The effect of antimalarials on the safety and persistence of treatment with biologic agents or Janus kinase inhibitors in rheumatoid arthritis.

OBJECTIVES: To test the association of use of antimalarials with the overall safety of treatment in RA patients receiving one or multiple courses of biologic (b)DMARDs or a Janus kinase inhibitor (JAKi). METHODS: BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their first bDMARD or JAKi. The present analysis includes RA patients recruited from January 2009 to October 2019, followed up over one or multiple (up to six) courses of treatment (latest date, 19 November 2019). The primary outcome was the incidence of serious adverse events (SAEs). Total and system-specific adverse events (AEs) and treatment interruption served as secondary outcomes. Negative binomial regression with generalized estimating equations (to estimate multivariate incidence rate ratios, mIRR) and frailty Cox proportional hazards models were used for statistical analyses. RESULTS: The number of patients enrolled was 1316 (2335 treatment courses, 6711 patient-years [PY]; 1254.5 PY on antimalarials). The overall incidence of SAEs was 9.2/100 PY. Antimalarials were associated with reduced risk of SAEs (mIRR: 0.49; 95% CI: 0.36, 0.68; P < 0.001), total AEs (0.68; 95% CI: 0.56, 0.81; P < 0.001), serious infections (0.53; 95% CI: 0.34, 0.84; P = 0.007) and total hepatic AEs (0.21; 95% CI: 0.05, 0.85; P = 0.028). Antimalarials were also related to better survival of treatment course (P = 0.003). There was no significant increase in the risk of cardiovascular AEs. CONCLUSION: Among RA patients on treatment with bDMARDs or JAKi, concomitant use of antimalarials was associated with reduced the incidence of serious and total AEs and with longer treatment course survival.

How Does Ultrasound Global OMERACT-EULAR Synovitis Score (GLOESS) for Rheumatoid Arthritis (RA) Activity Assessment Perform in Real-Life?

OBJECTIVE: This study aimed to assess the effectiveness of the Global OMERACT-EULAR Synovitis Score (GLOESS) of bilateral second to fifth metacarpophalangeal joints (MCP 2-5) in evaluating rheumatoid arthritis (RA) activity in a real-life setting. METHODS: This cross-sectional study included consecutive RA patients without hyperalgesia. Clinical data were extracted from electronic medical records. Evaluations were conducted on bilateral MCP 2-5 by two independent experts in musculoskeletal ultrasound (MSUS). Correlation between clinical and ultrasonographic parameters was analyzed, aiming to define a cutoff value for detecting disease activity. RESULTS: Sixty-nine patients were included. The mean DAS28-ESR was 4.3 (±1.4), and the median GLOESS was 7 (13). The correlation between GLOESS and DAS28 was moderate (r = .62; P < .05). A total GLOESS score of ≤3 and all joints with both GS and PD ≤1 showed good sensitivity and specificity for detecting disease activity (remission/low vs moderate/high, P = 0). CONCLUSION: In a real-life scenario, GLOESS for MCP 2-5 emerges as a valuable measure of RA activity. The optimal cutoff distinguishing remission/low from moderate/high disease activity was determined to be GLOESS ≤3, with all MCP joints exhibiting both GS and PD scores of ≤1.

Synovitis and Tenosynovitis on Ultrasound as Predictors of DMARD Tapering Failure in Patients with Long-Standing Rheumatoid Arthritis in Clinical Remission or Low Disease Activity.

