after disease onset decreased the chance of achieving remission off medication (OR 0.24; 95% CI 0.06, 0.92; p= 0.038). Patients who started a bDMARD after 5 years of disease onset had a higher HAQ and worse scores in the physical component, vitality and social function domains of SF-36, and more joint surgeries when compared to an earlier start. Conclusion: Later initiation of bDMARDs in JIA is associated with greater physical disability, worse HRQoL and lower chance of drug-free remission in adulthood.

Coronavirus Disease 2019 (COVID-19) generally appears to have milder clinical symptoms and fewer laboratory abnormalities in children. It remains unknown whether children and young people with inflammatory chronic diseases who acquire SARS-CoV-2 infection have a more severe course, due to either underlying disease or immunosuppressive treatments.To assess the epidemiological features and clinical outcomes of children and young people with inflammatory chronic diseases followed at Pediatric Rheumatology Clinics who were infected with SARS-CoV-2.A multicentric prospective observational study was performed. Data on demographic variables, clinical features and treatment were collected between March 2020 and September 2021, using the Rheumatic Diseases Portuguese Register (Reuma.pt) and complemented with data from the hospital clinical records.Thirty-four patients were included, 62% were female, with a median age of 13 [8-16] years and a median time of inflammatory chronic disease of 6 [3-10] years. The most common diagnoses were juvenile idiopathic arthritis (n=22, 64.7%), juvenile dermatomyositis (n=3, 8.8%) and idiopathic uveitis (n=3, 8.8%). Twenty patients were on conventional synthetic disease modifying drugs (csDMARDs) and 10 on biologic DMARDs (bDMARDs). Five patients had an active inflammatory disease at the time of infection (low activity). Seven patients had an asymptomatic infection while 27 patients (79%) had symptoms: cough (n=12), fever (n=11), rhinorrhea (n=10), headache (n=8), malaise (n=8), fatigue (n=7), anosmia (n=5), myalgia (n=5),dysgeusia (n=4), odynophagia (n=4), chest pain (n=2), diarrhea (n=2), arthralgia (n=1), vomiting (n=1) and conjunctivitis (n=1). No patient required hospitalization or directed treatment, and all recovered without sequelae. In 8 patients there was a change in the baseline medication during the infection: suspension of bDMARDs (n=4), reduction of bDMARDs (n=1), suspension of csDMARDs (n=4) and reduction of csDMARDs (n=2). Only in one patient with juvenile dermatomyositis (who discontinued bDMARDs and csDMARDs), the underlying disease worsened.This is the first study involving children with inflammatory chronic diseases followed at Rheumatology Clinics and SARS-CoV-2 infection in Portugal. In our cohort, mild illness was predominant, which is consistent with the literature. There was no need for hospitalization or specific treatment, and, in most cases, no worsening of the underlying disease was identified.

Clinically amyopathic dermatomyositis (CADM) is a rare condition characterized by dermatomyositis skin lesions without clinically apparent muscle involvement. Respiratory involvement is common, occurring in about half of the cases. Spontaneous pneumomediastinum (PnM) is a rare, and often fatal, complication of CADM. We report a case of a 61-year-old female patient who was diagnosed with anti-melanoma differentiation- associated gene 5 antibody-associated CADM and interstitial lung disease. She developed an extensive spontaneous PnM with subcutaneous emphysema. The patient was treated with a conservative approach which was, initially, successful in reducing the size of the PnM. However, the patient died from an eventual nosocomial pneumonia requiring mechanical ventilation. This case illustrates that improving the management of CADM associated PnM, remains a major unmet need.

To identify predictive factors of relapse after discontinuation of Methotrexate (MTX) in Juvenile Idiopathic Arthritis (JIA) patients with inactive disease.We conducted a prospective multicenter cohort study of patients diagnosed with JIA using real world data from the Portuguese national register database, Reuma.pt. Patients with JIA who have reached JADAS27 inactive disease and discontinued MTX before the age of 18 were evaluated.A total of 1470 patients with JIA were registered in Reuma.pt. Of the 119 bionaive patients who discontinued MTX due to inactive disease, 32.8% have relapsed. Median time of persistence (using the Kaplan-Meier method and log-rank tests) with inactive disease was significantly higher in patients with more than two years of remission before MTX discontinuation and in those who did not use NSAIDs at time of MTX discontinuation. In Cox regression analyses and after adjustment for age at diagnosis, MTX tapering and JIA category, the use of NSAIDs at the time of MTX discontinuation (HR, 1.98 95%CI 1.03-3.82) and remission time of less than two years before suspension (HR, 3.12 95%CI 1.35-7.13) remained associated with relapse. No association was found between JIA category or the regimen of MTX discontinuation and the risk of relapse.In this large cohort we found that the use of NSAIDs at the time of MTX discontinuation was associated with a two times higher likelihood of relapse. In addition, longer duration of remission before MTX withdrawal reduces the chance of relapse in bionaive JIA patients.

Cat scratch disease (CSD) is a zoonosis caused by Bartonella henselae, which is usually transmitted to humans through scratches or bites from infected cats. It is primarily a disease of children and adolescents, although it can affect individuals of any age. In approximately 10% of cases, patients can present atypical manifestations that may involve the musculoskeletal system. Herein, we report a case of a healthy 51-year-old man that developed low-grade fever and regional lymphadenopathy, followed by erythema nodosum and oligoarthritis. He had been scratched and bitten by his cat before the onset of symptoms. The diagnosis was confirmed serologically by the presence of high titers of specific IgG antibodies. Bartonella henselae was also detected in the blood of the owner's cat by PCR and DNA sequencing.

Dissertação de Mestrado Integrado em Medicina Veterinária O desenvolvimento e disseminação de microrganismos resistentes a antimicrobianos causados pelo uso inadequado desses compostos é uma grande preocupação de saúde pública, pressionando para o desenvolvimento de novas estratégias terapêuticas. A otite externa (OE) é uma das doenças dermatológicas mais comumente diagnosticadas em cães, tendo uma etiologia multifatorial. Entre os agentes bacterianos mais frequentemente associados à OE canina, Pseudomonas aeruginosa é de especial preocupação, devido ao seu frequente perfil de multirresistências e notável capacidade de formar biofilmes, estruturas que tornam os tratamentos desafiadores e propiciam para a cronicidade e recorrência das infeções. O aumento da prevalência de resistência antimicrobiana entre bactérias em cães com OE leva à necessidade de se encontrar novos agentes terapêuticos, incluindo o uso de óleos essenciais ou géis contendo péptidos antimicrobianos, como o Peptivet®. O objetivo principal deste estudo foi comparar a eficácia de diferentes antimicrobianos no controlo da OE canina de P. aeruginosa, incluindo Gentamicina, um antibiótico convencional, e Peptivet® e Óleo Essencial de Lavanda (OEL), duas estratégias antimicrobianas inovadoras. O outro objetivo foi avaliar o impacto do cerúmen canino na atividade inibitória do Peptivet® com o objetivo de avaliar se esta é mantida em condições que melhor mimetizem as OE in vivo, dado que o cerúmen e o conteúdo lipídico, que estão alterados na OE, podem influenciar a penetração e ação de compostos antimicrobianos. Dos antimicrobianos avaliados, o OEL apresentou a maior eficácia após 30 minutos de incubação, demonstrando capacidade de inibir e erradicar os biofilmes formados por 61,5% dos isolados em estudo, e a Gentamicina apresentou a maior eficácia após 24 horas de incubação, demonstrando capacidade para inibir e erradicar biofilmes formados por 100% dos isolados em estudo. O Peptivet® apresentou a menor eficácia, tendo sido aproximadamente metade da eficácia do OEL após 30 minutos de incubação. Os resultados deste estudo indicam que o Óleo Essencial de Lavanda avaliado pode ser considerado uma alternativa inovadora com grande potencial para o tratamento e prevenção da OE causada por P. aeruginosa em cães, sugerindo a necessidade de continuar esta linha de investigação com o objetivo da sua utilização futura em contexto clínico. ABSTRACT - In vitro evaluation of innovative antimicrobial approaches aiming at controlling otitis by Pseudomonas aeruginosa in dogs - The development and spread of antimicrobial resistant microorganisms caused by the inappropriate use of these compounds is a major public health concern, pressing for the development of new therapeutic strategies. Otitis externa (OE) is one of the most commonly diagnosed dermatological diseases in dogs, having a multifactorial etiology. Among the most frequent bacterial agents associated with canine OE, Pseudomonas aeruginosa is of special concern, due to its frequent multidrug resistance profile and its remarkable ability to form biofilms, structures that make treatments challenging and predispose to the chronicity and recurrence of infections. The increasing prevalence of antimicrobial resistance among bacteria in dogs with OE leads to the need to find new therapeutic agents including the use of Essential Oils or gels containing antimicrobial peptides, such as Peptivet®. The main objective of this study was to compare the antimicrobial potential of different antimicrobials to control P. aeruginosa canine OE, including Gentamicin, a conventional antibiotic, and Peptivet® and Lavanda Essential Oil (OEL), two innovative antimicrobial strategies. The other objective was to assess the impact of canine cerumen on the inhibitory activity of Peptivet®, aiming at evaluating if its inhibitory potential is maintained in conditions which better mimic the ears in vivo environment, since the skin cerumen and lipid content, which are altered in ears with otitis, may influence the penetration and action of antimicrobial compounds. Of the antimicrobials evaluated, the ones that showed the best effectiveness were Lavender Essential Oil after 30 minutes incubation, which demonstrated the ability to inhibit and eradicate the biofilms formed by 61.5% of the isolates under study, and Gentamicin after 24 hours incubation, which demonstrated the ability to inhibit and eradicate biofilms formed by 100% of the isolates under study. Peptivet® had the lowest effectiveness, having approximately half the effectiveness of the oil after 30 minutes of incubation. The results of this study indicate that the evaluated Lavender Essential Oil can be considered an innovative alternative with great potential for the treatment and prevention of external otitis caused by P. aeruginosa in dogs, suggesting the need to continue this line of research in terms of its future use in a clinical context. N/A

