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Introduction: The safety and efficacy of upadacitinib 15 mg (UPA15) through week 216 was evaluated in patients with rheumatoid arthritis (RA) from the long-term extension (LTE) of the phase 3 SELECT-CHOICE study. Methods: Patients with RA refractory to biologic disease-modifying antirheumatic drugs (bDMARDs) were randomized to UPA15 or abatacept (ABA) for 24 weeks. During the open-label LTE, patients on ABA switched to UPA15 at week 24, and those on UPA15 continued treatment. The safety and efficacy of continuous UPA15, and ABA to UPA15, are summarized through week 216. Results: The LTE was comprised of 91.4% (n = 277/303) of patients that initially received UPA15, and 89.6% (n = 277/309) that initially received ABA. Of patients on UPA15 in the LTE (n = 547), 28.3% (n = 155/547) discontinued the study drug by week 216. Relative to other adverse events of special interest, and largely consistent with previous findings at week 24, higher rates of serious infection, COVID-19, herpes zoster, and elevated creatine phosphokinase were reported, while rates of malignancy excluding nonmelanoma skin cancer (NMSC), NMSC, major adverse cardiovascular event (MACE), and venous thromboembolism (VTE) were low. Long-term safety data with UPA through week 216 aligned with previous observations and no new safety risks were identified, including in patients who switched from ABA to UPA15. Proportions of patients achieving 28-joint disease activity score based on C-reactive protein (DAS28[CRP]) < 2.6/ ≤ 3.2, clinical disease activity index (CDAI) and simple disease activity index (SDAI) low disease activity/remission, ≥ 20%/50%/70% improvement in the American College of Rheumatology (ACR20/50/70) response criteria, and Boolean remission were maintained or improved with UPA15 through week 216. Improvements in the Health Assessment Questionnaire-Disability Index (HAQ-DI), patient's assessment of pain, and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were also maintained or improved with UPA15 through week 216. Across all efficacy endpoints, similar results were observed in patients who switched from ABA to UPA15 versus continuous UPA15. Patients with an inadequate response to ≥ 1 prior tumor necrosis factor (TNF) inhibitor (UPA15: n = 263/303, 86.8%; ABA to UPA15: n = 273/309, 88.3%) showed similar responses to the total population. Conclusions: The long-term safety profile of UPA was consistent with previous findings and the broader RA clinical program. Compared to the primary analyses at week 24, efficacy responses were maintained or further improved with UPA15 through week 216 in patients with RA. Trial registration, ClinicalTrials.gov identifier: NCT03086343. Plain Language Summary: A long-term study looked at a drug named upadacitinib to treat people with rheumatoid arthritis (RA), a disease that causes joint pain and damage. The study included patients whose RA was not improved by other injectable medicines. The study compared upadacitinib with another drug called abatacept. After 24 weeks, patients who were taking abatacept switched to upadacitinib, and patients taking upadacitinib continued on upadacitinib treatment for over 4 years. The researchers looked at how well the treatments worked over the long-term and if there were any side effects. The side effects with upadacitinib treatment in this long-term study were similar to side effects reported in previous studies with upadacitinib. The researchers also found that upadacitinib helped to lessen the symptoms of RA over time and helped patients complete their daily activities and reduced their pain and tiredness. This was true for patients who switched from abatacept to upadacitinib after 24 weeks and for patients who took upadacitinib from the start of the study. Patients who had not responded to other medicines also had similar improvements with upadacitinib. In conclusion, upadacitinib can help people with RA over the long term and no new safety risks were found. [ABSTRACT FROM AUTHOR]

Morphometry of striated muscle fibres is critical for monitoring muscle health and function. Here, we evaluated functional parameters of skeletal and cardiac striated muscle in two experimental models using the Morphometric Analysis of Muscle Fibre tool (MusMA). The collagen‐induced arthritis model was used to evaluate the function of skeletal striated muscle and the non‐alcoholic fatty liver disease model was used for cardiac striated muscle analysis. After euthanasia, we used haeamatoxylin and eosin stained sections of skeletal and cardiac muscle to perform muscle fibre segmentation and morphometric analysis. Morphometric analysis classified muscle fibres into six subpopulations: normal, regular hypertrophic, irregular hypertrophic, irregular, irregular atrophic and regular atrophic. The percentage of atrophic fibres was associated with lower walking speed (p = 0.009) and lower body weight (p = 0.026), respectively. Fibres categorized as normal were associated with maximum grip strength (p < 0.001) and higher march speed (p < 0.001). In the evaluation of cardiac striated muscle fibres, the percentage of normal cardiomyocytes negatively correlated with cardiovascular risk markers such as the presence of abdominal adipose tissue (p =.003), miR‐33a expression (p =.001) and the expression of miR‐126 (p =.042) Furthermore, the percentage of atrophic cardiomyocytes correlated significantly with the Castelli risk index II (p =.014). MusMA is a simple and objective tool that allows the screening of striated muscle fibre morphometry, which can complement the diagnosis of muscle diseases while providing functional and prognostic information in basic and clinical research. [ABSTRACT FROM AUTHOR]