OBJECTIVES: This study aimed to investigate the predictive value of synovitis and tenosynovitis detected by grayscale (GS) and by power Doppler (PD) ultrasound (US) in relation to failure of tapering disease-modifying antirheumatic drugs (DMARD) in rheumatoid arthritis (RA) patients. METHODS: Long-standing RA patients who de-escalated treatment were included in this prospective cohort study. All patients underwent 3 ultrasonographic and clinical assessments, at baseline and every 3 or 4 months, over a period of 6-8 months. US investigation of 32 joints was performed. Synovitis was assessed by GS and PD semiquantitative scoring (0-3) and a global score was calculated for each individual by summing single joint scores. The presence of tenosynovitis was recorded whenever detected during ultrasound assessment. RESULTS: Thirty-three patients completed the follow-up period (29 women; 4 men). Eight patients (25%) relapsed. Using the optimal cutoff values determined by receiver operating characteristic curve, patients with a PD synovitis ≥1 at baseline had significantly greater chances to relapse than those without PD activity. During follow-up, GS tenosynovitis was detected in 6 patients (5 with PD) who failed and in 3 patients (1 with PD) who succeeded in tapering therapy. Having at least 1 joint with PD synovitis resulted in a relative risk of 3.14 and having GS tenosynovitis resulted in a relative risk of 11.4 (95% CI: 1.03-9.60 and 2.82-45.9, respectively) for relapse in the multivariate Poisson model. CONCLUSIONS: PD synovitis and GS tenosynovitis may be useful to identify RA patients in risk of relapse after DMARD tapering.

Ultrasound Assessment of Disease Activity Prevents Disease-Modifying Antirheumatic Drug (DMARD) Escalation and May Reduce DMARD-Related Direct Costs in Rheumatoid Arthritis With Fibromyalgia: An Exploratory Study.

OBJECTIVES: as an objective measure, ultrasound (US) could prevent rheumatoid arthritis (RA) overtreatment induced by concomitant fibromyalgia (FM). Our goal was to study how patients with RA and FM who underwent a US examination differed from those without a US examination in terms of overall disease-modifying antirheumatic drug (DMARD) escalation and biologic DMARD-related direct costs. METHODS: Patients with RA and FM were seen between 2011 and 2017. In cases of 28-joint Disease Activity Score (DAS28) overestimation, patients were referred to undergo a US examination. The US group underwent a US examination to confirm disease activity, and the DAS28 group had disease activity assessment based solely on the DAS28. RESULTS: Of 230 patients with RA, 22 women with RA and FM (DAS28 group, n = 9; and US group, n = 13) were seen in 316 visits (115.68 patient-years). The DMARD treatment was escalated in 27.1% of visits in the DAS28 group versus 17.3% in the US group (P = .046). The relative risk of DMARD escalation in the DAS28 group compared to the US group was 1.57 (95% confidence interval, 1.01-2.43). In sum total, US$240,784.52 were spent on biologics throughout the entire study period. Basing biologic DMARD prescriptions on US results could save an average of US$405.66 per patient-year. CONCLUSIONS: In this real-life study of patients with RA and FM, a US examination was associated with less DMARD escalation and could reduce biologic DMARD direct costs. Specifically, synovitis as scored by power Doppler US could be useful as a treatment target for RA in patients with DAS28 overestimation due to FM, but further studies are necessary.

Vitamin D and Cytokine Profiles in Patients With Systemic Sclerosis.

INTRODUCTION: Hypovitaminosis D has been frequently described in systemic sclerosis (SSc). Cytokines are important mediators of tissue damage and clinical dysfunction in SSc and may be influenced by vitamin D levels. OBJECTIVE: To evaluate the serum levels of vitamin D and its correlation with the clinical features and cytokine profiles in SSc patients. METHODS: Case-control study, including 50 SSc patients and 35 healthy non matched controls. Serum levels of 25(OH) vitamin D were measured by chemiluminescence assay, and serum concentrations of interleukin 2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor, and interferon γ were determined by flow cytometry. RESULTS: Fourteen patients (28%) had diffuse cutaneous SSc, 94% were female, 80% European derived, with a mean age of 57.2 ± 12.8 years. The serum vitamin D levels in SSc patients were 23.9 ± 8.5 ng/mL and 30.2 ± 6.2 ng/mL in the control group (standardized mean difference -6.19; 95% confidence interval, -9.9 to -2.3; p = 0.002), despite the more frequent supplementation of vitamin D in SSc patients (p = 0.014). No significant associations were found among vitamin D concentrations and cytokine levels. Serum levels of IL-6 were significantly elevated in SSc patients (p = 0.024) and were positively correlated with the modified Rodnan skin score (rs = 0.291, p =0.041). CONCLUSIONS: Despite lower vitamin D levels in SSc patients, there was no clear association with any cytokine. Serum levels of IL-6 were significantly elevated and positively correlated with the extent of skin involvement in SSc patients.