ObjectiveTo compare physical disability, mental health, fatigue and health-related quality of life (HRQoL) across juvenile idiopathic arthritis (JIA) categories in adulthood and between JIA and adult-onset rheumatic diseases.MethodsCross-sectional analysis nested in a cohort of adult patients with JIA registered in the Rheumatic Diseases Portuguese Register (Reuma.pt). Physical disability (Health Assessment Questionnaire—Disability Index), mental health symptoms (Hospital Anxiety and Depression Scale), fatigue (Functional Assessment of Chronic Illness Therapy—Fatigue Scale (FACIT-F)) and HRQoL (EuroQol-5D (EQ5D) and Short Form (SF-36)) were compared across JIA categories. Patients with polyarticular JIA and enthesis-related arthritis (ERA) JIA were compared respectively to patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA), matched for gender and age, adjusted for disease duration and activity.Results585 adult patients with JIA were included. Comparison across JIA categories showed that persistent oligoarthritis and patients with ERA reported a higher score in EQ5D and SF-36 physical component when compared with other JIA categories.Polyarticular JIA reported less disability and fatigue than patients with RA (median Health Assessment Questionnaire of 0.25 vs 0.63; pConclusionPersistent oligoarticular JIA and ERA are the JIA categories in adulthood with better HRQoL. Overall, adult polyarticular and patients with ERA JIA have lower functional impairment and better quality-of-life than patients with RA and SpA.

Funding Information: We thank Cláudia Andrade for technical support and Juliana Gonçalves for testing samples for SARS-CoV-2 exposure. We are extremely grateful to all the participants of the study and to the whole rheumatology department at Hospital Egas Moniz that made this study possible. This work was supported by Fundação para a Ciência e Tecnologia (FCT) PTDC/MEC-REU/29520/2017, by iNOVA4Health UID/Multi/04462 and by Portuguese Society for Rheumatology (SPR) grants to H.S. H.S. is supported by FCT through IF/01722/2013 and CEECIND/01049/2020, DAS and RCT were supported by FCT through PD/BD/137409/2018 and UID/Multi/04462, respectively. Publisher Copyright: © 2021, The Author(s). CD4+ T cells mediate rheumatoid arthritis (RA) pathogenesis through both antibody-dependent and independent mechanisms. It remains unclear how synovial microenvironment impinges on CD4+ T cells pathogenic functions. Here, we identified a TLR4+ follicular helper T (Tfh) cell-like population present in the blood and expanded in synovial fluid. TLR4+ T cells possess a two-pronged pathogenic activity whereby direct TLR4+ engagement by endogenous ligands in the arthritic joint reprograms them from an IL-21 response, known to sponsor antibody production towards an IL-17 inflammatory program recognized to fuel tissue damage. Ex vivo, synovial fluid TLR4+ T cells produced IL-17, but not IL-21. Blocking TLR4 signaling with a specific inhibitor impaired IL-17 production in response to synovial fluid recognition. Mechanistically, we unveiled that T-cell HLA-DR regulates their TLR4 expression. TLR4+ T cells appear to uniquely reconcile an ability to promote systemic antibody production with a local synovial driven tissue damage program. publishersversion published

Objective. The aim of this study was to evaluate the self-reported impact of mandatory confinement occurring in the first wave of the SARS-CoV-2 pandemic in Portuguese patients with rheumatoid arthritis (RA), as a means to improve care during this and in future pandemics. Material and methods. The web-based survey COVIDRA was developed to assess 5 domains including RA symptoms, attitudes towards medication, employment status, physical exercise and mental health. The questionnaire was sent to RA patients through e-mail and social media of the Portuguese Society of Rheumatology and two patient associations; and it was filled locally at two rheumatology centers in Lisbon. Recruitment took place during June and July 2020. Results. We obtained 441 valid questionnaires. Most respondents were female (88.4%), caucasian (93.6%) with a mean age of 58 years. The majority had disease lasting >10 years and were treated with csDMARDs (63.2%) and/or bDMARDs/tsDMARDS (23.7%). Over 40% experienced symptom worsening during confinement, almost half considered moderate or severe. Mobility restriction and increased stress, anxiety or depression were responsible for this worsening. Only 2.5% reduced or withheld their immunosuppressive medication due to fear of becoming infected with SARS-CoV-2. After confinement, 16.2% of those previously employed were in a lay-off regime and 3% lost their jobs. Most employed RA patients practiced telework during confinement. The majority of patients decreased or did not practice any physical exercise (80.5%). Symptoms of anxiety and depression developed or worsened in 67.3% and 51.9% respectively, approximately one third were considered moderate or severe. Conclusions. Portuguese RA patients experienced significant symptom worsening, anxiety and depression during the first wave confinement. Only a minority changed their immunosuppressive treatment for fear of SARS-CoV-2 infection. Published literature on these matters shows results very similar to ours.

CD4+ T cells mediate rheumatoid arthritis (RA) pathogenesis through both antibody-dependent and independent mechanisms. It remains unclear how synovial microenvironment impinges on CD4+ T cells pathogenic functions. Here, we identified a TLR4+ follicular helper T (Tfh) cell-like population present in the blood and expanded in synovial fluid. Mechanistically, we unveiled that homotypic T-T cell interactions through non-cognate HLA-DR:TCR contacts regulate TLR4 expression on T cells. TLR4+ T cells possess a two-pronged pathogenic activity. Upon TCR and ICOS engagement, TLR4+ T cells produce IL-21, a cytokine known to sponsor antibody production. However, direct TLR4+ engagement on T cells, by endogenous ligands in the arthritic joint, reprograms them towards an IL-17 inflammatory profile compatible with tissue damage program. Blocking TLR4 signaling with a specific inhibitor impaired IL-17 production in response to synovial fluid recognition. Ex vivo, synovial fluid TLR4+ T cells produced IL-17, but not IL-21. TLR4+ T cells appear to uniquely reconcile an ability to promote systemic antibody production with a local synovial driven tissue damage program. TLR4+ T cells could constitute an attractive cellular target and predictive biomarker for erosive arthritis.

