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Paulo César Martins Urbano,1 Vanete Thomaz Soccol,1 Valderilio Feijó Azevedo2 1Biotechnology and Bioprocess Engineering Program, Federal University of Parana, Curitiba, Parana, Brazil; 2Hospital de Clínicas, Federal University of Parana, Curitiba, Parana, Brazil Abstract: Various criteria are necessary to assess the efficacy and safety of biological medications in order to grant companies the right to register these medications with the appropriate bodies that regulate their sale. The imminent expiration of the patents on reference biological products which block the cytokine TNF-α (tumor necrosis factor-α) raises the possibility of bringing so-called biosimilars to the market (similar to the biologicals of reference products). This occurrence is inevitable, but criteria to adequately evaluate these medications are now needed. Even among controversy, there is a demand from publications correlating the pro-apoptotic mechanism of the original TNF-α antagonists (etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol) in the treatment of rheumatoid arthritis and other diseases. In this article, the authors discuss the possibility of utilizing the pro-apoptotic effect correlated with the regulation of the anti-apoptotic proteins FLIP and NF-κB as new criteria for analyzing the pharmacodynamics of possible biosimilar TNF-α antagonists which should be submitted to regulatory agencies for evaluation. Keywords: anti-TNF drugs, rheumatoid arthritis, apoptosis, NF-κB, FLIP

Introduction: We evaluated the impact of gender on disease severity, health-related quality of life (HRQoL), treatment management, and patient-healthcare professional (HCP) interactions from the perspectives of patients with psoriatic arthritis (PsA)., Methods: Data were collected from a global online patient survey conducted by The Harris Poll (November 2, 2017 to March 12, 2018). Eligible patients were aged ≥ 18 years, with a self-reported diagnosis of PsA for > 1 year, had visited a rheumatologist/dermatologist in the past 12 months, and had reported previously using ≥ 1 conventional synthetic or biologic disease-modifying antirheumatic drug. Data were stratified by gender and analyzed descriptively, inferentially by binomial (chi-square) tests, and by multivariate logistic regression models., Results: Data from 1286 patients who participated were included: 52% were female, 48% were male. Varying perceptions of disease severity between males and females were indicated by differences in symptoms leading to a diagnosis of PsA, and in symptoms reported despite treatment; more females than males reported joint tenderness, skin patches/plaques, and enthesitis. More females than males reported a major/moderate impact of PsA on their physical activity and emotional/mental well-being. Reasons for switching medication differed between genders, with more females switching because they perceived their medication to not be effective enough related to their joint symptoms. More females than males were very satisfied with their communication with their rheumatologist and were more likely to discuss the impact of PsA on their daily lives, their treatment satisfaction, and treatment goals with their rheumatologist., Conclusions: Patients' perceptions of the impact of PsA on HRQoL, treatment management, and interactions with HCPs varied between males and females. More females than males reported major/moderate physical and emotional impacts of PsA. When treating patients, it is important for HCPs to consider the potential impact of gender on patients' experience of PsA and its symptoms. Graphical plain language summary available for this article., (© 2024. The Author(s).)

Background: Psoriatic arthritis can involve several domains. Due to its multifaceted nature and its frequent comorbidities such as depression, obesity, osteoarthritis and fibromyalgia, it is difficult to monitor these patients because the clinical scores involve subjective data. High-resolution ultrasound probes allowed the evaluation of more superficial structures, such as the nails and their synovio-entheseal framework, in close relationship with the enthesis of the distal extensor digitorum tendon. Nail ultrasound studies vary in terms of the parameters and fingers studied and in their findings., Objectives: To describe the most significant sonographic nail changes and the most affected fingers in psoriatic arthritis and to verify the association of nail ultrasound findings with clinical scores (nail psoriasis severity index (NAPSI), ankylosing spondylitis disease activity score with C-reactive protein (ASDAS-CRP), minimal disease activity (MDA), disease activity index for psoriatic arthritis (DAPSA))., Methods: This was a cross-sectional study with 52 patients with psoriatic arthritis at the Hospital de Clínicas do Paraná and 50 controls. A total of 1016 nails were analyzed (517 from patients with psoriatic arthritis and 499 from controls). Ultrasonography of the nails of the 10 fingers was performed to assess the trilaminar appearance, measure the distance from the nail bed, identify synovitis of the distal interphalangeal joints and the presence of a power Doppler signal from the nail matrix/nail bed. The captured images were independently evaluated by a rheumatologist with expertise in musculoskeletal ultrasound. Data analysis was performed using IBM SPSS Statistics v.28.0.0 software, and the association of nail plate changes, nail bed distance and power Doppler signal with the NAPSI, DAPSA, MDA and ASDAS-PCR were calculated. Spearman correlation coefficients were estimated to analyze the correlations between pairs of quantitative variables. Student's t test and the Mann‒Whitney U test were used to compare quantitative variables, and Fisher's exact test was used to compare categorical variables between patients and controls. The nonparametric Mann‒Whitney U and Kruskal‒Wallis tests were used to compare groups according to the MDA or DAPSA classification., Results: The Doppler signal of the nail matrix and nail bed was more frequently identified in patients (44.2%) than in controls (6%), and the difference in the mean power Doppler signal between the two groups was significant (p < 0.001). Changes in the nail plate were more common in the right thumb (44.2%), left thumb (36.5%) and second finger on the right hand (32.7%). The number of fingers with nail plate changes, enthesitis, paratendinitis, grayscale synovitis and DIP involvement in the distal interphalangeal joints was higher among patients with psoriatic arthritis (p < 0.001). There were found some correlations between US findings and clinical scores: ultrasound nail involvement and the NAPSI score (p = 0.034), the number of fingers and mean change in the nail plate and the ASDAS-CRP (p = 0.030). DAPSA (remission/low activity versus moderate/high activity) was associated to the mean change in the nail plate (p < 0.013)., Conclusions: Nail ultrasound has the potential to assist in the capturing of the actual disease activity status in patients with psoriatic arthritis., (© 2024. The Author(s).)

Although the terms "rare diseases" (RD) and "orphan diseases" (OD) are often used interchangeably, specific nuances in definitions should be noted to avoid misconception. RD are characterized by a low prevalence within the population, whereas OD are those inadequately recognized or even neglected by the medical community and drug companies. Despite their rarity, as our ability on discovering novel clinical phenotypes and improving diagnostic tools expand, RD will continue posing a real challenge for rheumatologists. Over the last decade, there has been a growing interest on elucidating mechanisms of rare autoimmune and autoinflammatory rheumatic diseases, allowing a better understanding of the role played by immune dysregulation on granulomatous, histiocytic, and hypereosinophilic disorders, just to name a few. This initiative enabled the rise of innovative targeted therapies for rheumatic RD. In this review, we explore the state-of-the art of rare RD and the critical role played by rheumatologists in healthcare. We also describe the challenges rheumatologists may face in the coming decades., (© 2024. The Author(s).)

Amyloidosis is a localized or systemic disease caused by deposition of proteins in the extracellular space of various organs and tissues. As part of the disease, proteins that were originally soluble misfold and acquire a fibrillar conformation that renders them insoluble and resistant to proteolysis. Systemic amyloidosis is a rare, often underdiagnosed condition. In recent years, the incidence of newly diagnosed cases of amyloidosis has been increasing in association with the aging of the population and greater access to diagnostic tests. From a clinical perspective, systemic amyloidosis is frequently associated with involvement of the kidneys (causing nephrotic syndrome), heart (cardiac failure and arrhythmia), and peripheral nervous system (sensorimotor polyneuropathy and autonomic dysfunction). This condition is important to the rheumatologist for several reasons, such as its systemic involvement that mimics autoimmune rheumatic diseases, its musculoskeletal manifestations, which when recognized can allow the diagnosis of amyloidosis, and also because reactive or secondary AA amyloidosis is a complication of rheumatic inflammatory diseases. The treatment of amyloidosis depends on the type of amyloid protein involved. Early recognition of this rare disease is fundamental for improved clinical outcomes., (© 2024. The Author(s).)