Neuromuscular fatigue is weakly associated with perception of fatigue and function in patients with rheumatoid arthritis.

To assess electromyographic parameters of neuromuscular fatigue in knee extensors and their association with clinical, functional and emotional features in patients with rheumatoid arthritis (RA). Thirty-eight female patients with RA participated. Electromyography parameters (changes in signal amplitude, represented by the root mean square, and frequency content, represented by median frequency-MDF) were assessed during a submaximal (60%) isometric contraction of the knee extensors, sustained for 60 s. Clinical characteristics; the 28-joint Disease Activity Score (DAS-28) in which includes count of swollen joints (out of the 28) and tender joints (out of the 28), the erythrocyte sedimentation rate and global disease activity measured on a visual analogue scale; serum C reactive protein (CRP); information on treatment; the Health Assessment Questionnaire; the Functional Assessment of Chronic Illness Therapy fatigue scale (FACIT-F); the Short Form Health Survey (SF-36) and the International Physical Activity Questionnaire (IPAQ), were also assessed. The mean patient age was 51.0 ± 8.2 years, mean disease activity score was 11.5 ± 7.1, and mean CRP level was 8.0 ± 7.8 mg/dL. There was a moderate correlation between MDF and age (r = 0.5), as well as weak correlations of MDF with FACIT-F (r = 0.3), physical functioning (r = - 0.3) and vitality domains (r = - 0.3) of the SF-36, and IPAQ (r = - 0.3) (p ≤ 0.05 for all). No association was observed between electromyography measurements and clinical or treatment features. The electromyographic parameter MDF was correlated with perception of fatigue, age, physical functioning and vitality domains of SF-36, and physical activity level in this sample. These results indicate that primary muscle factors should also be considered when managing perceived fatigue in patients with RA.

Long-term outcomes of treat-to-target strategy in established rheumatoid arthritis: a daily practice prospective cohort study.

To examine disease activity and physical function after implementation of treat-to-target (T2T) strategy in patients with established rheumatoid arthritis (RA) over a long-term period. Patients with RA were started on a T2T strategy in 2005 and followed through 2014. Patients were seen every 3-4 months until remission/low disease activity was achieved and every 6 months thereafter. Disease activity was measured by the DAS28 and CDAI, and physical function by the HAQ-DI. Results were presented as all observed data, without imputation for missing values. Changes in disease activity and physical function were evaluated by generalized estimating equations (GEE). Two hundred and twenty-nine patients were included, with a mean (SD) disease duration of 10.6 (7.4) years. Significant improvements were seen in both composite scores during the follow-up period, as demonstrated by DAS28 (ß coefficient = 0.19; 95% CI = 0.16-0.21; p < 0.01) and by CDAI (ß coefficient = 1.59; 95% CI = 1.84-1.34; p < 0.01). Physical function also improved, as demonstrated by HAQ-DI (ß coefficient = 0.03; 95% CI = 0.02-0.04; p < 0.01). Biological therapy was associated with improvement in disease activity and in physical function. Leflunomide was only associated with improvement in physical function. Clinically meaningful reductions of DAS28, CDAI and HAQ-DI were observed in patients with established rheumatoid arthritis from 2005 to 2014. Implementation of new therapeutic options, in the scenario of T2T strategy, was associated with improvement in disease activity and physical function.

Assessment of muscle mass using chest computed tomography-based quantitative and qualitative measurements in patients with systemic sclerosis: A retrospective study with cross-sectional and longitudinal analyses.