Coronavirus disease 2019 (COVID-19) was reported in Europe in the beginning of February 2020. Typical symptoms included fever, cough and dyspnea, and not much was known about the clinical evolution of the disease. Herein, we report a case of a late complication of COVID-19 infection in a 41-year-old female. The patient presented with a 4-day history of myalgia, low fever, rhinorrhea and loss of smell. COVID-19 was confirmed by real-time polymerase chain reaction (PCR). The patient recovered with conservative treatment, and PCR for COVID-19 turned negative after 5 weeks. However, at 4 weeks after the beginning of the viral symptoms, the patient developed severe arthralgia of some interphalangeal joints of the hands, that lasted for 4 weeks. Laboratory workup revealed no significant changes, and the symptoms resolved with a short course of oral steroids. Reactive viral arthritis might be a late complication of COVID-19.

OBJECTIVE: To investigate the relationship between body mass index (BMI) and disease activity in patients with Juvenile Idiopathic Arthritis (JIA). METHODS: Patients with JIA, aged ≤18 years, registered at the Rheumatic Diseases Portuguese Register (Reuma.pt) in Portugal and Brazil were included. Age- and sex-specific BMI percentiles were calculated based on WHO growth standard charts and categorized into underweight (P 97). Disease activity was assessed by Juvenile Arthritis Disease Activity Score (JADAS-27). Uni- and multivariate analyses were performed. RESULTS: A total of 275 patients were included. The prevalence of underweight, normal weight, overweight and obesity was 6.9%, 67.3%, 15.3% and 10.5%, respectively. Underweight patients had significantly higher number of active joints (p

Benign transient hyperphosphatasemia of infancy and early childhood is a self-limiting condition characterized by transiently increased serum alkaline phosphatase in the absence of liver, kidney or metabolic bone diseases. It is often accidentally found in children under five years old and it might be associated with a variety of underlying clinical disorders. Its pathophysiology remains unclear. Herein, we report a case of a 4-year-old girl with a 1-year history of persistent oligoarticular Juvenile Idiopathic Arthritis, who was found to have transient hyperphosphatasemia during a periodic check-up. This clinical case underlines the importance of promptly recognizing this benign condition, which avoids unnecessary extensive investigations.

OBJECTIVE: To update the recommendations for the treatment of Rheumatoid Arthritis (RA) with biological therapies, endorsed by the Portuguese Society of Rheumatology (SPR). METHODS: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. At a national meeting the 10 recommendations were discussed and updated. The document resulting from this meeting circulated to all Portuguese rheumatologists, who anonymously voted online on the level of agreement with the recommendations. RESULTS: These recommendations cover general aspects as shared decision, prospective registry in Reuma.pt, assessment of activity and RA impact and treatment objective. Consensus was also achieved regarding specific aspects as initiation of biologic therapy, assessment of response, switching and definition of persistent remission. CONCLUSION: These recommendations may be used for guidance of treatment with biological therapies in patients with RA. As more evidence becomes available and more therapies are licensed, these recommendations will be updated. publishersversion published

Objectives. To assess the effectiveness of subcutaneous Golimumab 50 mg/monthly combined with methotrexate (SC GLM + MTX) over 52 weeks of treatment, in biologic-naïve RA patients, in a multicentre nationwide cohort from the Rheumatic Diseases Portuguese Register (Reuma.pt). Methods. Data for this observational study was collected from March 2011 to August 2015. Disease activity (DAS28), functional capacity (HAQ) and Patient Global Disease Assessment (PGDA) were measured at baseline and weeks 12, 24 and 52 of treatment. The primary objective was clinical remission over 52 weeks (1 year) and secondary objectives were: functional response and functional remission over 52 weeks, variation of individual components of DAS over time and treatment persistence at week 52. Comparison between baseline variables of subjects with and without clinical remission was performed. The SC GLM + MTX persistence rate was estimated by the Kaplan-Meier analysis. Cox proportional hazard model approach was used to evaluate predictive factors of persistence, response and remission. Results. A total of 109 patients were enrolled in the study: 94 (86.2%) female, mean age 55.5±13.2 years, mean age at diagnosis 45.5±13.5 years, mean age at beginning of treatment with biologic agents 53.1±13.1 years; 78.1% positive for serum rheumatoid factor. All patients were biologic-naïve and had active disease, despite previous treatment with conventional DMARDs. At the time of this analysis, 93 patients had a follow-up time of at least 52 weeks (i.e. started treatment before August 2014). Of this group, 38.3% achieved clinical remission, 91.9% functional response and 35.2% functional remission, over 52 weeks. Treatment persistence was 75.3% at 1 year. Disease activity indices were all statistically significantly lower at 12, 24 and 52 weeks when compared to baseline. Older age at diagnosis was associated to a lower probability of clinical remission (HR= 0.96, p= 0.031) whereas higher C-reactive protein baseline levels were associated with a lower probability of functional response (HR= 0.54; p= 0.026). Conclusions. Golimumab 50 mg + MTX showed effectiveness in the treatment of patients with active RA, in accordance to what previously observed in clinical trials. A consistent and significant decrease in RA disease activity through 52 weeks of treatment and a significant functional improvement were observed, as well as a high persistence on treatment.

Background:Methotrexate (MTX) is the most widely used conventional synthetic disease-modifying antirheumatic drug (csDMARD) in the treatment of juvenile idiopathic arthritis (JIA).1,2When remission is achieved, questions remain about discontinuing MTX. There is some evidence that a longer period of inactive disease before MTX withdrawal is associated with lower likelihood of relapse, while both rheumatoid factor (RF) positive polyarthritis and extended oligoarthritis categories are associated with higher probability of disease relapse.2,3Objectives:To identify predictive factors of relapse after discontinuation of MTX in JIA patients with inactive disease.Methods:Prospective multicentre cohort study in patients diagnosed with JIA, according to the ILAR classification, using real world data from the Portuguese national register database, Reuma.pt (Fig 1).4We evaluated patients who have reached JADAS27 inactive disease (≤1 and no active extra-articular manifestations) and discontinued MTX before the age of 18 years-old.5Relapse was defined as recurrence (>1 or extra-articular manifestations) or restarting a DMARD.5To identify differences of relapse risk, univariate analyses were performed. Persistence in remission was estimated using the Kaplan-Meier method. Subsequently, Cox regression analyses were performed to identify predictors of relapse.Results:119 JIA patients discontinued MTX due to inactive disease (Fig 1). 69.7% were females and 60.6% had oligoarticular JIA. Sociodemographic and clinical characteristics are shown in Table 1. Relapse has occurred in 32.8%. Table 2 shows the disease characteristics at MTX initiation and discontinuation and at relapse or last visit.In univariate analysis, relapse was associated with the use of NSAIDs at the time of MTX discontinuation (p=.027) and with a period of less than two years in inactive disease before MTX suspension (p=.040). We found no association with gender, race, immunology (RF, antinuclear and cyclic citrullinated peptide antibodies), MTX dose, discontinuation modality (tapering and spacing the doses or just tapering the dose), extra-articular manifestations, previous corticotherapy, family history, body mass index, JADAS, CHAQ index, inflammatory parameters, tender and swollen joint counts at MTX initiation or discontinuation nor with age at remission or at MTX suspension. Median persistence in inactive disease was significantly higher in patients with more than two years in remission before MTX discontinuation (p=.034) and in those who did not use NSAIDs at time of MTX discontinuation (p=.026) (Fig 2).After adjustment for age at diagnosis, MTX tapering and JIA category, use of NSAIDs at the time of discontinuation (HR, 1.98 95%CI 1.03-3.82) and less than two years in remission (HR, 3.12 95%CI 1.35-7.13) remained associated with relapse.Conclusion:In this large cohort we found that the use of NSAIDs at the time of MTX discontinuation was associated with two times the likelihood of relapse. Like in other studies we also showed that the time in remission before MTX discontinuation is the main predictor of relapse. We found no association between the JIA category and the risk of relapse.References:[1]Hügle B 2016[2]Klotsche J 2018[3]Guzman J 2014[4]Canhão H 2011[6]Consolaro A 2014Disclosure of Interests:Soraia Azevedo: None declared, José Tavares-Costa: None declared, Ana Teresa Melo: None declared, Raquel Freitas: None declared, Marta Cabral: None declared, Marta Conde: None declared, Francisca Aguiar: None declared, Agna Neto: None declared, Ana Filipa Mourão: None declared, Filipa Oliveira-Ramos: None declared, Maria Jose Santos Speakers bureau: Novartis and Pfizer, Daniela Peixoto: None declared