Background: Clinical experience has shown that a single measure is not sufficient to assess disease activity in rheumatoid arthritis (RA). Various clinimetric tools are necessary to address the many clinical situations that can arise. Methods: In order to develop a comprehensive measurement tool, the Pan American League of Associations for Rheumatology searched for the most frequent measures of disease activity applied in RA by means of a semi-systematic review of the available literature. Results: We found that the most frequently reported measures of disease activity were the 28-joint Disease Activity Score, C-reactive protein, and the erythrocyte sedimentation rate, followed by patient-reported measures of pain and stiffness and many other composite indices and patient-reported outcome measures. The most frequent physician-reported sign of disease was the swollen joint count, and the most frequently self-reported feature was the increase in disease activity or flares. Conclusion: In this article, we present a new clinimetric tool developed based on expert consensus and on data retrieved from our search. Disease activity can be better assessed by combining various data sources, such as clinical, laboratory, and self-reported outcomes. These variables were included in our novel clinimetric tool. Key Points • The goal of treatment of RA is to achieve the best possible control of inflammation, or even remission; therefore, disease management should include systematic and regular evaluation of inflammation and health status. • Clinimetric tools evaluate a series of variables (e.g., symptoms, functional capacity, disease severity, quality of life, disease progression) and can reveal substantial prognostic and therapeutic differences between patients. • Our clinimetric tool, which is based on a combination of data (e.g., clinical variables, laboratory results, PROMs), can play a relevant role in patient assessment and care. [ABSTRACT FROM AUTHOR]

This study investigated the impacts of CCR5 promoter region polymorphisms on the development of systemic lupus erythematosus (SLE) by comparing CCR5 genotypes and haplotypes from SLE patients with ethnically matched controls. A total of 382 SLE patients (289 European‐derived and 93 African‐derived) and 375 controls (243 European‐derived and 132 African‐derived) were genotyped for the CCR2‐64I G > A (rs1799864), CCR5‐59353 C > T (rs1799988), CCR5‐59356 C > T (rs41469351), CCR5‐59402 A > G (rs1800023) and CCR5‐59653 C > T (rs1800024) polymorphisms through polymerase chain reaction‐restriction fragment length polymorphism and direct sequencing. Previous data from CCR5Δ32 analysis was included in the study to infer the CCR5 haplotypes and as a possible confounding factor in the binary logistic regression. European‐derived patients showed a higher frequency of CCR5 wild‐type genotype (conversely, a reduced frequency of Δ32 allele) and a reduced frequency of the HHG*2 haplotype compared to controls; both factors significantly affecting disease risk [p =.003 (OR 3.5, 95%CI 1.6–7.5) and 2.0% vs. 7.2% (residual p = 2.9E − 5), respectively]. Additionally, the HHA/HHB, HHC and HHG*2 haplotype frequencies differed between African‐derived patients and controls [10% vs. 20.5% (residual p =.003), 29.4% vs. 17.4% (residual p =.003) and 3.9% vs. 0.8% (residual p =.023), respectively]. Considering the clinical manifestations of the disease, the CCR5Δ32 presence was confirmed as a susceptibility factor to class IV nephritis in the African‐derived group and when all patients were grouped for comparison [pcorrected =.012 (OR 3.0; 95%CI 3.0–333.3) and pcorrected =.0006 (OR 6.8; 95%CI 1.9–24.8), respectively]. In conclusion, this study indicates that CCR5 promoter polymorphisms are important disease modifiers in SLE. Present data reinforces the CCR5Δ32 polymorphism as a protective factor for the development of the disease in European‐derived patients and as a susceptibility factor for class IV nephritis in African‐derived patients. Furthermore, we also described a reduced frequency of HHA/HHB and an increased frequency of HHC and HHG*2 haplotypes in African‐derived patients, which could modify the CCR5 protein expression in specific cell subsets. [ABSTRACT FROM AUTHOR]

Janus kinases (JAKs) are a family of cytosolic tyrosine kinases that regulate cytokine signal transduction, including cytokines involved in a range of inflammatory diseases, such as RA, psoriasis, atopic dermatitis and IBD. Several small-molecule JAK inhibitors (JAKis) are now approved for the treatment of various immune-mediated inflammatory diseases. There are, however, key differences between these agents that could potentially translate into unique clinical profiles. Each JAKi has a unique chemical structure, resulting in a distinctive mode of binding within the catalytic cleft of the target JAK, and giving rise to distinct pharmacological characteristics. In addition, the available agents have differing selectivity for JAK isoforms, as well as off-target effects against non-JAKs. Other differences include effects on haematological parameters, DNA damage repair, reproductive toxicity and metabolism/elimination. Here we review the pharmacological profiles of the JAKis abrocitinib, baricitinib, filgotinib, peficitinib, tofacitinib and upadacitinib. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the function of a cohort of patients with rheumatoid arthritis (RA) from the core set of the International Classification of Functioning and Health (ICF) for RA over 12 months. Methods: We used prospective longitudinal data to conduct a cohort study among a well-characterized group of RA patients. Ninety RA patients aged between 40 and 70 years were included in the study. Patients were evaluated at baseline and after 12 months. Age, disease duration, current smoking, erosions, disease activity, functional test, disability and physical activity were evaluated. Then, the ICF core set classification for RA was applied. Results: 81 patients completed the assessments, the majority of patients were female (88.9%) and the mean age was 56.5 ± 7.3 years. At baseline, the median disease activity was 3.0. There was a statistically significant (p < 0.02) improvement in "Exercise tolerance functions" over 12 months and also a statistically significant (p < 0.001) decrease in "Muscle strength functions" over 12 months. The activity and participation domain showed a weak correlation with the clinical data of the DAS28-PCR (p<0.02). Conclusion: We conclude that relevant aspects of the ICF Core Set for RA were able to adequately express the physical and functional factors of the RA cohort. This tool provides a common language for the interdisciplinary team, which can enhance the use of timely interventions to prevent physical disability in clinical practice. [ABSTRACT FROM AUTHOR]