BACKGROUND/ PURPOSE: Sarcopenia has been increasingly studied in systemic sclerosis (SSc), which is one of the most lethal autoimmune diseases, mainly due to lung involvement. Our objective was to study the associations of myopenia and/or myosteatosis with clinical features of SSc and subsequent adverse outcomes. METHODS: This is a retrospective study with cross-sectional and longitudinal analyses, in which patients with SSc were consecutively included in the outpatient clinic of a tertiary university hospital between 2012 and 2021. Clinical and laboratory parameters of patients with SSc were collected from their medical records. Skeletal muscle mass was assessed on chest computed tomography (CT) at the level of the first lumbar vertebra (L1) by skeletal muscle area (SMA), skeletal muscle index ([SMI] SMA/height2), and skeletal muscle radiation attenuation (SMRA). Cut-off values for myopenia in women and men were SMA <70.1 cm² and <110.4 cm², and SMI <25.9 cm²/m² and <34.6 cm²/m², respectively; values for myosteatosis in women and men were SMRA <29.8 HU and <36.3 HU, respectively. In a subgroup of 31 patients followed-up between 2017 and 2019, the diagnostic properties of SMA, SMI, and SMRA by CT were compared with the appendicular skeletal muscle mass index (ASMI) by dual-energy X-ray absorptiometry (DXA). Low muscle quantity was defined according to the European Working Group on Sarcopenia in Older People 2: ASMI <5.5 kg/m2 in women and <7.0 kg/m2 in men. Afterwards, a better tomographic index was used for correlating with clinical and laboratory parameters. RESULTS: Myopenia and/or myosteatosis were present in 75.7 % of patients with SSc. The prevalence rates according to each index were SMA 25.2%, SMI 12.1%, and SMRA 69.2%. In 73% of the patients with overweight/obesity (body mass index [BMI] ≥25 kg/m²), only SMRA was reduced. Considering ASMI as the gold standard, the sensitivity, specificity, positive and negative predictive values for SMA were 60%, 96.2%, 75% and 92.6%, respectively; for SMI, they were 40%, 96.2%, 66.7%, and 89.3%, respectively; for SMRA, these values were 60%, 34.6%, 15%, and 81.8%. Pearson's correlation coefficients were 0.73, 0.74, and 0.10 for SMA, SMI, and SMRA, respectively, and ASMI significantly agreed with SMA (kappa 0.611, p < 0.001) and SMI (kappa 0.431, p = 0.012). After adjustments in a multivariate model, BMI (p < 0.001) and female sex (p < 0.001) remained significantly associated with myopenia by SMA; BMI (p =0.010) remained significantly associated with low muscle mass by ASMI. CONCLUSION: The SMA index at L1 level on chest CT was demonstrated to be an accurate measure that is useful for detecting myopenia in patients with SSc. BMI and male sex predicted low SMA and BMI was associated with low ASMI on DXA. STATEMENT OF CLINICAL SIGNIFICANCE: In recent years, great advances have been made in sarcopenia-related research, resulting in broader knowledge on its definition, causes, diagnosis, and treatment options. Regarding the techniques used for assessing muscle composition, computed tomography (CT) was demonstrated by many studies to be an efficient and easy-to-use method that can be employed by professionals of different specialties, including rheumatologists. This study was able to demonstrate that although the L3 image was not present on CT, the analysis of SMA at the L1 level on chest CT proved to be an accurate and useful measure to detect myopenia in patients with SSc. This study identified some associated factors of myopenia and/or myosteatosis according to each method employed for assessing muscle composition. Reduced BMI and male sex were associated factors of myopenia when using SMA, and reduced BMI was associated with myopenia when employing ASMI by DXA. Finally, we highlight the need not to generalize the term "sarcopenia" in clinical studies assessing imaging parameters of body composition. The use of the terms myopenia and/or myosteatosis would be more adequate, because CT allows the assessment of muscle composition and not strength or physical performance.

Changes in physical function over time in rheumatoid arthritis patients: A cohort study.

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.

Physical frailty in patients with systemic sclerosis.