Background Pain and stiffness are characteristic clinical features of axial Spondyloarthritis (axSpA), leading to functional impairment. Patients describe beneficial effects of physical activity, suggesting a possible involvement of muscle tissue. Body composition data in young axSpA patients with short disease duration are scarce and its implications in muscle strength are not yet clarified. Objectives The purpose of this study is to assess the muscle strength and body composition of different body segments (trunk, upper and lower limbs), in patients with axSpA and to compare them with healthy controls. Methods Patients with clinical diagnosis of axSpA meeting the ASAS classification criteria, aged 18 to 50 years, with symptoms duration ≤ 10 years, were included in this study. Healthy individuals matched by gender and age (1:1) were used as control group (HC). Muscle strength was measured by resisted hand-held dynamometer performed by a single reader, in three different body segments: trunk, upper and lower limbs (on both sides). The mean strength of right and left, upper and lower limbs, was calculated and used in the analysis. Strength of each body segment was also normalized to the total lean mass (LM) of the respective segment. Body composition was measured by octapolar multifrequency bioelectrical impedance analysis (InBody770). Physical activity was assessed by the International Physical Activity Questionnaire (IPAQ). Fisher’s exact test or chi-square test and Mann-Whitney U test were used to compare differences between groups. Results A total of 27 axSpA patients and 27 HC were included. Mean age was 36.5 ± 1.0 years, 67% were males. There was no significant difference between both groups in terms of age, gender, body mass index and physical activity. AxSpA patients had a mean symptoms duration of 7.0 ± 0.9 years. AxSpA patients had lower muscle strength in the upper limbs (50.55 ± 31.60 vs 71.70±31.41 p=0.023) and lower limbs (52.25±18.45 vs 59.83±9.75, p=0.001), compared to HC. Trunk muscle strength did not show any difference between groups (59.10±26.1 vs 56.45±11.2, p=0.856). There were no significant differences in LM and body water, between both groups, for each segment (upper limbs, lower limbs and trunk). Fat mass was significantly higher in the trunk (10.90±8.80 vs 8.10±5.83, p=0.035) and upper limbs (1.40±1.35 vs 0.88±1.0, p=0.05) of axSpA patients, but not in the lower limbs (3.10±1.90 vs 2.45±1.68, p=0.157). Normalized appendicular muscle strength was lower in axSpA patients (upper limbs: 18.63±8.25 vs 21.21±5.92, p=0.018) (Table). Conclusion Young patients with short duration have reduced appendicular muscle strength, compared to HC, with no differences in LM, suggesting a possible muscle dysfunction. Further studies are needed to confirm these findings and understand the underlying pathophysiological mechanisms. Disclosure of Interests Agna Neto: None declared, Rita Pinheiro Torres: None declared, Lucia Domingues: None declared, Diana Teixeira: None declared, Santiago Rodrigues-Manica Grant/research support from: Novartis, MSD, Speakers bureau: Novartis, Jose Marona: None declared, Carina Lopes: None declared, Joao Lagoas Gomes: None declared, Tiago Costa: None declared, Maria Joao Goncalves: None declared, Ines Silva: None declared, Paula Carreto: None declared, Walter Castelao: None declared, Margarida Mateus: None declared, Manuela Costa: None declared, Sandra Falcao: None declared, Ana Filipa Mourao: None declared, Atlas Sardoo: None declared, Sara Maia: None declared, Conceicao Calhau: None declared, Jaime Branco: None declared, Fernando Pimentel dos Santos Grant/research support from: From Abbvie and Novartis, Speakers bureau: Abbvie, Novartis, Pfizer, Biogen

Background:The outcomes of the infection by the SARS-CoV-2 in patients with immune-mediated inflammatory diseases were largely unknown during the early days of the COVID-19 pandemic. It was hypothesized that these patients were at higher risk of morbidity and mortality due to their inherent immune dysfunction and immunosuppressive therapy. Several rheumatology societies issued recommendations urging patients not to stop their anti-rheumatic treatments.Objectives:To assess treatment compliance of patients with rheumatoid arthritis (RA) during the first wave of the SARS-CoV-2/COVID-19 pandemic in Portugal.Methods:The web-based survey COVIDRA (COVID in RA) was developed to assess the impact of the first wave mandatory confinement in patients with RA focusing on 5 domains: RA symptoms, attitudes towards medication, employment status, physical exercise and mental health. The questionnaire was sent to RA patients through e-mail and social media of the Portuguese Society of Rheumatology and two patient associations; and it was filled locally at two rheumatology centers in Lisbon. Recruitment took place during June and July 2020. Descriptive statistics were generated by the survey software and were afterwards transported and evaluated using appropriate biostatistics software.Results:We obtained 441 valid questionnaires. Most respondents were female (88.4%), caucasian (93.6%), with a mean age of 58 (+/-13) years. The majority (57.6%) had longstanding disease (>10 years) and were treated with csDMARDs (63.2%) and/or bDMARDs/tsDMARDS (23,7%). Only 14% (N=61) discontinued or reduced the dosage or frequency of their RA treatment. Most of these changes were previously planned by the attending physician (27.9%). Only 11 patients (18%) discontinued their immunosuppressive medication out of fear of becoming infected with SARS-CoV-2 (corresponding to 2.5% of total responders). Another 11 patients did so because they had no prescription, couldn’t go to the community/hospital pharmacy or couldn’t afford the medication. Although these numbers preclude any statistical analysis, when compared to patients who persisted on their treatment, those discontinuing due to fear of contagion were younger (56.4 vs 58.5 years), all female (100 vs 86.8%), with long-lasting disease (≥ 11 years) (90.9% vs 57.5%), more frequently treated with bDMARDs (36.4 vs 23.1%) and presenting more symptoms of depression (54.5 vs 49.7%).Conclusion:Most RA patients complied with their treatment during the first wave of the SARS-CoV-2 pandemic in Portugal. Only a minority changed their immunosuppressive treatment due to fear of SARS-CoV-2 infection. Very similar rates of immunosuppressive discontinuation due to fear of contagion were reported by other authors (such as Schmeiser et al, Pineda-sic et al and Fragoulis et al).Disclosure of Interests:Filipe Araujo Speakers bureau: Pfizer, Biogen, Novartis, Menarini, Consultant of: MSD, Nuno Gonçalves: None declared, Ana Filipa Mourão: None declared.