Background: Spondyloarthritis (SpA) encompasses a spectrum of immune-mediated inflammatory conditions primarily affecting the axial skeleton, including sacroiliitis and spondylitis, each with distinct features. This study aimed to investigate imaging disparities, focusing on sacroiliac magnetic resonance and spine radiography, across phenotypes and between males and females in axial SpA., Method: A cross-sectional study was conducted to assess clinical data, laboratory findings, magnetic resonance imaging (MRI) scores of sacroiliac joints using the Spondyloarthritis Research Consortium of Canada (SPARCC) and Sacroiliac Joint Structural Score (SSS), and cervical and lumbar spine radiographs utilizing the Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The study aimed to compare these parameters between two groups: axial spondyloarthritis (axSpA, radiographic and non-radiographic) and axial psoriatic arthritis (axPsA), as well as between males and females., Results: Ninety-four patients were included, with 62 patients in the axSpA group and 32 patients in the axPsA group. There were no differences in disease activity, mobility, radiographic damage in the spine (Modified Stoke Ankylosing Spondylitis Spine Score- mSASSS), or sacroiliac magnetic resonance imaging (MRI) scores (Spondyloarthritis Research Consortium of Canada Magnetic Resonance Imaging Index - SPARCC and Sacroiliac Joint Structural Score - SSS) between the two phenotypes. Regarding sex, in imaging exams, men had higher mSASSS (p = 0.008), SSS (p = 0.001), and fat metaplasia (MG) score based on SSS (p = 0.001), while women had significantly higher SPARCC scores (p = 0.039). In the male group, the presence of HLA-B27 allele had an impact on more structural lesions on MRI (SSS), p = 0.013., Conclusion: In this study, imaging of sacroiliac joints and spine in patients with axial SpA did not show differences in phenotypes but did reveal differences based on sex, which may have an impact on future diagnostic recommendations. Further studies are needed to confirm these findings., (© 2024. The Author(s).)

Background: Biosimilars offer significant advantages for improving access to biologic treatments in Latin America. However, their uptake has been slow due to misconceptions, regulatory uncertainties, and inadequate pharmacovigilance., Objective: To address these issues, Americas Health Foundation convened a multidisciplinary panel of regional experts in biosimilar use and interchangeability from Latin America. The panel assessed the current landscape and recommended steps to enhance access., Results: Key recommendations include strengthening biosimilar regulations, ensuring transparent enforcement, implementing robust pharmacovigilance, and promoting collaboration among stakeholders to educate about the safety, efficacy, and economic advantages of biosimilars and their interchangeability., Conclusions: By embracing biosimilars and interchangeability, Latin American countries can expand patient access, foster competition, diversify treatment sources, and enhance the sustainability of their healthcare systems. However, achieving these goals requires addressing knowledge gaps and biases among healthcare providers, patients, regulators, and government agencies. This can be accomplished through clear communication and the use of real-world evidence., (© 2024. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Background: Patients with immune-mediated rheumatic diseases (IMRDs) have been prioritized for COVID-19 vaccination to mitigate the infection severity risks. Patients with rheumatoid arthritis (RA) are at a high risk of severe COVID-19 outcomes, especially those under immunosuppression or with associated comorbidities. However, few studies have assessed the safety of the COVID-19 vaccine in patients with RA., Objective: To evaluate the safety of vaccines against SARS-CoV-2 in patients with RA., Methods: This data are from the study "Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases," a Brazilian multicentric prospective phase IV study to evaluate COVID-19 vaccine in IMRDs in Brazil. Adverse events (AEs) in patients with RA of all centers were assessed after two doses of ChAdOx1 (Oxford/AstraZeneca) or CoronaVac (Sinovac/Butantan). Stratification of postvaccination AEs was performed using a diary, filled out daily and returned at the end of 28 days for each dose., Results: A total of 188 patients with RA were include, 90% female. CoronaVac was used in 109 patients and ChAdOx1 in 79. Only mild AEs were observed, mainly after the first dose. The most common AEs after the first dose were pain at the injection (46,7%), headache (39,4%), arthralgia (39,4%), myalgia (30,5%) and fatigue (26,6%), and ChAdOx1 had a higher frequency of pain at the injection (66% vs 32 %, p < 0.001) arthralgia (62% vs 22%, p < 0.001) and myalgia (45% vs 20%, p < 0.001) compared to CoronaVac. The more common AEs after the second dose were pain at the injection (37%), arthralgia (31%), myalgia (23%), headache (21%) and fatigue (18%). Arthralgia (41,4% vs 25%, p = 0.02) and pain at injection (51,4% vs 27%, p = 0.001) were more common with ChAdOx1. No serious AEs were related. With Regard to RA activity level, no significant difference was observed between the three time periods for both COVID-19 vaccines., Conclusion: In the comparison between the two immunizers in patients with RA, local reactions and musculoskeletal symptoms were more frequent with ChAdOx1 than with CoronaVac, especially after the first dose. In summary, the AE occurred mainly after the first dose, and were mild, like previous data from others immunizing agents in patients with rheumatoid arthritis. Vaccination did not worsen the degree of disease activity., (© 2024. The Author(s).)

Introduction: This integrated analysis of the phase 2/3 and phase 3 SELECT trials describes the safety profile of upadacitinib, an oral Janus kinase inhibitor, for up to 5 years of exposure across psoriatic arthritis (PsA), ankylosing spondylitis (AS), and non-radiographic axial spondyloarthritis (nr-axSpA) (including pooled axial spondyloarthritis [axSpA])., Methods: Safety data from five trials of upadacitinib in PsA (2 trials), AS (2 trials), and nr-axSpA (1 trial) were analyzed up to a data cut-off of August 15, 2022. One PsA study included adalimumab as an active comparator. Treatment-emergent adverse events (TEAEs) were summarized for PsA (pooled upadacitinib 15 mg once daily and adalimumab 40 mg biweekly), AS (pooled upadacitinib 15 mg), nr-axSpA (upadacitinib 15 mg), and pooled axSpA (pooled upadacitinib 15 mg from axSpA trials). TEAEs were reported as exposure-adjusted event rates per 100 patient-years (E/100 PY)., Results: A total of 1789 patients (PsA, n = 907; AS, n = 596; nr-axSpA, n = 286) received ≥ 1 dose of upadacitinib 15 mg for 3689 PY of exposure or adalimumab (n = 429) for 1147 PY of exposure. Overall TEAEs and serious TEAEs were highest in PsA and numerically higher with upadacitinib versus adalimumab; rates were similar between AS and nr-axSpA. In PsA, higher rates of serious infection, herpes zoster (HZ), lymphopenia, and nonmelanoma skin cancer (NMSC) were observed with upadacitinib versus adalimumab. Rates of malignancy excluding NMSC, adjudicated major adverse cardiovascular events, and adjudicated venous thromboembolic events were comparable between upadacitinib and adalimumab in PsA and were similar across diseases., Conclusion: Higher rates of serious infection, HZ, lymphopenia, and NMSC were observed with upadacitinib versus adalimumab in PsA; slightly elevated rates for most of these TEAEs were seen with upadacitinib in PsA versus axSpA. Upadacitinib 15 mg demonstrated a generally consistent safety profile across disease states with no new safety signals identified., Trial Registration: SELECT-AXIS 1: NCT03178487; SELECT-AXIS 2: NCT04169373; SELECT-PsA 1: NCT03104400; SELECT-PsA 2: NCT03104374., (© 2024. The Author(s).)