INTRODUCTION: Systemic sclerosis (SSc) is a chronic disease characterized by autoimmunity, vasculopathy and fibrosis of several organs, such as skin, lungs, and heart. During the disease course, patients with SSc are prone to accumulating multiple organ damage and increasing their vulnerability to adverse outcomes. This increased vulnerability to adverse outcomes when exposed to a stressor among people of the same age is known as frailty. One of the most used definitions of frailty is the physical frailty phenotype (PFP), including 5 components: unintentional weight loss, exhaustion, muscle weakness, slow walking speed, and low physical activity. There is scarce data about frailty in patients with SSc. OBJECTIVES: To determine the prevalence and clinical profile of PFP in a sample of patients with SSc. To investigate the diagnostic accuracy of the Fatigue, Resistance, Ambulation, Illness and Loss of weight (FRAIL) scale, Edmonton frailty scale (EFS) and Short Physical Performance Battery (SPPB) using the PFP as the reference standard. METHODS: Cross-sectional study including 94 patients with SSc according to the 2013 ACR-EULAR classification criteria or the criteria suggested by Le Roy and Medsger for early disease. Gastrointestinal symptoms were assessed by the UCLA GIT 2.0 questionnaire, malnutrition was defined according to European Society of Clinical Nutrition and Metabolism (ESPEN) recommendations, and physical performance was assessed by SPPB. PFP assessment was according to the original definition, except for physical activity domain, assessed with the International Physical Activity Questionnaire (IPAQ). FRAIL scale and EFS were also applied to the same individuals. For diagnostic assessment of FRAIL, EFS and SPPB, we estimated the area under the receiver operating characteristic curve (AUC), considering PFP as the reference standard and dichotomizing the results in frail vs. non-frail. RESULTS: According to PFP, 33 patients (35.1%) were considered frail and 53 patients (56.4%) pre-frail. According to FRAIL scale, 27 patients (28.7%) were considered frail and 53 patients (56.4%) pre-frail. According to EFS, 28 patients (29.7%) were classified as vulnerable and 15 (15.9%) as frail: mild in 8 (8.5%), moderate in 5 (5.3%) and severe in 2 (2.1%). According to SPPB, 19 patients (20.2%) were considered frail. The AUC against PFP was: 0.829 (95% CI 0.743-0.916) for FRAIL scale, 0.859 (95% CI 0.784-0.934) for EFS and 0.791 (95% CI 0.697-0.885) for SPPB. The PFP was associated with current use of glucocorticoids (p=0.011), UCLA GIT 2.0 score (p=0.001), HAQ (p<0.0001), patient and physician-assigned VAS (p<0.0001, both), malnutrition (p=0.007), hospitalizations in the past year (p=0.008) and dependence on BADL and IADL (p=0.027 and p<0.0001, respectively). The PFP was not associated with gender (p=0.679), age (p=0.303), disease duration (p=0.504), Rodnan skin score (p=0.918), diffuse subtype (p=0.116), polypharmacy (p=845) and sarcopenia (p=0.328). CONCLUSION: Frailty is prevalent in patients with long-standing SSc and is associated with disability, limitations in daily activities and hospitalizations in the past year. Also, malnutrition and more severe gastrointestinal symptoms were more common in frail patients. Both FRAIL scale and EFS showed excellent diagnostic accuracy against PFP as the reference standard, however the FRAIL scale presents a higher sensitivity and seems to be more feasible and practical than EFS and SPPB in clinical practice.

Dualities of the vitamin D in systemic sclerosis: a systematic literature review.