Background:Juvenile idiopathic arthritis (JIA), one of the most common chronic diseases in children, can be classified in seven different categories according to its onset presentation. Concerns about pregnancy outcomes play a secondary role in disease approach. However, recent data showed an increased risk of pre-term birth in women with JIA instead the small patient samples analysed.Objectives:In this review, our aim is to describe the current available knowledge on JIA adverse, maternal and fetal, outcomes.Methods:A systematic literature review was conducted since January of 2000 until December 2020, by searching the PubMed and Embase bibliographic databases. The search was limited to articles in English language, presenting a comparator group (healthy individuals or patients without known auto-immune rheumatic diseases) and at least one clinical outcome of interest. Two independent reviewers screened the titles and abstracts followed by a full-text review to assess papers regarding their eligibility.Results:Ten observational studies out of 1560 references, fulfilled the inclusion criteria, of which, 9 were retrospective and 1 prospective. A total of 6.214 women with JIA (with 6.811 pregnancies) and 18.659.513 healthy controls (with 21.339.194 pregnancies) were included in this review.Concerning maternal outcomes, delivery by caesarian section (CS) was more frequent among JIA women (in 4 out of 6 studies). Pre-eclampsia was referred in 3 out of 6 studies and a higher risk of vaginal bleeding and placenta previa in one additional study. No study found an increased risk for gestational diabetes or hypertension in pregnant women with JIA.Regarding fetal outcomes, 8 studies revealed significantly increased of pre-term birth (only in first births in one study) but one study didn’t show any increased risk. Two studies showed a higher risk of small gestational age (SGA) and in another 2, increased risk for low birth weight (LBW). No evidence of increased risk of major congenital malformations.Conclusion:This systematic review suggests an increased risk for pre-eclampsia, preterm birth, delivery by CS, SGA and LBW, among pregnant women with JIA. Conclusions should be carefully interpreted, giving the heterogeneity of studied populations regarding demography, disease type, disease activity, and prescribed medication.Disclosure of Interests:None declared

Currently, there are no specific markers for juvenile idiopathic arthritis (JIA) diagnosis, which is based on clinical symptoms and some blood tests for diseases' exclusion. Aiming to select new epitope-based antigens (mimotopes) that could recognize circulating autoantibodies in most JIA forms, we screened a phage displayed random peptide library against IgG antibodies purified from serum of JIA patients. ELISA assay was carried out to confirm immunoreactivity of selected peptides against sera IgG antibodies from JIA patients, healthy children and patients with other autoimmune diseases. The mimotope PRF+1 fused to phage particles was able to efficiently discriminate JIA patients from controls, and for this reason was chosen to be chemically synthesized for validation in a larger sample size. The synthetic peptide was immobilized onto bioelectrodes' surface for antibody detection by electrochemical analyses through differential pulse voltammetry. The PRF+1 synthetic peptide has efficiently discriminated JIA patients from control groups (p0.0001) with a very good accuracy (AUC0.84; sensitivity=61%; specificity=91%). The electrochemical platform proved to be fast, low cost and effective in detecting anti-PRF+1 antibodies from JIA patients compared to healthy controls (p=0.0049). Our study describes a novel and promising epitope-based biomarker for JIA diagnosis that can become a useful tool for screening tests, which was successfully incorporated onto an electrochemical biosensor and could be promptly used in field diagnostics.

Background A BASDAI ≥4 has been often required to start TNFi therapy in patients with axSpA. However, this cut-off of high disease activity (HDA) is largely arbitrary. Unlike BASDAI, ASDAS incorporates objective measures (e.g. CRP) and has a validated definition of HDA (≥2.1). It has thus been suggested that ASDAS could also be used to guide treatment decisions, but evidence to support this is still scarce. Objectives To compare the impact of applying the ASDAS and BASDAI definitions of HDA in selecting patients for TNFi-treatment in daily clinical practice Methods Patients from Reuma.pt (Rheumatic Diseases Portuguese Register), with diagnosis of axSpA according to their rheumatologists (both treated and not treated with their first TNFi), with complete baseline BASDAI and ASDAS data, and complete 6 month of follow-up (i.e. baseline, 3 and 6 months visits available) were included. Four subgroups [cross-tabulation between ASDAS (≥2.1) and BASDAI (≥4) definitions of HDA], were compared according to baseline demographic and clinical characteristics in the ‘eligible population’ (i.e. irrespective of TNFi-treatment). In addition, for patients starting TNFi and with complete follow-up BASDAI/ASDAS data (‘efficacy population’), the subgroups were also compared according to different response criteria (see table 1), at 3 and 6 months. Results In total, 466 patients were included (59% males and 66% HLA-B27 positive). The large majority (n=382; 82%) fulfilled the definition of HDA according to both BASDAI and ASDAS at baseline (i.e. BASDAI≥4 and ASDAS≥2.1). The frequency of ASDAS≥2.1, if BASDAI Conclusions Our results show that the ASDAS-HDA definition (ASDAS≥2.1) is more inclusive than the BASDAI-HDA definition (≥4) in selecting axSpA patients for TNFi treatment. Importantly, the additionally ‘captured’ patients respond better and have higher likelihood of predictors thereof. These results support the use of ASDAS≥2.1 as a selection criterion for treatment decisions. Acknowledgements Supported in part by a research Grant from Investigator-Initiated Studies program of MSD Disclosure of Interest J. Marona Grant/research support from: MSD, A. Sepriano Grant/research support from: MSD, S. Rodrigues-Manica Grant/research support from: MSD, F. Pimentel-Santos Grant/research support from: MSD, A. Mourao Grant/research support from: MSD, N. Gouveia Grant/research support from: MSD, J. Branco Grant/research support from: MSD, F. Vinagre Grant/research support from: MSD, R. Roque Grant/research support from: MSD, J. Rovisco Grant/research support from: MSD, M. Marques Grant/research support from: MSD, J. Tavares-Costa Grant/research support from: MSD, J. Silva Grant/research support from: MSD, H. Santos Grant/research support from: MSD, N. Madeira Grant/research support from: MSD, E. Vieira-Sousa Grant/research support from: MSD, R. Machado Grant/research support from: MSD, M. Bernardes Grant/research support from: MSD, R. Ferreira Grant/research support from: MSD, S. Ramiro Grant/research support from: MSD

Background: Advances in osteoporosis (OP)case definition, treatment options, optimal therapy duration and pharmacoeconomic evidence in the national context motivated the Portuguese Society of Rheumatology (SPR) to update the Portuguese recommendations for the diagnosis and management of osteoporosis published in 2007. Methods: SPR bone diseases’ working group organized meetings involving 55 participants (rheumatologists, rheumatology fellows and one OP specialist nurse) to debate and develop the document. First, the working group selected 11 pertinent clinical questions for the diagnosis and management of osteoporosis in standard clinical practice. Then, each question was investigated through literature review and draft recommendations were built through consensus. When insufficient evidence was available, recommendations were based on experts’ opinion and on good clinical practice. At two national meetings, the recommendations were discussed and updated. A draft of the recommendations full text was submitted to critical review among the working group and suggestions were incorporated. A final version was circulated among all Portuguese rheumatologists before publication and the level of agreement was anonymously assessed using an online survey. Results: The 2018 SPR recommendations provide comprehensive guidance on osteoporosis prevention, diagnosis, fracture risk assessment, pharmacological treatment initiation, therapy options and duration of treatment, based on the best available evidence. They attained desirable agreement among Portuguese rheumatologists. As more evidence becomes available, periodic revisions will be performed. Target audience and patient population: The target audience for these guidelines includes all clinicians. The target patient population includes adult Portuguese people. Intended use: These recommendations provide general guidance for typical cases. They may not be appropriate in all situations - clinicians are encouraged to consider this information together with updated evidence and their best clinical judgment in individual cases.