Aim: Certolizumab pegol (CZP), an Fc‐free, PEGylated tumor necrosis factor inhibitor (TNFi), has shown rapid and sustained reduction in signs and symptoms of rheumatoid arthritis (RA). Elevated rheumatoid factor (RF) level has been associated with RA disease progression and poorer TNFi response. We assessed the efficacy of CZP in patients with early and established RA across baseline RF levels. Methods: This post‐hoc analysis included data from 6 trials: C‐OPERA (NCT01451203), pooled RAPID trials (RAPID‐1 [NCT00152386], RAPID‐2 [NCT00160602], J‐RAPID [NCT00791999], RAPID‐C [NCT02151851]), and EXXELERATE (NCT01500278). Patients who received CZP or placebo/comparator with methotrexate (MTX) were categorized by baseline RF quartiles. Efficacy was assessed with Disease Activity Score‐28 erythrocyte sedimentation rate (DAS28‐ESR). Results: Overall, 316, 1537, and 908 patients were included in C‐OPERA, pooled RAPID trials, and EXXELERATE, respectively. Patient demographics and baseline disease characteristics were similar between treatment groups and across RF quartiles. DAS28‐ESR low disease activity (LDA) and remission (REM) rates were numerically higher in the CZP + MTX group than PBO + MTX group at weeks 12 and 24, across RF quartiles. LDA and REM rates in the CZP + MTX groups were comparable across RF quartiles at weeks 12 and 24. Mean DAS28‐ESR decreased from week 0 to week 24 in the CZP + MTX groups, across RF quartiles. Conclusion: CZP showed steady efficacy across baseline RF quartiles in patients with early and established RA, over 24 weeks. CZP treatment may be considered in patients with RA irrespective of baseline RF levels and time from diagnosis. [ABSTRACT FROM AUTHOR]

To perform a systematic review with meta-analysis to verify muscle strength, muscle mass, and physical function of patients with systemic lupus erythematosus (SLE) and compare then with healthy individuals and patients with rheumatoid arthritis (RA). A systematic review with meta-analysis of observational studies published in English up to 2022 was performed using MEDLINE (via PubMed) and other relevant sources. Search strategies were based on pre-defined keywords and medical subject headings. The methodological quality of the studies was assessed using the Newcastle–Ottawa Scale. Mean difference (MD) or standardized mean difference (SMD) and 95% confidence intervals (CI) were combined using a random-effects model. Sensitivity analyses were performed when necessary. The significance level was set at p < 0.05. The systematic review included 19 studies and the meta-analysis included 11 studies. SLE patients appear to have less muscle strength assessed by handgrip than healthy controls (SLE = 21.74 kg; healthy controls = 29.34 kg; p < 0.05). SLE patients seem to have greater strength than patients with RA, but this difference was not statistically significant (RA = 17.24 kg; p = 0.210). However, in the sensitivity analysis, SLE group without deforming arthropathy showed higher muscle strength than the RA (p = 0.0001). SLE patients with deforming arthropathy have lower muscle strength compared to SLE patients without deforming arthropathy (p < 0.01). Muscle mass was similar in SLE patients compared to the RA group and healthy controls (p > 0.05). However, RA patients have a higher BMI than the two groups (p < 0.05). Patients with SLE have regular physical function. Muscle strength is affected in SLE patients. SLE patients with deforming arthropathy have less muscle strength than patients without deforming arthropathies. [ABSTRACT FROM AUTHOR]

Introduction: Self-reported disability is potentially influenced by many factors in patients with rheumatoid arthritis (RA). In this sense, we evaluated the association between self-reported disability and (1) clinical features, (2) muscle strength and (3) physical performance over time among patients with RA from two distinct patient cohorts. Materials and methods: Two independent prospective RA cohorts were analyzed. The Health Assessment Questionnaire (HAQ), Disease Activity Score in 28 Joints (DAS28), handgrip test, chair stand test, timed-up-and-go (TUG) test and Short Physical Performance Battery (SPPB) were performed at baseline and in follow-up. T test for independent samples, Mann-Whitney U test, Spearman correlation coefficients and linear regression with generalized estimating equations were performed to assess associations between individual constructs at baseline and over time. Results: A total of 205 total RA patients were included [North American Cohort (n = 115); Brazilian Cohort (n = 90)]. At enrollment, Brazilian men had better HAQ than North American men (p<0.001). Brazilian patients overall had lower muscle strength than North American patients (p<0.05). HAQ was associated with DAS28, handgrip test, chair stand test, TUG and SPPB (p<0.001) in both cohorts. Worsening of the DAS28 and chair stand test were each associated with worsening in HAQ in longitudinal analysis over time. Worsening of handgrip was also associated in with worsening HAQ in both cohorts (p<0.05). A worse TUG test was associated with worsening in HAQ in Brazilian cohort (p<0.05) and a worse SPPB was associated with worsening in HAQ in North American cohort (p<0.05). Conclusion: Greater disability measured by HAQ is closely associated with disease activity, pain, muscle strength, and physical performance among RA. Worsening in self-reported disability correlate with worsening clinical factors including objectively-observed physical function. [ABSTRACT FROM AUTHOR]