Hereditary connective tissue disorders include more than 200 conditions affecting different organs and tissues, compromising the biological role of the extracellular matrix through interference in the synthesis, development, or secretion of collagen and/or its associated proteins. The clinical phenotype includes multiple signs and symptoms, usually nonspecific but of interest to rheumatologists because of musculoskeletal involvement. The patient´s journey to diagnosis is long, and physicians should include these disorders in their differential diagnoses of diseases with systemic involvement. In this review, insights for the diagnosis and treatment of osteogenesis imperfecta, hypermobility spectrum disorder/Ehlers-Danlos syndrome, Marfan, Loeys-Dietz, and Stickler syndromes are presented., (© 2024. The Author(s).)

Introduction/objectives: Psoriatic arthritis (PsA) is a chronic multisystem osteoarticular disease that requires specialized care. Most Brazilians depend on the public healthcare provided by the Unified Health System (Sistema Único de Saúde, SUS). This study aimed to describe the epidemiological characteristics of patients with PsA in follow-up in SUS, focusing on the incidence and prevalence of the disease, comorbidities, and hospitalizations., Methods: We collected data from the Outpatient Data System of SUS (Sistema de Informações Ambulatoriais do SUS, SIA/SUS) regarding outpatient visits and hospitalizations in the Brazilian public healthcare system from January 2008 to March 2021 using the Techtrials Disease Explorer® platform and the medical code related to PsA were selected., Results: We evaluated 40,009 patients and found a prevalence of 24.4 cases of visits due to PsA per 100,000 patients in follow-up in SUS. Female patients were predominant (54.38%). The incidence of visits due to PsA has been increasing in recent years and we observed an incidence of 8,982 new visits in 2020. The main comorbidities of these patients were osteoarthritis, lower back pain, shoulder injuries, oncological diseases, crystal arthropathies, and osteoporosis. Hospitalizations were mainly due to treating clinical or cardiovascular conditions and performing orthopedic procedures., Conclusion: The number of visits due to PsA in SUS has increased in recent years, mainly on account of new diagnoses of the disease, although the prevalence found in this study's population was lower than that observed in the general population., (© 2023. Sociedade Brasileira de Reumatologia.)

Introduction: To compare perceptions of disease control and treatment satisfaction between patients with psoriatic arthritis (PsA) in North America and Europe, and between participating countries within each region., Methods: Data were collected from patients with self-reported PsA diagnoses using an online survey. Results from questions on perceptions of overall health, disease severity, PsA symptoms, PsA impacts, and treatment satisfaction/preferences were reported using descriptive statistics and Chi-square tests., Results: A total of 456 patients from North America (Canada, n = 155; US, n = 301) and 417 patients from Europe (France, n = 123; Spain, n = 135; UK, n = 159) were included in this analysis. Patients in North America were more likely to rate their overall health as excellent/good compared with those in Europe (49 vs. 14%), but also rate their disease as severe (27 vs. 15%). Despite treatment, patients in North America and Europe still experienced musculoskeletal (92 vs. 91%) and skin/nail (62 vs. 58%) symptoms. Similar proportions of patients in North America vs. Europe experienced a social impact (81 vs. 85%); more patients in Europe vs. North America experienced PsA-related work impacts (83 vs. 74%). Satisfaction with PsA medication was more common in North America (89%) vs. Europe (79%), and more common in Spain (91%) vs. the UK (82%) or France (66%). Across all regions and countries, ≥ 75% of patients agreed that symptoms were controlled. However, ≥ 66% wished they had more medication choices, and ≥ 84% wanted to change something about their medication., Conclusions: Although perception of overall health and disease severity varied, many patients from both regions still experienced symptoms despite receiving medications for PsA, wished they had greater choice of medications, and/or would like to change an aspect of their medications. While these survey findings are subject to selection bias, they do indicate there is scope to improve the treatment of PsA., (© 2022. The Author(s).)

The pathogenesis of psoriasis, an immune-mediated chronic inflammatory skin disease, remains unclear. Studies have shown an association between psoriasis and intestinal inflammation; in this context, the influence of the gut microbiota on the immune response of psoriasis has become a focus of recent research. The present research evaluated the composition and diversity of the gut microbiota of 21 participants with psoriasis from a Brazilian referral dermatology service compared to 24 healthy controls. A stool sample was collected from each participant at the time of inclusion in the study, and the samples were analysed by sequencing the 16S rRNA gene. The recruitment of research participants involved matching between groups by sex, age, body mass index, comorbidities and smoking and the exclusion of several criteria that could potentially influence the gut microbiota and the interpretation of the data. There was an increase in the Dialister genus and Prevotella copri species in patients with psoriasis compared to the control group. A reduction in the Ruminococcus, Lachnospira and Blautia genera, as well as in the Akkermansia muciniphila species, was also verified in the psoriasis group compared to the control group. Furthermore, patients with psoriasis exhibited less gut microbiota diversity than controls., (© 2021 The Society for Applied Microbiology.)

Introduction: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA). This post hoc analysis assessed frequency or duration of early select non-serious adverse events (AEs; excluding infections), and their impact on treatment discontinuation, in patients with RA or PsA treated with tofacitinib 5 or 10 mg twice daily, or placebo., Methods: Data were pooled from five phase 3 and one phase 3b/4 studies in patients with moderate-to-severe RA, and two phase 3 studies in patients with active PsA. Select all-causality, non-serious AEs, reported to month 3 (placebo-controlled period), were headache, diarrhea, nausea, vomiting, and gastric discomfort (including dyspepsia, gastritis, epigastric discomfort, and abdominal discomfort or pain); incidence rates (unique patients with events per 100 patient-years of follow-up), duration of, and discontinuations due to these non-serious AEs were reported., Results: We analyzed 3871 and 710 patients with RA and PsA, respectively. Incidence of non-serious AEs to month 3 was generally similar with tofacitinib and placebo. The most frequent non-serious AEs were headache and diarrhea with tofacitinib, and dyspepsia, nausea, and headache with placebo. Most events were mild or moderate in severity, lasting ≤ 4 weeks. Permanent discontinuations due to non-serious AEs were not observed in patients with PsA, and were < 1.0% in patients with RA across treatment groups. The most frequent cause of temporary discontinuation across all groups was gastric discomfort (0.3-0.8%)., Conclusions: Non-serious AE incidence was generally similar in patients with RA or PsA receiving tofacitinib or placebo. Most events were mild or moderate and generally resolved within 4 weeks., Trial Registration: ClinicalTrials.gov identifiers: NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01877668; NCT01882439; NCT02187055., (© 2021. The Author(s).)