Objective: To update the recommendations for the treatment of rheumatoid arthritis (RA) with biological therapies, endorsed by the Portuguese Society of Rheu -matology (SPR). Methods: These treatment recommendations were formulated by Portuguese rheumatologists based on litera -ture evidence and consensus opinion. At a national meeting the 11 recommendations were discussed and updated. The document resulting from this meeting circulated to all Portuguese rheumatologists, who anonymously voted online on the level of agreement with the recommendations. Results: These recommendations cover general aspects as shared decision, prospective registry in Reuma.pt, asses sment of activity and RA impact and treatment objec tive. Consensus was also achieved regarding specific aspects as initiation of biologic therapy, assessment of res pon se, switching and definition of persistent remission. Conclusion: These recommendations may be used for guidance of treatment with biological therapies in patients with RA. As more evidence becomes available and more therapies are licensed, these recommendations will be updated. publishersversion published

Background Persistence on medication mainly reflects both effectiveness and safety of a drug. Understanding the reasons to stop bDMARD in routine clinical practice can help to better define the efficacy and safety of biologic medications in children with juvenile idiopathic arthritis (JIA). Objectives To investigate persistence on treatment and the reasons for discontinuation of the first biological in patients with JIA. Methods Portuguese patients with JIA registered in Reuma.pt who started a bDMARD were analyzed. Persistence was defined as the time between treatment initiation and discontinuation of the first bDMARD. The mean time until discontinuation was calculated using Cox regression survival estimates and the reasons for discontinuation of the first bDMARD were registered. Results Of the 1724 JIA patients registered in Reuma.pt, 319 received biological therapy, 62% (198) female. The mean age at disease onset was 7.7±4.8 years and the mean time between the beginning of JIA and the first bDMARD was 8.2±9.4 years. The mean disease duration was 13.7±10.7 years and the mean age at the beginning of biological therapy was 15.8±9.4 years. The distribution of JIA subtypes was: 19.1% polyarticular RF-negative, 17.2% enthesitis-related arthritis, 16.6% polyarticular RF-positive, 16% extended oligoarticular, 13.5% persistent oligoarticular, 12% systemic JIA and 0.9% had undifferentiated arthritis. Considering the whole group, 53.2% have had extra-articular manifestations and 18.4% have or had had uveitis since the beginning of the disease. Persistence on treatment, before discontinuation (due to any cause) was 34.7 months (range: 0.03–182 months) adjusted for gender, biological therapy, JIA subtype, age at the beginning of biological therapy, and disease duration until initiating first bDMARD. The major reasons for drug discontinuation was inefficacy (49.6%), remission (14.2%), adverse events (10.6%), patient decision (1.6%) and pregnancy planning (1.4%). In 22.7% the reason was not specified. Conclusions Almost half of the JIA patients stop the first biological agent, due to lack of response, reinforcing the need for the existence of several treatment options fully studied in JIA. Disclosure of Interest None declared

BACKGROUND: Methotrexate (MTX) is the first-line drug in the treatment of rheumatoid arthritis (RA) and the most commonly prescribed disease modifying anti-rheumatic drug. Moreover, it is also used as an adjuvant drug in patients under biologic therapies, enhancing the efficacy of biologic agents. OBJECTIVES: To review the literature and update the Portuguese recommendations for the use of MTX in rheumatic diseases first published in 2009. METHODS: The first Portuguese guidelines for the use of MTX in rheumatic diseases were published in 2009 and were integrated in the multinational 3E Initiative (Evidence Expertise Exchange) project. The Portuguese rheumatologists based on literature evidence and consensus opinion formulated 13 recommendations. At a national meeting, the recommendations included in this document were further discussed and updated. The document resulting from this meeting circulated to all Portuguese rheumatologists, who anonymously voted online on the level of agreement with the updated recommendations. RESULTS: Results presented in this article are mainly in accordance with previous guidelines, with some new information regarding hepatitis B infection during MTX treatment, pulmonary toxicity monitoring, hepatotoxicity management, association with hematologic neoplasms, combination therapy and tuberculosis screening during treatment. CONCLUSION: The present recommendations combine scientific evidence with expert opinion and attained desirable agreement among Portuguese rheumatologists. The regular update of these recommendations is essential in order to keep them a valid and useful tool in daily practice. publishersversion published

Fabry's disease (FD) is a lysosomal storage disorder associated with an alpha-galactosidase A deficiency. The prevalence of FD among juvenile idiopathic arthritis (JIA) patients with established diagnosis is unknown, but as musculoskeletal pain may be an important complaint at presentation, misdiagnosed cases are anticipated. With this study, we aim to calculate the frequency of FD-associated mutations in a cohort of JIA patients. Children with JIA from a national cohort were selected. Clinical and laboratorial information was recorded in the Portuguese rheumatic diseases register (http://Reuma.pt). Molecular genetic testing to detectGLAgene mutations was performed. After the multiplex polymerase chain reactions technique for DNA amplification, direct sequencing of the complete sequence ofGLAgene was completed. From a cohort of 292 patients with JIA (188 females, 104 males), mutations were identified in 5 patients (all female). Four patients had the mutation D313Y, a rareGLAvariant, which is associated with low enzymatic levels in plasma, but normal lysosomal levels. One patient presented the missense mutation R118C, which was previously described in Mediterranean patients with FD. This is the first screening of FD mutations in a cohort of JIA patients. No "classic" pathogenic FD mutations were reported. The late-onset FD-associated mutation, R118C, was found in a frequency of 0.34% (1/292). publishersversion published

Objective Our aims were to evaluate the correlation between Juvenile Arthritis Disease Activity Score 27-joint reduced count (JADAS27) with erythrocyte sedimentation rate (ESR) and JADAS27 with C-reactive protein (CRP) scores and to test the agreement of both scores on classifying each disease activity state. We also aimed at verifying the correlation of the 2 scores across juvenile idiopathic arthritis (JIA) categories and to check the correlation between JADAS27-ESR and clinical JADAS27 (JADAS27 without ESR). Methods A nationwide cohort of patients with JIA registered in the Portuguese Register, Reuma.pt, was studied. JADAS27-CRP was adapted by replacing ESR with CRP level as the inflammatory marker. JADAS27-CRP was calculated similarly to JADAS27-ESR as the simple linear sum of its 4 components. Pearson's correlations and K statistics were used in the analyses. Results A total of 358 children had full data to calculate JADAS27; 65.4% were female and the mean ± SD disease duration was 11.8 ± 9.1 years. The correlation coefficient between JADAS27-ESR and JADAS27-CRP was 0.967 (P < 0.0001), although the correlation coefficient between ESR and CRP level was 0.335 (P < 0.0001). The strong correlation between JADAS27-ESR and JADAS27-CRP was maintained when compared within each JIA category. The agreement between JADAS27-ESR and JADAS27-CRP across the 4 activity states was very good, showing 91.1% of the observations in agreement; K = 0.867 (95% confidence interval 0.824–0.91). The correlation between JADAS27 with ESR and JADAS27 without ESR was high (r = 0.97, P < 0.0001). Conclusion JADAS27 based on CRP level correlated closely with JADAS27-ESR across all disease activity states and JIA categories, indicating that both measures can be used in clinical practice. Moreover, the correlation of JADAS27 with and without ESR was also high, suggesting that this tool might be useful even in the absence of laboratorial measures.

Human leukocyte antigen (HLA)-B27 is the mostly known major histocompatibility complex (MHC) gene associated with ankylosing spondylitis (AS). Nonetheless, there is substantial evidence that other MHC genes appear to be associated with the disease, although it has not yet been established whether these associations are driven by direct associations or by linkage disequilibrium (LD) mechanisms. We aimed to investigate the contributions of HLA class I and II alleles and B27-haplotypes for AS in a case-control study. A total of 188 HLA-B27 AS cases and 189 HLA-B27 healthy controls were selected and typed for HLA class I and II by the Luminex polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. Allelic and haplotypic distributions were estimated by maximum likelihood method using Arlequin v3.11 and statistical analysis were performed by Stata10.1. No associations were found between non-HLA-B27 loci and AS susceptibility, but several associations were observed for phenotypic features of the disease. DRB1*08 was identified as a risk factor for uveitis and DQB1*04 seems to provide protection for AS severity (functional, metrological and radiological indexes). A*02/B27/C*02/DRB1*01/DQB1*05 [P