Metabolomic analysis provides a wealth of information that can be predictive of distinctive phenotypes of pathogenic processes and has been applied to better understand disease development. Rheumatoid arthritis (RA) is an autoimmune disease with the establishment of chronic synovial inflammation that affects joints and peripheral tissues such as skeletal muscle and bone. There is a lack of useful disease biomarkers to track disease activity, drug response and follow-up in RA. In this review, we describe potential metabolic biomarkers that might be helpful in the study of RA pathogenesis, drug response and risk of comorbidities. TMAO (choline and trimethylamine oxide) and TCA (tricarboxylic acid) cycle products have been suggested to modulate metabolic profiles during the early stages of RA and are present systemically, which is a relevant characteristic for biomarkers. Moreover, the analysis of lipids such as cholesterol, FFAs and PUFAs may provide important information before disease onset to predict disease activity and treatment response. Regarding therapeutics, TNF inhibitors may increase the levels of tryptophan, valine, lysine, creatinine and alanine, whereas JAK/STAT inhibitors may modulate exclusively fatty acids. These observations indicate that different disease modifying antirheumatic drugs have specific metabolic profiles and can reveal differences between responders and non-responders. In terms of comorbidities, physical impairment represented by higher fatigue scores and muscle wasting has been associated with an increase in urea cycle, FFAs, tocopherols and BCAAs. In conclusion, synovial fluid, blood and urine samples from RA patients seem to provide critical information about the metabolic profile related to drug response, disease activity and comorbidities. [ABSTRACT FROM AUTHOR]

Introduction: Systemic lupus erythematosus (SLE) is a multifactorial disease and MBL2 genetic variants, which are associated to differential peripheral MBL levels, potentially affect its etiology and increase infection risk in this population. Objective: To evaluate the potential association of MBL2 polymorphisms of the coding and promoter gene region and haplotypes on hospitalization, number of admission and days of admission for major infection causes in Brazilian SLE patients. Methods: 325 SLE patients from a southern Brazilian outpatient SLE clinic were genotyped in 2006 for MBL2 gene polymorphisms from coding and promoter region (rs1800450, rs1800451, rs5030737, rs11003125, and rs7096206) and followed until 2016. Clinical and laboratory data from each patient were obtained and information regarding the need for hospitalization, the number of admissions and number of days admitted for infection treatment were compiled and compared with MBL2 gene polymorphisms and haplotypes. A linear regression analysis was constructed considering the variables of bivariate which demonstrated an association (p<0.05) and variables which had a theoretical basement. Results: No difference was found in polymorphism prevalence when comparing the group that was admitted for infection treatment and the group who did not. Allele C, and haplotypes LY and HY correlated with more infection hospitalizations [wild-type homozygosis for C: 2 (IQR 1–3), heterozygosis for C: 3 (IQR 2–6) p=0.038; LY 2 (IQR 1–3) p=0.049; HY 2 (IQR 1–3) p=0.005] and haplotype HY carriers stayed fewer days in hospital for infection treatment: 18 (IQR 10–38) p=0.041. When linear regression was applied HY associated with shorter admission time for infections (−18.11 days, p=0.021) and HY (−1.52 admission, p 0.001) carriers with older age at diagnosis had less admissions for infection (HY regression model: −0.42, p=0.006; LY regression model −0.04, p=0.010; −0.04, p=0.013). Conclusion: The presence of the HY promoter haplotype associated to fewer in hospital care for infection treatment probably due to higher MBL plasma levels. Also, HY haplotype and older age at SLE diagnosis is related to less admissions for infection. This factor should be taken into consideration, since infection is a very import cause of mortality in SLE patients being also related to aggressive immunosuppressive treatment. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis(RA) and osteoarthritis(OA) patients showed systemic manifestations that may lead to a reduction in muscle strength, muscle mass and, consequently, to a reduction in functionality. On the other hand, moderate intensity resistance training(MIRT) and high intensity resistance training(HIRT) are able to improve muscle strength and muscle mass in RA and OA without affecting the disease course. However, due to the articular manifestations caused by these diseases, these patients may present intolerance to MIRT or HIRT. Thus, the low intensity resistance training combined with blood flow restriction(LIRTBFR) may be a new training strategy for these populations. Objective: To perform a systematic review with meta-analysis to verify the effects of LIRTBFR on muscle strength, muscle mass and functionality in RA and OA patients. Materials and methods: A systematic review with meta-analysis of randomized clinical trials(RCTs), published in English, between 1957–2021, was conducted using MEDLINE(PubMed), Embase and Cochrane Library. The methodological quality was assessed using Physiotherapy Evidence Database scale. The risk of bias was assessed using RoB2.0. Mean difference(MD) or standardized mean difference(SMD) and 95% confidence intervals(CI) were pooled using a random-effects model. A P<0.05 was considered statistically significant. Results: Five RCTs were included. We found no significant differences in the effects between LIRTBFR, MIRT and HIRT on muscle strength, which was assessed by tests of quadriceps strength(SMD = -0.01[-0.57, 0.54], P = 0.96; I² = 58%) and functionality measured by tests with patterns similar to walking(SMD = -0.04[-0.39, 0.31], P = 0.82; I² = 0%). Compared to HIRT, muscle mass gain after LIRTBFR was reported to be similar. When comparing LIRTBFR with low intensity resistance training without blood flow restriction(LIRT), the effect LIRTBFR was reported to be higher on muscle strength, which was evaluated by the knee extension test. Conclusion: LIRTBFR appears to be a promising strategy for gains in muscle strength, muscle mass and functionality in a predominant sample of RA and OA women. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are influenced by genetic variants in immune system HLA genes. The Class II Major Histocompatibility Complex Transactivator (CIITA) is an important co‐activator of the HLA transcriptional complex; the single nucleotide variant (SNV) rs3087456 localized in the gene promoter region (−168 A/G) has been reported as able to modify its transcription level. In our study, we assessed CIITA rs3087456 SNV in 1,044 Brazilians from two Brazilian regions (Northeast and South) to verify the association with susceptibility and clinical manifestations of (SLE) and (RA) using TaqMan SNP Genotyping Assays System. We observed a protection for a recessive model (GG x AA+AG) for RA susceptibility and increased risk for erosion development in AG genotype patients. No significant association was observed for SLE susceptibility; however, we observed significant increased risk for Class IV and V nephritis development in G allele and GG genotype patients. In conclusion, we showed the contribution of CIITA rs3087456 to SLE or RA clinical features and RA susceptibility in the studied populations. [ABSTRACT FROM AUTHOR]