Introduction: This integrated analysis describes the safety profile of upadacitinib, an oral Janus kinase inhibitor, at 15 and 30 mg once daily for up to 3 years of exposure in patients with active psoriatic arthritis (PsA) who had a prior inadequate response or intolerance to ≥ 1 non-biologic or biologic disease-modifying antirheumatic drug., Methods: Safety data were pooled and analyzed from two randomized, placebo-controlled phase 3 trials. Both trials evaluated upadacitinib 15 mg and 30 mg once daily, and one trial also evaluated adalimumab 40 mg every other week. Treatment-emergent adverse events (TEAEs) and laboratory data were summarized for four groups: pooled placebo, pooled upadacitinib 15 mg, pooled upadacitinib 30 mg, and adalimumab. TEAEs were reported as exposure-adjusted event rates (events per 100 patient-years [E/100 PY]) up to a data cut-off of June 29, 2020., Results: A total of 2257 patients received ≥ 1 dose of upadacitinib 15 mg (N = 907) or 30 mg (N = 921) for 2504.6 PY of exposure or adalimumab (N = 429) for 549.7 PY of exposure. Upper respiratory tract infection, nasopharyngitis, and increased creatine phosphokinase (CPK) were the most common TEAEs with upadacitinib. Rates of malignancies, adjudicated major adverse cardiovascular events (MACEs) and venous thromboembolic events (VTEs), and deaths were similar across treatment groups. Rates of herpes zoster (HZ) and opportunistic infections (OI; excluding tuberculosis, HZ, and oral candidiasis) were higher with upadacitinib versus adalimumab. Serious infection, anemia, and CPK elevations were most frequent with upadacitinib 30 mg. Potentially clinically significant laboratory abnormalities were uncommon., Conclusions: Upadacitinib 15 mg and adalimumab had similar safety profiles with the exception of HZ and OIs, consistent with what was observed in rheumatoid arthritis. Rates of malignancies, MACEs, VTEs, and deaths were comparable among patients receiving upadacitinib and adalimumab. No new safety risks emerged with longer-term exposure to upadacitinib., Trial Registration Numbers: SELECT-PsA 1: NCT03104400; SELECT-PsA 2: NCT03104374., (© 2021. The Author(s).)

Extraintestinal manifestations occur frequently in patients with inflammatory bowel disease (IBD) and remain a diagnostic and therapeutic challenge. The aim of the Endpoints for Extraintestinal Manifestations in Inflammatory Bowel Disease Trials (EXTRA) initiative was to achieve international expert consensus on how to assess these manifestations in IBD trials. A systematic literature review was done to identify methods to diagnose extraintestinal manifestations in patients with IBD and measure treatment outcomes. A consensus meeting involving a panel of 41 attendees, including gastroenterologists and referral specialists, was held on March 31, 2021, as part of an International Organization for the Study of Inflammatory Bowel Diseases initiative. The panel agreed that a specialist's expertise is needed to confirm the diagnosis of extraintestinal manifestations before the inclusion of a patient in IBD trials, except for axial spondyloarthritis, for which typical symptoms and MRI can be sufficient. Easy-to-measure endpoints were identified to assess the response of extraintestinal manifestations to treatment without needing specialist involvement. For uveitis, peripheral spondyloarthritis, and arthralgia, endpoint measurements need specialist expertise. The timing of endpoint measurements was discussed for individual extraintestinal manifestations. The EXTRA consensus proposes guidelines on how to thoroughly evaluate extraintestinal manifestations within IBD trials, and recommends that these guidelines are implemented in future trials to enable prospective assessment of these manifestations and comparison between studies., Competing Interests: Declaration of interests LGu reports consulting fees from AbbVie. RP reports consulting fees from AbbVie, Abbott, Alimentiv (formerly Robarts Clinical Trials), Amgen, Arena Pharmaceuticals, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Mylan, Oppilan Pandion, Pharma, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Satisfai Health, Sandoz, Schering-Plough, Shire, Sublimity Therapeutics, Theravance Biopharma, Union Chimique Belge, and Takeda Pharmaceuticals; and research support from AbbVie, Ferring, Janssen, Pfizer, and Takeda. WJS reports research grants from AbbVie, Abivax, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Pfizer, Prometheus Biosciences, Seres Therapeutics, Shire, Takeda, and Theravance Biopharma; consulting fees from AbbVie, Abivax, Admirx, Alfasigma, Alimentiv Alivio Therapeutics, Allakos, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, Bausch Health (Salix), Beigene, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Celgene, Celltrion, Cellularity, Cosmo Pharmaceuticals, Escalier Biosciences, Equillium, Forbion, Genentech/Roche, Gilead Sciences, Glenmark Pharmaceuticals, Gossamer Bio, Immunic (Vital Therapies), Index Pharmaceuticals, Intact Therapeutics, Janssen, Kyverna Therapeutics, Landos Biopharma, Lilly, Oppilan Pharma, Otsuka, Pandion Therapeutics, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonists Therapeutics, Provention Bio, Reistone Biopharma, Seres Therapeutics, Shanghai Pharma Biotherapeutics, Shire, Shoreline Biosciences, Sublimity Therapeutics, Surrozen, Takeda, Theravance Biopharma, Thetis Pharmaceuticals, Tillotts Pharma, UCB, Vendata Biosciences, Ventyx Biosciences, Vimalan Biosciences, Vivelix Pharmaceuticals, Vivreon Biosciences, and Zealand Pharma; and stock or stock options from Allakos, BeiGene, Gossamer Bio, Oppilan Pharma, Prometheus Biosciences, Prometheus Laboratories, Progenity, Shoreline Biosciences, Ventyx Biosciences, Vimalan Biosciences, and Vivreon Biosciences. MAl has served as a speaker, consultant, and advisory board member for Amgen, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Genentech IQVIA, Janssen, Novartis, Pfizer, Roche, Takeda, and Tillotts. ANA has served as an advisory board member for AbbVie, Gilead Sciences, Sun Pharma, and Ikena Therapeutics, and is supported by research funding from the Chleck Family Foundation, Crohn's and Colitis Foundation, and the National Institutes of Health. PGK reports speaking and consultancy honoraria from AbbVie, Janssen, Ferring, Pfizer, Takeda, and Novartis, and scientific grants from Pfizer and Takeda. IEK has served as an advisory board member for AbbVie, Astelas, Genesis, Janssen, Merck Sharp & Dohme, Pharmacosmos, Pfizer, Shire, and Takeda; as a speaker for AbbVie, Astelas, Genesis, Janssen, Merck Sharp & Dohme, and Takeda; and has received research support from AbbVie, Ferring, and Vifor Pharma. PLL has served as a speaker and advisory board member for AbbVie, Amgen, Arena Pharmaceuticals, Fresenius Kabi, Genetech, Gilead Sciences, Janssen, Merck, Mylan, Pharmacosmos, Pfizer, Roche, Takeda, Tillots, and Viatris; and has received unrestricted research grants from AbbVie, Takeda, and Pfizer. JOL reports honoraria for developing and delivering the Cornerstones Health Best of DDW program; funding from AbbVie, Celgene, Gilead Sciences, Janssen, Pfizer, Takeda, and Tillots; additional research support from AbbVie, Gilead Sciences, Pfizer, Shire, and Takeda; consultancy fees from AbbVie, Allergan (Warner