BACKGROUND: Systemic sclerosis (SSc) is a chronic disease characterized by autoimmunity, vasculopathy, and visceral and cutaneous fibrosis. Vitamin D has several functions in the immunological system, and different studies have suggested a potential role in triggering autoimmune diseases. Patients with SSc may present with low serum levels of vitamin D, but the association between hypovitaminosis D and disease onset or any clinical manifestation is still obscure. Our goal was to verify the causal relationship between hypovitaminosis D and SSc onset or any particular clinical manifestation in the literature. METHODS: A systematic literature review was performed through February 24th, 2021 on Pubmed, Lilacs/BIREME, and Cochrane databases. The eligible studies were read in full text, and, in the absence of exclusion criteria, were included in this review after consensus between two reviewers. RESULTS: Forty articles met the eligibility criteria and the main results of each study are described. In most studies, SSc patients showed a higher prevalence of vitamin D deficiency and insufficiency compared to controls. Additionally, in some reports serum levels of vitamin D were inversely correlated with the severity of SSc. Oral supplementation did not seem to affect serum levels of vitamin D. Four of the included studies were with experimental models. CONCLUSION: In conclusion, vitamin D deficiency seems to have a role in susceptibility to SSc, as well as in the clinical manifestations of the disease.

Ultrasonographic and resistance index evaluation of nails in psoriatic arthritis, psoriasis, and control groups: a cross-sectional study.

BACKGROUND: Nail psoriasis occurs frequently in patients with psoriatic disease, it can lead to functional impairment, pain, discomfort, decreased quality of life and can also be a predictor for the development of arthritis. Early recognition of this condition can provide early and effective treatment and prevent structural impairment. This study aims to identify nail ultrasonographic characteristics in three groups: psoriasis (PsO), psoriatic arthritis (PsA) and controls patients, to determine if the ultrasonography (US) can identify early signs of nail psoriatic impairment or local inflammation. We conducted nail US to determine nail matrix resistance index (NMRI), nail bed resistance index (NBRI), and power Doppler (PD) and grayscale (GS) parameters in these 3 groups. METHODS: Single-center, cross-sectional study. GS, PD, and spectral doppler images of bilateral 2nd and 3rd fingernails were acquired from 35 PsO, 31 PsA, and 35 controls patients. An US equipment with an 18 MHz linear transducer for GS and 8.0 MHz for PD was used. PD, NMRI, NBRI, nail plate thickness (NPT), nail bed thickness (NBT), nail matrix thickness (NMT), and morphostructural characteristics of the trilaminar structure (TS) were evaluated in saved images, blind. RESULTS: Mean NMRI and NBRI did not differ between groups. Linear regression analysis detected no relationships between PsO or PsA and NMRI or NBRI. Nail PD grade did not differ between groups. Type I and IV TS changes were more frequent in PsO; types II and III changes were more frequent in PsA (p < 0.001). NPT was greater in PsA and PsO groups than controls: PsA 0.73 ± 0.14 mm, PsO 0.72 ± 0.15 mm, Controls 0.67 ± 0.10 mm (p = 0.001). CONCLUSION: Echographic TS characteristics of the nail plate and NPT evaluated by GS are useful and can distinguish PsO and PsA nails from controls. NMRI, NBRI, and US nail microcirculation parameters could not distinguish psoriatic nails. TRIAL REGISTRATION: 72762317.4.0000.5327 (Certificate of Presentation of Ethical Appreciation - CAAE - Plataforma Brasil) Avaiable in  https://plataformabrasil.saude.gov.br/login.jsf .

Flow cytometry evaluation of CD14/CD16 monocyte subpopulations in systemic sclerosis patients: a cross sectional controlled study.

BACKGROUND: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by vasculopathy and fibrosis, which can be subclassified into diffuse cutaneous (dSSc) and limited cutaneous (lSSc) subtypes. Previous studies suggest that an increase in monocytes can be a hallmark of various inflammatory diseases, including SSc. Our aim was to evaluate circulating blood monocyte subpopulations (classical, intermediate and non-classical) of SSc patients and their possible association with disease manifestations. METHODS: Fifty consecutive patients fulfilling the 2013 ACR/EULAR classification criteria for SSc were included in a cross-sectional study. Monocyte subpopulations were identified based on their expression of CD64, CD14 and CD16, evaluated by flow cytometry, and were correlated with the clinical characteristics of the patients; furthermore, the expression of HLA-DR, CD163, CD169 and CD206 in the monocytes was studied. Thirty-eight age- and sex-matched healthy individuals were recruited as a control group. RESULTS: SSc patients had an increased number of circulating peripheral blood monocytes with an activated phenotypic profile compared to healthy subjects. Absolute counts of CD16+ (intermediary and non-classical) monocyte subpopulations were higher in SSc patients. There was no association between monocyte subpopulations and the clinical manifestations evaluated. CONCLUSION: We identified higher counts of all monocyte subpopulations in SSc patients compared to the control group. There was no association between monocyte subpopulations and major fibrotic manifestations. CD169 was shown to be more representative in dSSc, being a promising marker for differentiating disease subtypes.