Objectives To assess efficacy, pharmacokinetics (PK) and safety of intravenous (i.v.) golimumab in patients with polyarticular-course JIA (pc-JIA). Methods Children aged 2 to <18 years with active pc-JIA despite MTX therapy for ≥2 months received 80 mg/m2 golimumab at weeks 0, 4, then every 8 weeks through week 52 plus MTX weekly through week 28. The primary and major secondary endpoints were PK exposure and model-predicted steady-state area under the curve (AUCss) over an 8-week dosing interval at weeks 28 and 52, respectively. JIA ACR response and safety were also assessed. Results In total, 127 children were treated with i.v. golimumab. JIA ACR 30, 50, 70, and 90 response rates were 84%, 80%, 70% and 47%, respectively, at week 28 and were maintained through week 52. Golimumab serum concentrations and AUCss were 0.40 µg/ml and 399 µg ⋅ day/ml at week 28. PK exposure was maintained at week 52. Steady-state trough golimumab concentrations and AUCss were consistent across age categories and comparable to i.v. golimumab dosed 2 mg/kg in adults with rheumatoid arthritis. Golimumab antibodies and neutralizing antibodies were detected via a highly sensitive drug-tolerant assay in 31% (39/125) and 19% (24/125) of patients, respectively. Median trough golimumab concentration was lower in antibody-positive vs antibody-negative patients. Serious infections were reported in 6% of patients, including one death due to septic shock. Conclusion Body surface area-based dosing of i.v. golimumab was well tolerated and provided adequate PK exposure for clinical efficacy in paediatric patients with active pc-JIA. ClinicalTrials.gov number NCT02277444 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Turbulent flows are often bounded by regions of irrotational or non-turbulent flow, where the magnitude of the potential velocity fluctuations can be surprisingly high. This includes virtually all turbulent free-shear flows and also turbulent boundary layers, and is particularly true near the so-called turbulent/non-turbulent interface (TNTI) layer, which separates the regions of turbulent and non-turbulent fluid motion. In the present work, we show that in the non-turbulent region and for distances $x_2$ sufficiently far from the TNTI layer, the asymptotic variation laws for the variance of the velocity fluctuations $\langle u_i^{2} \rangle$ ($i=1,2,3$), Taylor micro-scale $\lambda$ and viscous dissipation rate $\varepsilon$ depend on the shape of the kinetic energy spectrum in the infrared region $E(k) \sim k^{n}$. Specifically, by using rapid distortion theory (RDT), we show that for Saffman turbulence ($E(k) \sim k^{2}$), we obtain the asymptotic laws $\langle u_i^{2} \rangle \sim x_2^{-3}$ ($i=1,2,3$), $\lambda \sim x_2$ and $\varepsilon \sim x_2^{-5}$. Additionally, we confirm the classical results obtained by Phillips (Proc. Camb. Phil. Soc., vol. 51, 1955, p. 220) for Batchelor turbulence ($E(k) \sim k^{4}$), with $\langle u_i^{2} \rangle \sim x_2^{-4}$ ($i=1,2,3$), $\lambda \sim x_2$ and $\varepsilon \sim x_2^{-6}$. The new theoretical results are confirmed by direct numerical simulations (DNS) of shear-free turbulence and are shown to be independent of the Reynolds number. Therefore, these results are expected to be valid in other flow configurations, such as in turbulent planar jets or wakes, provided the kinetic energy spectra in the turbulence region can be described by a Batchelor or a Saffman spectrum. [ABSTRACT FROM AUTHOR]

Objective: To assess upadacitinib monotherapy versus methotrexate (MTX) in MTX-naïve Japanese patients with rheumatoid arthritis (RA) from the Phase 3 SELECT-EARLY study. Methods: Japanese patients were randomized 2:1:1:1 to upadacitinib 7.5, 15, or 30mg daily or MTX 7.5mg/week (titrated to ≤ 15mg/week). Efficacy endpoints included the proportion of patients reporting 20% improvement in American College of Rheumatology criteria (ACR20) at week 12 and change from baseline in modified Total Sharp Score (mTSS) at week 24. Other efficacy outcomes were also assessed at weeks 12 and/or 24. Safety was assessed over 24 weeks. Results: Of 138 Japanese patients enrolled, significantly more patients treated with upadacitinib 7.5 and 15mg, but not 30mg, reported ACR20 responses versus MTX at week 12. Significantly smaller changes from baseline in mTSS were observed with upadacitinib 15 and 30mg, but not 7.5 mg, versus MTX at week 24. Upadacitinib demonstrated an acceptable safety profile; herpes zoster occurred in 3.6%, 7.4%, and 7.1% of patients treated with upadacitinib 7.5, 15, and 30mg, respectively. Conclusion: Similar to the global study population, upadacitinib demonstrated clinical efficacy superior to placebo in the Japanese subpopulation. Among upadacitinib-treated patients, herpes zoster was least common with 7.5 mg. [ABSTRACT FROM AUTHOR]