Chilcott), Atlantic Healthcare, Bristol Myers Squibb, Celgene, Celtrion, Ferring, Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Merck Sharp & Dohme, Napp, Norgine, Pfizer, Shire, Takeda, and Vifor Pharma, and speaking fees and travel support from AbbVie, Allergan (Warner Chilcott), Ferring, Janssen, Merck Sharp & Dohme, Napp, Norgine, Pfizer, Shire, Tillotts, and Takeda. FM has served as a speaker for, and has received honoraria from, AbbVie, Biogen, Falk, Ferring, Hospira, Janssen, Laboratorios Vitoria, Lilly, Merck Sharp & Dohme, Pfizer, Takeda, Sandoz, UCB, and Vifor Pharma. GJM has served as advisory board member for AbbVie, Celgene, Celtrion, Ferring, Genesis, Hospira, Janssen, Millennium Pharmaceuticals, Merck Sharp & Dohme, Mylan, Pharmacosmos, Pfizer, Takeda, and Vianex; has served as a speaker for AbbVie, Angelini, Falk Pharma, Ferring, Galenica, Cenesis, Hospira, Janssen, Merck Sharp & Dohme, Omega Pharma, Takeda, and Vianex; has served as a consultant for Merck Sharp & Dohme and Takeda; and has received research support from AbbVie, Galenica, Genesis, Menarini Group, and Merck Sharp & Dohme. SCN reports research grants and speaker honoraria from Takeda, Ferring, AbbVie, Janssen, and Tillotts. JP has received research grants from AbbVie and Pfizer; speaker's fees from AbbVie, Ferring, Janssen, Pfizer, and Takeda; and has been a consultant for AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Genentech, GlaxoSmithKline, Janssen, Origo, Pandion, Pfizer, Progenity, Alimentiv (formerly Robarts Clinical Trials), Roche, Takeda, Theravance, and Wassermann. GR has consulted for AbbVie, Augurix, Bristol Myers Squibb, Boehringer, Calypso, Celgene, Falk, Ferring, Fisher, Genentech, Gilead Sciences, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Phadia, Roche, UCB, Takeda, Tillotts, Vifor Pharma, Vital Solutions, and Zeller; has received speaker's honoraria from AstraZeneca, AbbVie, Falk, Janssen, Merck Sharp & Dohme, Pfizer, Phadia, Takeda, Tillotts, UCB, Vifor Pharma, and Zeller; and has received educational grants and research grants from AbbVie, Ardeypharm, Augurix, Calypso, FALK, Flamentera, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, Tillotts, UCB, and Zeller. FS has served as a speaker and consultant for AbbVie, Amgen, Ferring, Janssen, Pfizer, Sandoz, Takeda, and UCB. AD has served as a speaker, consultant, and advisory board member for Merck Sharp & Dohme, AbbVie, Janssen, Roche/Genentech, Ferring, Tillotts, Vifor Pharma, Pharmacosmos, Pfizer, Celltrion, Takeda, Boehringer Ingelheim, Amgen, Sandoz, Bristol Myers Squibb/Celgene, Otsuka, Biogen, Gilead/Galapagos, Fresenius Kabi, and Arena Pharmaceuticals. BES reports consulting fees from 4D Pharma, AbbVie, Allergan, Amgen, Arena Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Boston Pharmaceuticals, Capella Biosciences, Celgene, Celltrion Healthcare, EnGene, Ferring, Genentech, Gilead Sciences, Hoffmann-La Roche, Immunic, Ironwood Pharmaceuticals, Janssen, Lilly, Lyndra, MedImmune, Morphic Therapeutic, Oppilan Pharma, OSE Immunotherapeutics, Otsuka, Palatin Technologies, Pfizer, Progenity, Prometheus Laboratories, RedHill Biopharma, Rheos Medicines, Seres Therapeutics, Shire, Synergy Pharmaceuticals, Takeda, Target PharmaSolutions, Theravance Biopharma R&D, TiGenix, and Vivelix Pharmaceuticals; honoraria for speaking in continuing medical education programmes from Takeda, Janssen, Lilly, Gilead Sciences, Pfizer, and Genentech; and research funding from Celgene, Pfizer, Takeda, Theravance Biopharma R&D, and Janssen. SD has served as a speaker, consultant, and advisory board member for Schering-Plough, Abbott (AbbVie) Laboratories, Merck & Co, UCB Pharma, Ferring, Cellerix, Millennium Takeda, Nycomed, Pharmacosmos, Actelion, A Wasserman, Genentech, Grunenthal, Pfizer, AstraZeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor Pharma, and Johnson & Johnson. LP-B has served as a speaker, consultant, and advisory board member for Merck, AbbVie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillotts, Vifor Pharma, Hospira/Pfizer, Celltrion, Takeda, Biogaran, Boehringer Ingelheim, Lilly, HAC Pharma, Index Pharmaceuticals, Amgen, Sandoz, Forward Pharma, Celgene, Biogen, Lycera, Samsung Bioepis, and Theravance. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Analyze tofacitinib efficacy and safety by background methotrexate (MTX) dose in patients with psoriatic arthritis (PsA)., Methods: This post hoc analysis pooled data from two phase III, double-blind trials (OPAL Broaden, NCT01877668; OPAL Beyond, NCT01882439) including patients receiving tofacitinib 5 or 10 mg twice daily (BID), or placebo, with stable MTX. Efficacy outcomes at month 3 stratified by MTX dose (≤ 15 month 3 stratified by MTX dose vs > 15 mg/week) were American College of Rheumatology (ACR)20/50/70, Health Assessment Questionnaire-Disability Index (HAQ-DI); Psoriasis Area and Severity Index (PASI)50/75; change from baseline in HAQ-DI; physician's global assessment of PsA (PGA-PsA-visual analog scale [VAS]); patient's global joint and skin assessment (PGJS-VAS), Leeds Enthesitis Index (LEI); and Dactylitis Severity Score (DSS). Safety assessments included adverse events and laboratory parameters., Results: Five hundred fifty-six patients received tofacitinib 5 mg BID (n = 186), 10 mg BID (n = 178), or placebo (n = 192), plus MTX (≤ 15 mg/week, n = 371; > 15 mg/week, n = 185). At month 3, tofacitinib efficacy was generally greater than placebo. Patients receiving tofacitinib 5 mg BID demonstrated greater numerical improvements in efficacy outcomes at month 3 with MTX > 15 mg/week vs MTX ≤ 15 mg/week; patients receiving tofacitinib 10 mg BID displayed the opposite. The safety profile was generally consistent between groups; headache was associated with MTX > 15 mg/week; decreased hemoglobin levels were observed in patients receiving tofacitinib 10 mg BID and MTX ≤ 15 mg/week., Conclusion: Efficacy of tofacitinib was generally numerically greater than placebo, regardless of MTX dose. Tofacitinib 5 mg BID was generally more efficacious with MTX > 15 mg/week vs ≤ 15 mg/week; the opposite was observed for tofacitinib 10 mg BID. Headache was more frequent with MTX > 15 mg/week., Trial Registration: ClinicalTrials.gov . Identifier: NCT01877668 (registration: June 14, 2013) and NCT01882439 (registration: June 20, 2013). Key Points • Methotrexate is widely used in the treatment of psoriatic arthritis; however, there are limited data on the impact of varying background methotrexate doses on the efficacy and safety of Janus kinase inhibitors in patients with psoriatic arthritis. • This post hoc analysis assessed the impact of background methotrexate dose (≤ 15 or > 15 mg/week) on tofacitinib efficacy and safety in patients with psoriatic arthritis. • Results indicated that tofacitinib efficacy was generally numerically greater than placebo, regardless of methotrexate dose. Tofacitinib 5 mg twice daily, in combination with a higher dose of background methotrexate, was more efficacious compared with a lower dose of background methotrexate; the opposite was observed for tofacitinib 10 mg twice daily. • Headache was more frequent with the higher methotrexate dose. Data should be interpreted with caution due to the small sample sizes., (© 2021. The Author(s).)