The effects of resistance training with blood flow restriction on muscle strength, muscle hypertrophy and functionality in patients with osteoarthritis and rheumatoid arthritis: A systematic review with meta-analysis.

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.

Morphological Parameters in Quadriceps Muscle Were Associated with Clinical Features and Muscle Strength of Women with Rheumatoid Arthritis: A Cross-Sectional Study.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune, inflammatory and chronic disease that may lead to loss of muscle mass, muscle strength and decreased functionality. Our objectives are to assess the quadriceps muscle morphology by ultrasound (MU) and verify its associations with clinical features, muscle strength and physical function in RA patients. METHODS: In this cross-sectional study, RA women (≥18 years) were included. Morphological parameters in quadriceps muscle consisted of the muscle thickness and pennation angle of rectus femoris (RF), vastus intermedius (VI) and vastus lateralis (VL). RA activity was measured by a 28-joint disease activity score (DAS28), muscle strength by handgrip and chair stand tests, and physical function by health assessment questionnaire (HAQ), timed-up-and-go (TUG) test and short physical performance battery (SPPB). RESULTS: Fifty-five patients were included (age: 56.73 ± 9.46 years; DAS28: 3.08 ± 1.29). Muscle thickness in RF, VI and VL were negatively associated with age (RF, p < 0.001; VI, p = 0.013; VL, p = 0.002) and disease duration (RF, p < 0.001; VI, p = 0.005; VL, p = 0.001), and were positively associated with handgrip strength (RF, p = 0.015; VI, p = 0.022; VL, p = 0.013). In addition, decreased muscle thickness in VI (p = 0.035) and a smaller pennation angle in RF (p = 0.030) were associated with higher DAS-28 scores. CONCLUSION: Quadriceps muscle morphology by ultrasound appears to be affected by age, disease duration, disease activity and muscle strength in patients with RA. MU can be a useful method to evaluate the impact of the disease on skeletal muscle.

Practical screening tools for sarcopenia in patients with systemic sclerosis.

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.

Incidence of tuberculosis in patients receiving anti-TNF therapy for rheumatic diseases: a systematic review.

INTRODUCTION: The TNF inhibitors were the first immunobiologicals used to treat rheumatic diseases, but their use is associated with an increased risk of tuberculosis. The primary objective is to estimate the incidence of tuberculosis in patients with rheumatic diseases exposed to anti-TNF therapy. The secondary objectives are to evaluate the incidence of tuberculosis by region and subgroups of diseases, to review the presentation of tuberculosis in these patients, and to assess the time elapsed between onset of anti-TNF therapy and development of active granulomatous disease. METHODS: A systematic review of the literature was conducted in MEDLINE, the Cochrane Library, and LILACS. The primary endpoint was described as incidence and secondary outcomes, through subgroup analyses and comparisons of means. RESULTS: We included 52 observational studies. Among the exposed patients, 947 cases of tuberculosis were documented (62.2% pulmonary), with a cumulative incidence of 9.62 cases per 1000 patients exposed. TB incidence across different continents was distributed as follows: South America, 11.75 cases/1000 patients exposed; North America, 4.34 cases/1000 patients exposed; Europe, 6.28 cases/1000 patients exposed; and Asia, 13.47 cases/1000 patients exposed. There were no significant differences in TB incidence among the described diseases. The mean time elapsed from start of anti-TNF therapy until the endpoint was 18.05 months. CONCLUSION: The incidence of TB in patients with rheumatic diseases exposed TNF inhibitor considering all countries was 9.62 cases per 1000 patients exposed. TB incidence was higher in South America and Asia compared with North America and Europe. Most cases occurred in the first XX months of use, and the pulmonary form predominated.Key Points• Higher incidence of tuberculosis in patients exposed to anti-TNF compared with the general population.• Higher incidence of TB in countries of South America and Asia compared with North America and Europe.