Objective: To report the 2‐year efficacy and safety of tocilizumab (TCZ) in patients with polyarticular‐course juvenile idiopathic arthritis (JIA). Methods: Patients ages 2–17 years with active polyarticular‐course JIA, in whom treatment with methotrexate was unsuccessful, received 16 weeks of open‐label intravenous TCZ in part 1 (once every 4 weeks: 8 mg/kg or 10 mg/kg for body weight [BW] <30 kg; 8 mg/kg for BW ≥30 kg). Assessments were based on the JIA–American College of Rheumatology (ACR) response (defined as percentage of improvement in ≥3 of the 6 JIA core response variables [CRVs]). Patients with at least a JIA‐ACR30 response (defined as ≥30% improvement in ≥3 of the 6 JIA CRVs without worsening in >1 of the remaining JIA CRVs by >30%) at week 16 were randomly assigned (1:1) to receive TCZ or placebo in part 2. Patients remained in part 2 until either week 40 or the occurrence of JIA flare. Upon starting part 3, all patients received open‐label TCZ. At week 104 of the study, efficacy was assessed using JIA‐ACR50/70/90 response rates (defined as 50%, 70%, or 90% improvement, respectively), achievement of inactive disease, and the Juvenile Arthritis Disease Activity Score in 71 joints (JADAS‐71). Safety was assessed in the all‐exposure population per 100 patient‐years of exposure. Results: Overall, 188 patients entered part 1, 166 patients entered part 2, and 160 patients entered part 3. By week 104, among the 188 patients in the modified intent‐to‐treat group who received TCZ, JIA‐ACR50/70/90 response rates were 80.3%/77.1%/59.6%, respectively, the median JADAS‐71 score decreased from 3.6 at week 40 to 0.7 at week 104, 51.1% of patients had achieved inactive disease, and 31 of 66 patients who had been receiving glucocorticoids discontinued them. Adverse event (AE) and serious AE rates were 406.5 per 100 patient‐years and 11.1 per 100 patient‐years, respectively. The infection rate was 151.4 per 100 patient‐years, and the serious infection rate was 5.2 per 100 patient‐years. Conclusion: Patients treated with TCZ for polyarticular‐course JIA showed high‐level disease control for up to 2 years. The TCZ safety profile was consistent with that previously reported. [ABSTRACT FROM AUTHOR]

Introduction: In view of the method of diagnosing sarcopenia being complex and considered to be difficult to introduce into routine practice, the European Working Group on Sarcopenia in Older People (EWGSOP) recommends the use of the SARC-F questionnaire as a way to introduce assessment and treatment of sarcopenia into clinical practice. Only recently, some studies have turned their attention to the presence of sarcopenia in systemic sclerosis (SSc).There is no data about performance of SARC-F and other screening tests for sarcopenia in this population. Objective: To compare the accuracy of SARC-F, SARC-CalF, SARC-F+EBM, and Ishii test as screening tools for sarcopenia in patients with SSc. Methods: Cross-sectional study of 94 patients with SSc assessed by clinical and physical evaluation. Sarcopenia was defined according to the revised 2019 EWGSOP diagnostic criteria (EWGSOP2) with assessments of dual-energy X-ray absorptiometry, handgrip strength, and short physical performance battery (SPPB). As case finding tools, SARC-F, SARC-CalF, SARC-F+EBM and Ishii test were applied, including data on calf circumference, body mass index, limitations in strength, walking ability, rising from a chair, stair climbing, and self reported number of falls in the last year. The screening tests were evaluated through receiver operating characteristic (ROC) curves. Standard measures of diagnostic accuracy were computed using the EWGSOP2 criteria as the gold standard for diagnosis of sarcopenia. Results: Sarcopenia was identified in 15 (15.9%) patients with SSc by the EWGSOP2 criteria. Area under the ROC curve of SARC-F screening for sarcopenia was 0.588 (95% confidence interval (CI) 0.420–0.756, p = 0.283). The results of sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR) and diagnostic Odds Ratio (DOR) with the EWGSOP2 criteria as the gold standard were 40.0% (95% CI, 19.8–64.2), 81.0% (95% CI, 71.0–88.1), 2.11 (95% CI, 0.98–4.55), 0.74 (95% CI, 0.48–1.13) and 2.84 (95% CI, 0.88–9.22), respectively. SARC-CalF and SARC-F+EBM showed better sensitivity (53.3%, 95% CI 30.1–75.2 and 60.0%, 95% CI 35.7–80.2, respectively) and specificity (84.8%, 95% CI 75.3–91.1 and 86.1%, 95% CI 76.8–92.0, respectively) compared with SARC-F. The best sensitivity was obtained with the Ishii test (86.7%, 95% CI 62.1–96.3), at the expense of a small loss of specificity (73.4%, 95% CI 62.7–81.9). Comparing the ROC curves, SARC-F performed worse than SARC-CalF, SARC-F+EBM and Ishii test as a sarcopenia screening tool in this population (AUCs 0.588 vs. 0.718, 0.832, and 0.862, respectively). Direct comparisons between tests revealed differences only between SARC-F and Ishii test for sensitivity (p = 0.013) and AUC (p = 0.031). Conclusion: SARC-CalF, SARC-F+EBM, and Ishii test performed better than SARC-F alone as screening tools for sarcopenia in patients with SSc. Considering diagnostic accuracy and feasibility aspects, SARC-F+EBM seems to be the most suitable screening tool to be adopted in routine care of patients with SSc. [ABSTRACT FROM AUTHOR]