The risk of herpes zoster (HZ) and HZ-related complications is increased in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) relative to the general population; therefore, HZ vaccination is recommended in these patient groups. In this literature-based review, we summarise the available evidence on the use of HZ vaccines in patients with RA and PsA, and discuss strategies for managing breakthrough infection. Currently available data show suboptimal rates of HZ vaccination among these patients and highlight a need for strategies to improve HZ vaccination programmes in clinical practice. Further clinical studies are also required to optimise the use of HZ vaccines in patients with RA and PsA, particularly with regard to determining the impact of different immunosuppressive therapy regimens on vaccine immunogenicity and, ultimately, efficacy, as well as the impact of vaccination on disease activity and safety.

Introduction: Effective communication between patients with psoriatic arthritis (PsA) and their physicians is important for optimizing treatment outcomes. We assessed the quality of patient-physician communication in terms of awareness and impact of PsA symptoms, their levels of satisfaction, and their perceptions of communications., Methods: A global online survey was conducted by The Harris Poll in adult patients with PsA and physicians managing patients with PsA in eight countries. Participating physicians were either rheumatologists or dermatologists seeing ≥ 10 and ≥ 5 patients with PsA per month, respectively. Patient and physician groups were unmatched. Patient-physician communication was assessed with 35-60 questions regarding discussion topics during consultations, levels of satisfaction with communication, and specific communication issues., Results: A total of 1286 patients with PsA (983 and 303 whose primary treating physician was a rheumatologist or dermatologist, respectively) and 1553 physicians (795 rheumatologists and 758 dermatologists) completed the survey. Regardless of whether they were primarily treated by a rheumatologist or dermatologist, most patients reported a social (84% and 81%, respectively) or work (81% and 80%, respectively) impact of PsA, and a major/moderate negative impact on their physical activity levels (79% and 74%, respectively) or emotional/mental wellbeing (69% and 68%, respectively). Physician responses were generally consistent with this; however, physicians often appeared to under-recognize the extent to which PsA affects patients. Most (≥ 85%) patients and physicians were very/somewhat satisfied with their patient-physician communication, and most (≥ 86%) patients were comfortable raising their concerns/fears with their physician. However, > 40% of patients were identified as being at risk of suboptimal communication. These patients were significantly less likely to report their PsA symptoms even when asked, were less comfortable discussing the impacts of PsA with their physician, and were more likely to experience major/moderate impacts of PsA on their health-related quality of life (HRQoL)., Conclusions: Physicians often underestimate the impacts of PsA, compared with patients, and some patients may be at risk of suboptimal communication with their attending physician, which may worsen the HRQoL impacts of PsA. These findings highlight a need for ways to improve communication between patients with PsA and their healthcare providers., (© 2021. The Author(s).)

Psoriatic arthritis (PsA) is a chronic and systemic immune disease characterized by inflammation of peripheral and/or axial joints and entheses in patients with psoriasis (PsO). Extra-articular and extracutaneous manifestations and numerous comorbidities can also be present. These recommendations replace the previous version published in May 2013. A systematic review of the literature retrieved 191 articles that were used to formulate 12 recommendations in response to 12 clinical questions, divided into 4 sections: diagnosis, non-pharmacological treatment, conventional drug therapy and biologic therapy. These guidelines provide evidence-based information on the clinical management for PsA patients. For each recommendation, the level of evidence (highest available), degree of strength (Oxford) and degree of expert agreement (interrater reliability) are reported., (© 2021. The Author(s).)

Over time, clinicians have become increasingly comfortable embracing the prescription of biosimilars-highly similar versions of innovator or reference biological agents-for their patients with inflammatory diseases. Although a switch from a reference product to a licensed biosimilar version (or vice versa) is a medical decision robustly supported by the stepwise accumulation of clinical trial evidence concerning comparable safety, immunogenicity, and efficacy between these products, a switch from one biosimilar to another biosimilar of the same reference product, or a cross-switch, is not. Similarity among biosimilars of a reference product is not a regulatory agency concern and therefore is unlikely to be investigated in randomized controlled trials in the foreseeable future. Yet in clinical practice, across a diverse range of patients, the option to cross-switch from one biosimilar to another can and does arise for valid reasons such as convenience or tolerability issues, or driven by third parties (e.g., payers). In the absence of clinical trial data, clinicians must attempt to objectively evaluate the emerging real-world cross-switching evidence within the context of what is known about the science underpinning a designation of biosimilar. That knowledge then needs to be integrated with what clinicians know about their patients and their disease on a case-by-case basis. This review aims to consolidate relevant emerging real-world data and other key information about biosimilar-to-biosimilar cross-switching for prescribing clinicians. In the absence of clear clinical guidelines addressing this topic at present, this review may serve to facilitate discretionary and educated treatment decision making., (© 2021. The Author(s).)

Purpose: The objective of this review is to address the barriers limiting access to diagnosis and treatment of systemic lupus erythematosus (SLE) and lupus nephritis (LN) in Brazil, specifically for patients in the public healthcare system, arguably those with the least access to innovation., Design: A selected panel of Brazilian experts in SLE/LN were provided with a series of relevant questions to address in a multi-day conference. During the conference, responses were discussed and edited by the entire group through numerous drafts and rounds of discussion until a consensus was achieved., Results: The authors propose specific and realistic recommendations for implementing access to innovative diagnostic tools and treatment alternatives for SLE/LN in Brazil. Moreover, in creating these recommendations, the authors strived to address barriers and impediments for technology adoption. The multidisciplinary care required for SLE/LN necessitates the collective participation of all involved stakeholders., Conclusion: A great need exists to expand the adoption of innovative diagnostic tools and treatments for SLE/LN not only in Brazil but also in most countries, as access issues remain an urgent demand. The recommendations presented in this article can serve as a strategy for new technology adoption in other countries in a similar situation.

Background: Coronavirus disease 2019 (COVID-19) fatality rate is high among kidney transplant recipients. Among survivors, kidney outcomes, seroconversion, and persistence of viral shedding are unexplored., Methods: Single-center prospective cohort study including data from kidney transplant recipients with confirmed COVID-19 between March 20, 2020 and July 31, 2020. Outcomes were adjudicated until August 31, 2020 or the date of death., Results: There were 491 patients with COVID-19 among the 11 875 recipients in follow-up. The majority were middle aged with ≥1 comorbidities. Thirty-one percent were treated at home, and 69% required hospitalization. Among the hospitalized, 61% needed intensive care, 75% presented allograft dysfunction, and 46% needed dialysis. The overall 28-day fatality rate was 22% and among hospitalized patients it was 41%. Age (odds ratio, 3.08; 95% confidence interval, 1.86-5.09), diabetes mellitus (odds ratio, 1.69; 95% confidence interval, 1.06-2.72), and cardiac disease (odds ratio, 2.00; 95% confidence interval, 1.09-3.68) were independent factors for death. Among the 351 survivors, 19% sustained renal graft dysfunction, and there were 13 (4%) graft losses. Biopsy (n = 20) findings were diverse but decisive to guide treatment and estimate prognosis. Seroconversion was observed in 79% of the survivors and was associated with disease severity. Persistence of viral shedding was observed in 21% of the patients without detectable clinical implications., Conclusions: This prospective cohort analysis confirms the high 28-day fatality rate of COVID-19, associated primarily with age and comorbidities. The high incidence of allograft dysfunction was associated with a wide range of specific histologic lesions and high rates of sequelae and graft loss. Seroconversion was high and the persistence of viral shedding deserves further studies., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Spondyloarthritis (SpA) is a group of chronic inflammatory systemic diseases characterized by axial and/or peripheral joints inflammation, as well as extra-articular manifestations. Over some decades, nonsteroidal anti-inflammatory drugs (NSAIDs) have been the basis for the pharmacological treatment of patients with axial spondyloarthritis (axSpA). However, the emergence of the immunobiologic agents brought up the discussion about the role of NSAIDs in the management of these patients. The objective of this guideline is to provide recommendations for the use of NSAIDs for the treatment of axSpA. A panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis of randomized clinical trials for 15 predefined questions. The Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations were used, and at least 70% agreement of the voting panel was needed. Fourteen recommendations for the use of NSAIDs in the treatment of patients with axSpA were elaborated. The purpose of these recommendations is to support clinicians' decision making, without taking out his/her autonomy when prescribing for an individual patient.