The Journal of Rheumatology Copyright © 2013. All rights reserved., Objective: B cells play important roles in rheumatoid arthritis (RA). Given the beneficial effect of B cell depletion therapy in RA as well as the observed alterations in B cell subpopulations in this disease, we evaluated whether changes in the expression of genes related to B cell survival and activation were already present in patients with untreated very early RA (VERA; < 6 weeks of disease duration). Methods: The expression of a group of B cell-related activation and survival genes was quantified in peripheral blood mononuclear cells from patients with VERA by real-time PCR and compared with untreated early RA (< 1 year), established treated RA, and other untreated early arthritis conditions. Serum B cell-activating factor belonging to the tumor necrosis factor family (BAFF) was quantified by ELISA. Results: BAFF gene expression and serum levels were highest in patients with VERA. The expression of BAFF receptor (BAFF-R) increased with disease progression, while transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) was elevated since the first weeks of RA onset. Paired box 5 gene expression was also increased at all RA stages. Chemokine (C-X-C motif) receptor 5 was elevated only in established RA. No differences were observed in B cell maturation antigen, activation-induced cytidine deaminase, B lymphocyte-induced maturation protein, and B cell lymphoma 2 expression. Conclusion: Disturbances in the expression of B cell-related activation and survival genes, particularly BAFF and TACI, occur from the onset of RA and precede changes in BAFF-R. These alterations can lead to the development of autoreactive B cells from the first weeks of RA onset., Supported by a grant from Sociedade Portuguesa de Reumatologia/Schering-Plough 2005. RAM was funded by a fellowship from Fundação para a Ciência e a Tecnologia (SFRH/BD/30247/2006).

Introduction: To provide evidence-based guidance for the rati onal and safe prescripti on of biological therapies in children and adolescents with juvenile idiopathic arthriti s (JIAs), considering the latest available evidence and the new licensed biologics. Methods: Rheumatologists and Pediatricians with experti se in Pediatric Rheumatology updated the recommendati ons endorsed by the Portuguese Society of Rheumatology and the Portuguese Society of Pediatrics based on published evidence and expert opinion. The level of agreement with fi nal propositi ons was voted using an online survey. Results: In total, 20 recommendati ons to guide the use of biological therapy in children and adolescents with JIAs are issued, comprising 4 general principles and 16 specifi c recommendati ons. A consensus was achieved regarding the eligibility and response criteria, maintenance of biological therapy, and procedures in case of non-response, for each JIA category. Specifi crecommendati ons concerning safety procedures were also updated. Discussion: These recommendati ons take into account the specifi citi es of each JIA category and are intended to conti nuously improve the management of JIA pati ents., Portuguese Journal of Pediatrics, Vol. 47 No. 4 (2016)

Objectives To determine how adult juvenile idiopathic arthritis (JIA) patients fulfil classification criteria for adult rheumatic diseases, evaluate their outcomes and determine clinical predictors of inactive disease, functional status and damage. Methods Patients with JIA registered on the Rheumatic Diseases Portuguese Register (Reuma.pt) older than 18 years and with more than 5 years of disease duration were included. Data regarding sociodemographic features, fulfilment of adult classification criteria, Health Assessment Questionnaire, Juvenile Arthritis Damage Index—articular (JADI-A) and Juvenile Arthritis Damage Index—extra-articular (JADI-E) damage index and disease activity were analysed. Results 426 patients were included. Most of patients with systemic JIA fulfilled criteria for Adult Still9s disease. 95.6% of the patients with rheumatoid factor (RF)-positive polyarthritis and 57.1% of the patients with RF-negative polyarthritis matched criteria for rheumatoid arthritis (RA). 38.9% of the patients with extended oligoarthritis were classified as RA while 34.8% of the patients with persistent oligoarthritis were classified as spondyloarthritis. Patients with enthesitis-related arthritis fulfilled criteria for spondyloarthritis in 94.7%. Patients with psoriatic arthritis maintained this classification. Patients with inactive disease had lower disease duration, lower diagnosis delay and corticosteroids exposure. Longer disease duration was associated with higher HAQ, JADI-A and JADI-E. Higher JADI-A was also associated with biological treatment and retirement due to JIA disability and higher JADI-E with corticosteroids exposure. Younger age at disease onset was predictive of higher HAQ, JADI-A and JADI-E and decreased the chance of inactive disease. Conclusions Most of the included patients fulfilled classification criteria for adult rheumatic diseases, maintain active disease and have functional impairment. Younger age at disease onset was predictive of higher disability and decreased the chance of inactive disease.

Funding Information: positions on two Pfizer sponsored trials and has directed an educational course supported by Bristol Myers Squibb. He serves as an epidemiology consultant to CORRONA. J.A.P.S. has received honoraria as a speaker or consultant and benefited from research support from several pharmaceutical companies involved in the production of biologic agents (Abbott, Amgen, MSD, Pfizer and Roche), always at sums less than E10 000. All other authors have declared no conflicts of interest. Funding Information: Funding: This work was supported by a grant from Harvard-Portugal Program HMSP-ICS/SAU-ICT/0002/ 2010. Objectives: Adalimumab, etanercept and infliximab are effective TNF inhibitors (TNFis) in the treatment of RA, but no randomized clinical trials have compared the three agents. Prior observational data are not consistent. We compared their effectiveness over 1 year in a prospective cohort.Methods: Analyses were performed on subjects' first episode of TNFi use in the Rheumatic Diseases Portuguese Register, Reuma.pt. The primary outcome was the proportion of patients with European League Against Rheumatism good response sustained at two consecutive observations separated by 3 months during the first year of TNFi use. Comparisons were performed using conventional adjusted logistic regression, as well as matching subjects across the three agents using a propensity score. In addition, baseline predictors of treatment response to TNFi were identified.Results: The study cohort included 617 RA patients, 250 starting etanercept, 206 infliximab and 161 adalimumab. Good response was achieved by 59.6% for adalimumab, 59.2% for etanercept and 51.9% for infliximab (P = 0.21). The modelled probability of good response did not significantly differ across agents (etanercept vs adalimumab OR = 0.97, 95% CI 0.55, 1.71; etanercept vs infliximab OR = 1.25, 95% CI 0.74, 2.12; infliximab vs adalimumab OR = 0.80, 95% CI 0.47, 1.36). Matched propensity score analyses also showed no significant treatment response differences. Greater educational attainment was a predictor of better response, while smoking, presence of ACPA, glucocorticoid use and worse physician assessment of disease activity at baseline each predicted a reduced likelihood of treatment response.Conclusion: Over 1 year, we found no difference in effectiveness between adalimumab, etanercept and infliximab. publishersversion published

Objective.Unconfirmed reports describe association of ankylosing spondylitis (AS) with several candidate genes includingANKH. Cellular export of inorganic pyrophosphate is regulated by the ANK protein, and mutant mice (ank/ank), which have a premature stop codon in the 3’ end of theankgene, develop severe ankylosis. We tested the association between single-nucleotide polymorphisms (SNP) in these genes and susceptibility to AS in a population of patients with AS. We investigated the role of these genes in terms of functional (BASFI) and metrological (BASMI) measures, and the association with radiological severity (mSASSS).Methods.Our study was conducted on 355 patients with AS and 95 ethnically matched healthy controls. AS was defined according to the modified New York criteria. Four SNP inANKH(rs27356, rs26307, rs25957, and rs28006) were genotyped. Association analysis was performed using Cochrane-Armitage and linear regression tests for dichotomous and quantitative variables. Analyses of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASFI, and mSASSS were controlled for sex and disease duration.Results.None of the 4 markers showed significant single-locus disease associations (p > 0.05), suggesting thatANKHwas not a major determinant of AS susceptibility in our population. No association was observed between these SNP and age at symptom onset, BASDAI, BASFI, BASMI, or mSASSS.Conclusion.These results confirm data in white Europeans thatANKHis probably not a major determinant of susceptibility to AS.ANKHpolymorphisms do not markedly influence AS disease severity, as measured by BASMI and mSASSS.