Copyright of Brazilian Journal of Kineanthropometry & Human Performance is the property of Brazilian Journal of Kineanthropometry & Human Performance and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Rheumatoid arthritis (RA) is an inflammatory disease that leads to altered body composition. The loss of lean mass with a preservation or increase in fat mass has been termed rheumatoid cachexia (RC), to contrast with classic cachexia, which is characterized by severe weight loss. There are limited data on the prevalence and progression of cachexia in RA over time, as well as on associated factors. Our aim was to determine the prevalence of cachexia and to determine associations with potential factors. Methods: This prospective cohort study recruited consecutively patients diagnosed with RA and followed for 1 year. The assessments were performed: clinical features, body composition, and physical function. RC and classic cachexia were assessed by several established diagnostic criteria. The pairwise Student's t test, Chi-square test, and GEE were performed (accepted at p ≤ 0.05). Results: Of 90 patients recruited, 81 completed the study. Most patients were women (88.9%), and the mean age was 56.5 ± 7.3 years. At baseline, the median DAS28-CRP was 3.0 (IQR, 1.0–3.0), 13.3–30.0% of the included patients had RC, while none met criteria for classic cachexia. The prevalence of cachexia did not change after 12 months. Disease activity status and treatment with biologic disease-modifying antirheumatic drugs were significantly associated with changes on body composition and physical function (p < 0.05). Conclusions: In this cohort, RC was common, while classic cachexia was absent. Disease activity and use of biologic therapies were associated with changes on body composition and physical function, underscoring the importance of aiming for remission when treating RA. Key Points • Rheumatoid cachexia is common in RA patients. • Classical cachexia is not often in RA patients. • Disease activity and use of biologic therapies are associated with changes on body composition and physical function. [ABSTRACT FROM AUTHOR]

Objective: The SELECT‐EARLY trial was undertaken to study the effect of upadacitinib, an oral, reversible Janus kinase 1–selective inhibitor, as monotherapy in patients with predominantly early rheumatoid arthritis who were naive for or had limited exposure to methotrexate (MTX). Methods: Patients (n = 947) were randomized 1:1:1 to receive once‐daily doses of upadacitinib 15 mg or 30 mg or weekly MTX (7.5–20 mg/week) for 24 weeks. The primary end points were the proportion of patients who met the American College of Rheumatology 50% (ACR50) improvement criteria at week 12, and the proportion in whom a Disease Activity Score in 28 joints using the C‐reactive protein level (DAS28‐CRP) of <2.6 was achieved at week 24. Data are presented through week 24. Results: At baseline, the median disease duration was 0.5 years (range 0–44 years). A total of 840 patients (89%) completed 24 weeks of treatment. The study met both primary end points for upadacitinib 15 mg and 30 mg versus MTX (ACR50 was achieved at week 12 in 52% and 56% of patients, respectively, versus 28% [P < 0.001], and DAS28‐CRP <2.6 was achieved at week 24 in 48% and 50% of patients, respectively, versus 19% [P < 0.001]). Statistically significant and clinically meaningful improvements in multiple patient‐reported outcomes (PROs) were recorded for both upadacitinib doses versus MTX. Overall, 88% of patients receiving upadacitinib 15 mg and 89% of patients receiving 30 mg, respectively, had no radiographic progression (modified total Sharp score ≤0) compared to 78% of those receiving MTX (P < 0.01). Through week 24, the frequency of treatment‐emergent adverse events was similar between the MTX arm (65%) and upadacitinib 15 mg arm (64%), but was slightly higher in the upadacitinib 30 mg arm (71%). Six deaths were reported (2 in the upadacitinib 15 mg arm, 3 in the upadacitinib 30 mg arm, and 1 in the MTX arm). Conclusion: Our findings indicate that patients receiving either dose of upadacitinib monotherapy experienced significant improvements in clinical, radiographic, and PROs compared to patients receiving MTX. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to compare the clinical features, damage accrual, and survival of patients with familial and sporadic systemic lupus erythematosus (SLE). Methods: A multi-ethnic, multinational Latin American SLE cohort was studied. Familial lupus was defined as patients with a first-degree SLE relative; these relatives were interviewed in person or by telephone. Clinical variables, disease activity, damage, and mortality were compared. Odds ratios (OR) and 95% confidence intervals (CI) were estimated. Hazard ratios (HR) were calculated using Cox proportional hazard adjusted for potential confounders for time to damage and mortality. Results: A total of 66 (5.6%) patients had familial lupus, and 1110 (94.4%) had sporadic lupus. Both groups were predominantly female, of comparable age, and of similar ethnic distribution. Discoid lupus (OR = 1.97; 95% CI 1.08–3.60) and neurologic disorder (OR = 1.65; 95% CI 1.00–2.73) were significantly associated with familial SLE; pericarditis was negatively associated (OR = 0.35; 95% CI 0.14–0.87). The SLE Disease Activity Index and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) were similar in both groups, although the neuropsychiatric (45.4% vs. 33.5%; p = 0.04) and musculoskeletal (6.1% vs. 1.9%; p = 0.02) domains of the SDI were more frequent in familial lupus. They were not retained in the Cox models (by domains). Familial lupus was not significantly associated with damage accrual (HR = 0.69; 95% CI 0.30–1.55) or mortality (HR = 1.23; 95% CI 0.26–4.81). Conclusion: Familial SLE is not characterized by a more severe form of disease than sporadic lupus. We also observed that familial SLE has a higher frequency of discoid lupus and neurologic manifestations and a lower frequency of pericarditis. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the impact of SEMA4A genetic variants on expression of sema4A protein and its relation to autoimmunity development in Systemic Lupus Erythematosus and Rheumatoid Arthritis patients. A total of 541 SLE patients, 390 RA patients and 607 healthy individuals were genotyped. We also assessed SEMA4A mRNA expression from whole blood cells and the in vitro protein production from resting and activated T lymphocytes as well as mature dendritic cells from healthy individuals stratified according to their genotypes for SLE/RA associated SEMA4A variants. Our results showed that T/T genotype for rs3738581 SNP is associated with both RA and SLE development (p =.000053, OR = 2.35; p =.0019, OR = 2.07, respectively; statistical power = 100%) and also to an increased in vitro sema4A production in active T lymphocytes. Our findings are indicative of a T cell-specific upregulation of sema4A in the presence of T/T genotype, being a risk factor for SLE and RA. [ABSTRACT FROM AUTHOR]