Large epidemiologic and clinical estimates of spondyloarthritis (SpA) in Latin America are not available. In this narrative review, our goal was to descriptively summarize the prevalence and features of SpA in Latin America, based on available small studies. A review of peer-reviewed literature identified 41 relevant publications. Of these, 11 (mostly based on Mexican data) estimated the prevalence of SpA and its subtypes, which varied from 0.28 to 0.9% (SpA), 0.02 to 0.8% (ankylosing spondylitis), 0.2 to 0.9% (axial SpA), and 0.004 to 0.08% (psoriatic arthritis). Demographic and/or clinical characteristics were reported in 31 of the 41 publications, deriving data from 3 multinational studies, as well as individual studies from Argentina, Brazil, Chile, Colombia, Costa Rica, Mexico, Peru, Uruguay, and Venezuela. Data relating to treatment, disease manifestations (articular and extra-articular), and comorbidities were summarized across the countries. Available data suggest that there is a variability in prevalence, manifestations, and comorbidities of SpA across Latin America. Basic epidemiologic and clinical data are required from several countries not currently represented. Data relating to current treatment approaches, patient outcomes, and socioeconomic impact within this large geographic region are also needed.

Objectives: To evaluate risk factors associated with unfavourable outcomes: emergency care, hospitalisation, admission to intensive care unit (ICU), mechanical ventilation and death in patients with immune-mediated rheumatic disease (IMRD) and COVID-19., Methods: Analysis of the first 8 weeks of observational multicentre prospective cohort study (ReumaCoV Brasil register). Patients with IMRD and COVID-19 according to the Ministry of Health criteria were classified as eligible for the study., Results: 334 participants were enrolled, a majority of them women, with a median age of 45 years; systemic lupus erythematosus (32.9%) was the most frequent IMRD. Emergency care was required in 160 patients, 33.0% were hospitalised, 15.0% were admitted to the ICU and 10.5% underwent mechanical ventilation; 28 patients (8.4%) died. In the multivariate adjustment model for emergency care, diabetes (prevalence ratio, PR 1.38; 95% CI 1.11 to 1.73; p=0.004), kidney disease (PR 1.36; 95% CI 1.05 to 1.77; p=0.020), oral glucocorticoids (GC) (PR 1.49; 95% CI 1.21 to 1.85; p<0.001) and pulse therapy with methylprednisolone (PR 1.38; 95% CI 1.14 to 1.67; p=0.001) remained significant; for hospitalisation, age >50 years (PR 1.89; 95% CI 1.26 to 2.85; p=0.002), no use of tumour necrosis factor inhibitor (TNFi) (PR 2.51;95% CI 1.16 to 5.45; p=0.004) and methylprednisolone pulse therapy (PR 2.50; 95% CI 1.59 to 3.92; p<0.001); for ICU admission, oral GC (PR 2.24; 95% CI 1.36 to 3.71; p<0.001) and pulse therapy with methylprednisolone (PR 1.65; 95% CI 1.00 to 2.68; p<0.043); the two variables associated with death were pulse therapy with methylprednisolone or cyclophosphamide (PR 2.86; 95% CI 1.59 to 5.14; p<0.018)., Conclusions: Age >50 years and immunosuppression with GC and cyclophosphamide were associated with unfavourable outcomes of COVID-19. Treatment with TNFi may have been protective, perhaps leading to the COVID-19 inflammatory process., Competing Interests: Competing interests: CDLM reports grants from National Council for Scientific and Technological Development (CNPq) and from Brazilian Society of Rheumatology, personal fees from Janssen, Novartis, Abbvie. AMK reports personal fees from Abbvie, Janssen, Pfizer, Lilly and Roche. MMP reports personal fees from Abbvie, Janssen, UCB, Novartis, Pfizer and Lilly. LMHM reports personal fees from Abbvie, Janssen, Pfizer, Roche, Boehringer Ingelheim, GSK, Libbs and Lilly. CRS reports personal fees from Pfizer, Abbvie and Novartis. AD reports personal fees from Boehringer Ingelheim. RDG reports personal fees from Janssen, Eli Lilly, Roche, Boehringer Ingelheim, Amgen Brasil, Pfizer, Sandoz, Novartis Brasil. LDAV personal fees from Janssen, Novartis and UCB. AKGM reports grants from Brazilian Society of Rheumatology, personal fees from Janssen and UCB. MAY reports personal fees from Novartis, Abbvie, Lilly and, UCB. RAdT reports personal fees from ABBVIE, GSK, JANSSEN, NOVARTIS, LILLY, PFIZER, ROCHE and UCB. RX reports grants and personal fees from Abbvie, Eli-Lilly, Pfizer, Janssen and Roche, personal fees from Novartis, UCB., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The severity of nail disease, the presence of arthralgia and fatigue are predictors of development of psoriatic arthritis (PsA) in patients with psoriasis (Pso). In children, little is known about the musculoskeletal (MSK) impairment in patients with Pso and its effect on health-related quality of life (HRQoL)., Objectives: To determine the frequencies of pain and MSK inflammation (i.e., arthritis, enthesitis, and sacroiliitis) among children and adolescents with Pso and its relationship to HRQoL and fatigue., Methods: Pediatric patients with Pso underwent a rheumatologic physical examination to evaluate synovitis, enthesalgia, sacroiliac joint (SIJ) pain and tender points of fibromyalgia. The core set of domains recommended by the GRAPPA - OMERACT to be measured in PsA studies was assessed. Ultrasound (US) was performed in clinical cases of enthesitis, and magnetic resonance imaging (MRI) was performed in cases of SIJ pain., Results: Forty-three participants (10 ± 2.9 years old) were evaluated. Pain on palpation of the entheses was observed in 10 (23.2%) patients and pain on SIJ palpation was observed in 3 (7%). No patient presented with synovitis; one presented with enthesitis on US, but MRI did not confirm sacroiliitis in any case. Patients with MSK pain had greater skin disease severity (PASI 5.4 vs. 2, p <  0.01), worse fatigue, and lower HRQoL scores on all instruments used. The estimated risk of HRQoL impairment was eight times higher in the presence of MSK pain, which was an independent predictive factor. With a NAPSI greater than 30, the probability of pain was greater than 80%., Conclusion: MSK pain is frequent among children with Pso, related to the severity of skin and nail disease, and negatively affects HRQoL. The typically used complementary exams might not detect the inflammatory process caused by Pso.

Background: Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory musculoskeletal disease, manifesting as peripheral arthritis, enthesitis, dactylitis, spondylitis, and skin and nail psoriasis. A core set of domains for measuring the impact of PsA has been developed, including pain, patient global assessment, physical function, health-related quality of life (HRQoL), and fatigue. To understand the impact of PsA on health domains from a patient's perspective, a global survey was developed and results reported in the context of the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) questionnaire., Methods: An online patient-based global survey was conducted by The Harris Poll in Australia, Brazil, Canada, France, Spain, Taiwan, the UK, and the US between November 2, 2017 and March 12, 2018. Eligible patients were ≥ 18 years old with a diagnosis of PsA for > 1 year, had visited a rheumatologist/dermatologist in the past 12 months and reported using ≥ 1 synthetic/biologic disease-modifying antirheumatic drug for PsA. Patients reported on PsA severity and symptoms, and the impact of PsA on HRQoL. After survey completion, responses were aligned with PsAID health domains. Descriptive statistics and chi-square tests were conducted., Results: This analysis included 1286 patients from eight countries. Most patients (97%) reported musculoskeletal symptoms relating to PsA in the past year. Common moderate/major impacts of PsA were on physical activity (78%), ability to perform certain activities (76%), work productivity (62%), and career path (57%). Skin/nail symptoms occurred in 80% of patients. Overall, 69% of patients reported that PsA had a moderate/major impact on emotional/mental wellbeing, 56% on romantic relationships/intimacy, and 44% on relationships with family and friends. Social impacts included emotional distress (58%), social shame or disapproval (32%), and ceased participation in social activities (45%). Over half of all patients experienced unusual fatigue over the past 12 months (52%). The health domains that patients reported as being impacted by PsA aligned with life impact domains of the patient-derived PsAID health domains., Conclusion: These results highlight the impact of PsA on multiple health domains from a patient perspective that should be considered during shared decision-making processes between healthcare providers and patients.