Prevalence of Psoriatic Arthritis Patients Achieving Minimal Disease Activity in Real-world Studies and Randomized Clinical Trials: Systematic Review with Metaanalysis.

OBJECTIVE: To estimate the frequency of patients with psoriatic arthritis (PsA) achieving minimal disease activity (MDA) status in real-world studies and randomized controlled trials (RCT). METHODS: A systematic literature search for 2009-2017 was performed in PubMed, Embase, Cochrane Library, and LILACS. Study selection and data extraction were performed by 2 independent researchers. Random-effects single-arm metaanalyses were performed and heterogeneity was assessed using I2. RESULTS: A total of 405 records were identified and 45 studies were analyzed: 39 (86.7%) observational studies and 6 (13.3%) RCT; they included 12,469 patients. The overall prevalence of MDA in cross-sectional studies was 35% (95% CI 30%-41%, I2 = 94%), varying from 17% (95% CI 7%-34%) in patients taking synthetic disease-modifying antirheumatic drugs (DMARD) to 57% (95% CI 41%-71%) in those taking biological DMARD. Prevalence of MDA in cohort studies increased with longer followup time, ranging from 25% (95% CI 15%-40%) with 3- to 4-month followup to 42% (95% CI 38%-45%) with > 24-month followup. Patients with PsA receiving biological DMARD in a real-world context and RCT had similar prevalence of MDA at 6-month followup: 30% (95% CI 21%-41%, I2 = 85%) versus 32% (95% CI 26%-39%, I2 = 79%), respectively. CONCLUSION: Patients with PsA included in real-world studies had similar prevalence of MDA compared to those in controlled clinical trials. This finding suggests that MDA is a useful treatment target for PsA in the real-world setting.

Cachexia in patients with rheumatoid arthritis: a cohort study.

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.

A population-based study of tuberculosis incidence among rheumatic disease patients under anti-TNF treatment.

INTRODUCTION: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. The advent of immunobiologic therapy with TNF inhibitors agents, has been associated with a significant increase in incident cases of tuberculosis in this population. OBJECTIVE: To estimate the incidence of tuberculosis in patients receiving TNF inhibitors therapy for rheumatic diseases. As secondary objectives, we sought to evaluate mortality and the clinical impact of screening for latent tuberculosis infection. METHODS: This retrospective study included patients with rheumatic diseases of Public Health System from the Brazilian state, a high TB incidence area, who received prescriptions of TNF inhibitors agents between 2006 and 2016. RESULTS: A total of 5853 rheumatic disease patients were included. Patients were predominantly women (68.7%) aged 49.5 (± 14.7) years old. Forty-three cases of TB were found (2.86 cases per 1000 person-years; 18 times higher than in the general population). Adalimumab and certolizumab users presented a higher risk for TB development compared to etanercept users (RR: 3.11, 95%CI 1.16-8.35; 7.47, 95%CI 1.39-40.0, respectively). In a subgroup of patients, screening for latent tuberculosis infection was performed in 86% of patients, and 30.2% had a positive tuberculin skin test. Despite latent TB treatment, TB was diagnosed in 2 out of 74 (2.7%) patients. Overall, TB diagnosis did not increase mortality. CONCLUSION: In this population-based study of rheumatic disease patients from a high incident area, TNF inhibitor exposure was associated with an 18-time increased TB incidence. Adalimumab and certolizumab were associated with greater and earlier TB diagnosis compared to etanercept.