Introduction: Registries of spondyloarthritis (SpA) patients' follow-up provided evidence that tumor necrosis factor inhibitors (TNFi) increase the incidence of active tuberculosis infection (TB). However, most of these registries are from low burden TB areas. Few studies evaluated the safety of biologic agents in TB endemic areas. This study compares the TB incidence rate (TB IR) in anti-TNF-naïve and anti-TNFexperienced subjects with SpA in a high TB incidence setting. Methods: In this retrospective cohort study, medical records from patients attending a SpA clinic during 13 years (2004 to 2016) in a university hospital were reviewed. The TB IR was calculated and expressed as number of events per 105 patients/year; the incidence rate ratio (IRR) associated with the use of TNFi was calculated. Results: A total of 277 patients, 173 anti-TNF-naïve and 104 anti-TNF-experienced subjects, were evaluated; 35.7% (N = 35) of patients who were prescribed an anti- TNF drug were diagnosed with latent tuberculosis infection (LTBI). Total follow-up time (person-years) was 1667.8 for anti-TNF-naïve and 394.9 for anti-TNF-experienced patients. TB IR (95% CI) was 299.8 (37.4-562.2) for anti-TNF naïve and 1012.9 (25.3-2000.5) for anti-TNF experienced subjects. The IRR associated with the use of TNFi was 10.4 (2.3- 47.9). Conclusions: In this high TB incidence setting, SpA patients exposed to anti-TNF therapy had a higher incidence of TB compared to anti-TNF-naïve subjects, although the TB incidence in the control group was significant. [ABSTRACT FROM AUTHOR]

Copyright of Jornal de Pediatria is the property of Sociedade Brasileira de Pediatria and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: In rheumatoid arthritis (RA), little is known about clinical responses to treatment as predictors of patient-reported outcome (PRO) changes. In this post hoc analysis, we examined the relationship between clinical outcomes at week 12 and PRO changes at week 24 in patients with RA. Methods: In an open-label study, Latin American patients with moderate-to-severe RA and an inadequate response to methotrexate (MTX) were randomized to receive etanercept 50 mg/week plus MTX (ETN+MTX; n=281) or an additional conventional disease-modifying anti-rheumatic drug (DMARD) plus MTX (DMARD+MTX; n=142) for 24 weeks. The PROs included Health Assessment Questionnaire Disability Index (HAQ-DI), 36-item Short Form (SF-36), Physician and Patient Global Assessment scores (PGA, PtGA), Physician and Patient Satisfaction, and an activity impairment assessment. PRO changes at week 24 were calculated by week-12 improvements using the American College of Rheumatology criteria (ACR <20, ≥20 to <50, ≥50 to <70, and ≥70) and the 28-joint Disease Activity Scores (DAS28 ≥3.2, ≥2.6 to <3.2, and <2.6). Observed-cases data were analyzed using an ANCOVA model with linear contrast, adjusted for baseline PRO and ACR/DAS28 values. Results: For both ETN+MTX- and DMARD+MTX-treated patients, there was a significant linear trend between week-12 changes in ACR and DAS28 responses and week-24 changes in HAQ-DI (P<0.001 for all), with numerical improvements generally favoring ETN+MTX. Similar relationships were observed for SF-36, PGA, PtGA, Physician Satisfaction, Patient Satisfaction, and activity impairment. Conclusions: In patients with RA, clinical response after 12 weeks of treatment with ETN+MTX or DMARD+MTX could be a predictor of week-24 response for several PROs. Trial registration: ClinicalTrials.gov, NCT00848354. [ABSTRACT FROM AUTHOR]