Background: The inadequate storage of biopharmaceuticals may result in an ineffective therapeutic response since poor conservation can lead to the emergence of protein aggregates and cause immunogenicity in patients, which can increase the risk of adverse events by inducing the production of anti-drug antibodies. This can also lead to significant economic losses for public health, given the high cost of these medicines. The aim of this study was to verify whether the home storage of biopharmaceuticals dispensed by the Unified Public System was in accordance with the manufacturers' specified standards and whether external variables interfered with the correct home storage., Methods: This was a prospective observational study. Patients with a confirmed diagnosis of rheumatoid arthritis, ankylosing spondylitis or psoriatic arthritis who were using a biologic exclusively dispensed by Unified Public System were included. Storage temperature was measured by digital thermometer inserted into the refrigerator of the participant's home. Fisher's exact test was performed to cross-reference the temperature data and the qualitative variables obtained using an epidemiologic questionnaire. Mean, minimum, maximum values and standard deviation were described in the quantitative data. Mann-Whitney non-parametric test was performed to the association between temperature excursion and the number of people in the house., Results: A total of 81 participants were included and 67 (82.71%) did not maintain home storage correctly. The maximum temperature observed among all patients was 15.5 °C, the minimum was - 4.4 °C and the average was 5.6 °C (standard deviation 2.8); 10 (12.3%) had at least one negative temperature measured. The average time for participants who had an inadequate temperature record was 8 h and 31 min. Nine participants (90%) who stored the medication into the shelf/drawer below the freezer had a temperature excursion (p = 0.011). Most of the participants (88.5%) who stored their biopharmaceutical near the back side, close to the wall of the refrigerator had a negative temperature record (p < 0.001)., Conclusion: Most of the study participants (82.71%) did not maintain adequate home storage conditions for their biopharmaceutical. Intrinsic factors of household refrigerators may be involved in temperature deviations.

Introduction: Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA)., Objective: Our objective was to compare the incidence rates (IRs) of adverse events in tofacitinib clinical trials and real-world observational data for alternative treatments., Methods: The tofacitinib "dose-comparison cohort" included months 0-12 of two phase III studies (tofacitinib 5 [n = 238] and 10 [n = 236] mg twice daily [BID]); the "all-tofacitinib comparison cohort" (n = 783) included two phase III and one ongoing long-term extension study (data cutoff May 2016). An "observational comparison cohort" (n = 5799) comprised patients initiating a conventional synthetic disease-modifying antirheumatic drug (DMARD), biologic DMARD, or apremilast in the US Truven MarketScan database from 2010 to 2015. IRs for serious infections (SIEs; requiring hospitalization), herpes zoster (HZ), malignancies (excluding non-melanoma skin cancer [NMSC]), NMSC, and major adverse cardiovascular events (MACE) across cohorts were qualitatively compared., Results: IRs (patients with events/100 patient-years) for SIEs were similar between the tofacitinib dose-comparison cohort (5 mg BID: 1.3; 10 mg BID: 2.0) and the observational comparison cohort (1.1-7.9; treatment dependent). The tofacitinib dose-comparison cohort had a higher rate of HZ (5 mg BID: 2.0; 10 mg BID: 2.7) than did the observational comparison cohort (0.8-2.0). IRs for NMSC were generally lower in the all-tofacitinib comparison cohort (0.5) than in the observational comparison cohort (0.4-6.0). IRs for MACE, malignancies excluding NMSC, and NMSC were similar between cohorts., Conclusion: In patients with PsA, tofacitinib had a safety profile similar to that of other systemic therapies in real-world settings, except for the risk of HZ, a known risk of tofacitinib., Trial Registration: ClinicalTrials.gov: NCT01877668; NCT01882439; NCT01976364.

Spondyloarthritis is a group of chronic inflammatory systemic diseases characterized by axial and/or peripheral joints inflammation, as well as extra-articular manifestations. The classification axial spondyloarthritis is adopted when the spine and/or the sacroiliac joints are predominantly involved. This version of recommendations replaces the previous guidelines published in May 2013.A systematic literature review was performed, and two hundred thirty-seven studies were selected and used to formulate 29 recommendations answering 15 clinical questions, which were divided into four sections: diagnosis, non-pharmacological therapy, conventional drug therapy and biological therapy. For each recommendation the level of evidence supporting (highest available), the strength grade according to Oxford, and the degree of expert agreement (inter-rater reliability) is informed.These guidelines bring evidence-based information on clinical management of axial SpA patients, including, diagnosis, treatment, and prognosis.

Background: The Indian Takayasu Clinical Activity Score (ITAS2010) was developed in 2010 as an assessment tool for disease activity in patients with Takayasu arteritis (TA). It has since been widely used in different studies and in clinical practice for the management of patients with TA. The present study aims to translate the ITAS2010 into Brazilian Portuguese language and to validate it for use in clinical practice in Brazil., Methods: For this cross-sectional study, the ITAS2010 was translated in accordance with the guidelines described by Beaton et al. and then applied with 27 patients with TA on three assessments by two rheumatologists working independently. To measure interrater agreement, the assessments were performed on the same day within approximately 1 hour. One of the rheumatologists performed a second evaluation of patients with TA within 7 to 14 days to measure intrarater agreement., Results: The correlation coefficient for the ITAS2010 score between the two raters was high (r = 0.916; p < 0.0001), as well as the intraclass correlation coefficient (ICC) [0.918 with a 95% confidence interval (95CI): 0.828-0.962]. The correlation coefficient and the ICC for intrarater agreement were moderate for ITAS2010 (r = 0.633; p < 0.0001 and ICC = 0.594; 95CI: 0.292-0.790). The ITAS2010 at baseline was compared with the physician's global assessment (PGA) and with Kerr's criteria for detecting disease activity in TA. Higher ITAS2010 scores were observed in patients with active and grumbling/persistent disease than in those presenting inactive disease according to the PGA [1.5 (0.0-3.0) vs. 0.0 (0.0-0.0); p = 0.0025]. Patients with active disease according to the Kerr's criteria had also higher ITAS2010 scores than those considered in remission [3.0 (3.0-7.0) vs. 0.0 (0.0-0.0); p = 0.0068]., Conclusions: The Brazilian Portuguese version of the ITAS2010 is a valid and reproducible tool for the assessment of disease activity in TA and it is an additional tool for the routine evaluation of Brazilian patients with TA.

Background: Benzbromarone is a uricosuric drug that has been used in the treatment of gout over the last 30 years. Due to its potent inhibition of the dominant apical (luminal) urate exchanger in the human proximal tubule URAT1, it reduces the urate reabsorption, diminishing serum urate levels and therefore preventing gout flares. Through several clinical trials, Benzbromarone has been proved effective and safe, inclusive in patients with chronic kidney disease and as combination therapy with allopurinol. Due to hepatotoxicity reports, it was withdrawn from the European market by the manufacturer, however many authors have questioned the product's withdrawal due to a lack of clinical evidence in order to support its hepatotoxicity. Benzbromarone is still available in several European countries, New Zealand, Brazil and several other countries. Despite the product's marketing over more than 20 years after the first hepatotoxicity reports, we have found only five reports in our literature search, and no prospective or retrospective study correlating hepatotoxicity with benzbromarone use., Short Conclusion: Benzbromarone is a safe and effective molecule for the treatment of gout. However, due to in vitro and in vivo data related to hepatotoxicity, it is prudent to prescribe it with some caution, especially for patients with an already known liver condition.

The two co-authors of the mentioned above article were incorrect. The correct are authors should have been "P. A. Beltrán" instead of "P. A. B. Roa" and "J. F. Diaz-Coto" instead of "L. Diaz Soto".