Ankylosing spondylitis (AS) is a chronic inflammatory disease in which genetic factors play a central role. The efficacy of TNF blockers has reoriented research in this field in order to explain the influence of TNF in AS pathogenesis. The objective of this study was to access the influence of single nucleotide polymorphisms (SNPs) at positions -308 and -238 of the promoter region of TNF gene on AS susceptibility and prognosis. SNPs were determined by restriction fragment length polymorphisms in patients and controls. AS patients exhibited a decreased frequency of the A allele at position -238 (10%) when compared with controls (18%), suggesting that this could be a protective factor for disease susceptibility. In addition, the -308 GA/AA genotypes were associated with later disease onset in AS patients. These results suggest that TNF gene promoter polymorphisms at positions -238 and -308 could have a small influence on AS susceptibility and prognosis.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/, Objectives To estimate the national prevalence of rheumatic and musculoskeletal diseases (RMDs) in the adult Portuguese population and to determine their impact on health-related quality of life (HRQoL), physical function, anxiety and depression. Methods EpiReumaPt is a national health survey with a three-stage approach. First, 10 661 adult participants were randomly selected. Trained interviewers undertook structured face-to-face questionnaires that included screening for RMDs and assessments of health-related quality of life, physical function, anxiety and depression. Second, positive screenings for ≥1 RMD plus 20% negative screenings were invited to be evaluated by a rheumatologist. Finally, three rheumatologists revised all the information and confirmed the diagnoses according to validated criteria. Estimates were computed as weighted proportions, taking the sampling design into account. Results The disease-specific prevalence rates (and 95% CIs) of RMDs in the adult Portuguese population were: low back pain, 26.4% (23.3% to 29.5%); periarticular disease, 15.8% (13.5% to 18.0%); knee osteoarthritis (OA), 12.4% (11.0% to 13.8%); osteoporosis, 10.2% (9.0% to 11.3%); hand OA, 8.7% (7.5% to 9.9%); hip OA, 2.9% (2.3% to 3.6%); fibromyalgia, 1.7% (1.1% to 2.1%); spondyloarthritis, 1.6% (1.2% to 2.1%); gout, 1.3% (1.0% to 1.6%); rheumatoid arthritis, 0.7% (0.5% to 0.9%); systemic lupus erythaematosus, 0.1% (0.1% to 0.2%) and polymyalgia rheumatica, 0.1% (0.0% to 0.2%). After multivariable adjustment, participants with RMDs had significantly lower EQ5D scores (β=−0.09; p, EpiReumaPt was supported by a grant from Direcção-Geral da Saúde and was sponsored by: Fundação Calouste Gulbenkian, Fundação Champalimaud, Fundação AstraZeneca, Abbott, Merck Sharp & Dohme, Pfizer, Roche, Servier, Bial, D3A Medical Systems, Happybrands, Centro de Medicina Laboratorial Germano de Sousa, CAL-Clínica, Galp Energia, Açoreana Seguros and individual Rheumatologists.

OBJECTIVES Assess the effectiveness and safety of biologic therapy as well as predictors of response at 1 year of therapy, retention rate in biologic treatment and predictors of drug discontinuation in JIA patients in the Portuguese register of rheumatic diseases. METHODS We prospectively collected patient and disease characteristics from patients with JIA who started biological therapy. Adverse events were collected during the follow-up period. Predictors of response at 1 year and drug retention rates were assessed at 4 years of treatment for the first biologic agent. RESULTS A total of 812 JIA patients [65% females, mean age at JIA onset 6.9 years (s.d. 4.7)], 227 received biologic therapy; 205 patients (90.3%) were treated with an anti-TNF as the first biologic. All the parameters used to evaluate disease activity, namely number of active joints, ESR and Childhood HAQ/HAQ, decreased significantly at 6 months and 1 year of treatment. The mean reduction in Juvenile Disease Activity Score 10 (JADAS10) after 1 year of treatment was 10.4 (s.d. 7.4). According to the definition of improvement using the JADAS10 score, 83.3% respond to biologic therapy after 1 year. Fourteen patients discontinued biologic therapies due to adverse events. Retention rates were 92.9% at 1 year, 85.5% at 2 years, 78.4% at 3 years and 68.1% at 4 years of treatment. Among all JIA subtypes, only concomitant therapy with corticosteroids was found to be univariately associated with withdrawal of biologic treatment (P = 0.016). CONCLUSION Biologic therapies seem effective and safe in patients with JIA. In addition, the retention rates for the first biologic agent are high throughout 4 years.

Juvenile idiopathic arthritis (JIA) refers to a heterogeneous group of illnesses that have in common the occurrence of chronic joint inflammation in children younger than 16 years of age. The diagnosis is made only on clinical assessment. The identification of antibody markers could improve the early diagnosis, optimizing the clinical management of patients. Type II collagen is one potential autoantigen that has been implicated in the process of arthritis development. The aims of our study were to investigate the occurrence of anti-type II collagen antibodies and also to determine the avidity of the antibody–antigen binding. Ninety-six patients with oligoarticular or polyarticular JIA, 13 patients with ankylosing spondylitis (AS) and 61 healthy controls (HC) were tested for anti-type II collagen antibodies by ELISA and avidity ELISA. Sensitivity and specificity were determined by the receiver operating characteristic (ROC) curve analysis. Forty-two JIA patients (44%) were positive for antibodies against type II collagen. Its detection was significantly higher in JIA patients than in AS patients (p=0.006) and HCs (p

Copyright © 2015 Ana Filipa Mourão et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited., Introduction: This study aimed to assess the genetic determinants of poor outcome in Portuguese patients with juvenile idiopathic arthritis (JIA). Methods: Our study was conducted in Reuma.pt, the Rheumatic Diseases Portuguese Register, which includes patients with JIA. We collected prospectively patient and disease characteristics and a blood sample for DNA analysis. Poor prognosis was defined as CHAQ/HAQ >0.75 at the last visit and/or the treatment with biological therapy. A selected panel of single nucleotide polymorphisms (SNPs) associated with susceptibility was studied to verify if there was association with poor prognosis. Results: Of the 812 patients with JIA registered in Reuma.pt, 267 had a blood sample and registered information used to define "poor prognosis." In univariate analysis, we found significant associations with poor prognosis for allele A of TNFA1P3/20 rs6920220, allele G of TRAF1/C5 rs3761847, and allele G of PTPN2 rs7234029. In multivariate models, the associations with TRAF1/C5 (1.96 [1.17-3.3]) remained significant at the 5% level, while TNFA1P3/20 and PTPN2 were no longer significant. Nevertheless, none of associations found was significant after the Bonferroni correction was applied. Conclusion: Our study does not confirm the association between a panel of selected SNP and poor prognosis in Portuguese patients with JIA.

Objective. To compare the clinical results after treatment with B-cell depleting therapy in patients with membranous (WHO Class V) vs proliferative (WHO Class III or IV) lupus nephritis (LN). Methods. Data were compiled from two European centres on all patients with LN who were treated with i.v. rituximab (RTX) in a combination protocol with i.v. cyclophosphamide and steroids. Laboratory and serological evaluations were performed at 3, 6 and 12 months of follow-up. No immunosuppressive drugs were given before B-cell repopulation. Results. Forty-three patients, 28 with proliferate and 15 with membranous LN by renal biopsy, were evaluated. Six months after treatment with RTX, both the membranous and the proliferative LN patients had a significant reduction in proteinuria and an increase in serum albumin. The main improvements were observed during the first 6 months and only minor non-significant changes in albumin and proteinuria were observed thereafter. As expected, the patients with membranous nephritis had lower anti-dsDNA titres and higher complement C3 levels at baseline, but in both groups a significant reduction in anti-dsDNA titre and improvements in complement C3 levels were seen during the first 6 months after treatment; the kinetics of improvement were similar in both groups. Conclusion. The clinical course following B-cell depleting therapy is strikingly similar between patients with membranous and those with proliferative LN. These observational data suggest that, if controlled studies confirm the efficacy of B-cell depleting therapy in proliferative nephritis, clinicians may reasonably consider such therapy in membranous LN.

The identification of predictive factors of poor response to methotrexate (MTX) in juvenile idiopathic arthritis (JIA) patients could contribute to optimize the treatment strategy, namely by the earlier introduction of biological treatments.