Damaged bone microarchitecture by Trabecular Bone Score (TBS) and low appendicular muscle mass: main risk factors for vertebral and non-vertebral fractures in women with long-standing rheumatoid arthritis.

We ascertained the fracture risk factors stratified by vertebral and non-vertebral sites in rheumatoid arthritis (RA) females. Bone/muscle features, but not disease activity, were the main markers for fractures in this long-standing RA population: low trabecular bone score (TBS) for vertebral fracture and decreased appendicular muscle mass for non-vertebral fracture. PURPOSE: To assess risk factors for fractures, including clinical, laboratory and dual energy X-ray absorptiometry (DXA) parameters (bone mass, trabecular bone score-TBS, muscle mass) in women with established rheumatoid arthritis (RA). METHODS: Three hundred females with RA (ACR, 2010) were studied. Clinical data were obtained by questionnaire and disease activity by composite indices (DAS28, CDAI, SDAI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Bone mineral density (BMD), TBS, body composition and Vertebral Fracture Assessment (VFA) were performed by DXA. Logistic regression models were constructed to identify factors independently associated with vertebral (VF) and non-vertebral fractures (NVF), separately. RESULTS: Through rigorous eligibility criteria, a total of 265 women were yielded for final data analysis (median age, 55 [22-86] years; mean disease duration, 16.2 years). Prevalence of VF and NVF were 30.6% and 17.4%, respectively. In multivariate analyzes, TBS (OR = 1.6, 95%CI = 1.09-2.36, p = 0.017), CRP (OR = 1.54, 95%CI = 1.15-2.08, p = 0.004), and parathormone (OR = 1.24, 95%CI = 1.05-1.45, p = 0.009) were risk factors for VF, whereas low appendicular muscle mass (OR = 2.71; 95%CI = 1.01-7,28; p = 0.048), body mass index (BMI) (OR = 0.90, 95%CI = 0.82-0.99; p = 0.025), ESR (OR = 1.18, 95%CI = 1.01-1,38, p = 0,038) and hip BMD (OR = 1.82, 95%CI = 1.10-3.03, p = 0.02) were associated with NVF. CONCLUSION: In women with long-term RA, markers of fractures differed between distinct skeletal sites (vertebral and non-vertebral). The magnitude of association of bone/muscle parameters with fracture (TBS for VF and appendicular muscle mass for NVF) was greater than that of the association between RA activity and fracture. TBS seems to have greater discriminative power than BMD to identify subjects with VF in long-standing RA.

Scleromalacia perforans as an early manifestation of late-onset rheumatoid arthritis: a case-based review.

Rheumatoid arthritis is a chronic autoimmune disease that can affect different organs beyond the joints. Ocular involvement includes keratoconjunctivitis sicca, peripheral ulcerative keratitis (PUK), episcleritis, scleritis, anterior uveitis, and corneal impairment. The most severe form of scleritis, scleromalacia perforans, is an aggressive ophthalmic manifestation that can potentially lead to blindness, usually occurring in late stages of disease. We report a case of an elderly woman in which this severe ocular manifestation occurred early on disease onset, differing from most of the previously reported cases of scleromalacia perforans. Ocular symptoms started concomitantly with the polyarthritis and other extra-articular manifestations, including rheumatoid nodules and vasculitic skin lesions. Ocular disease progressed due to patient's loss to follow-up, requiring pulse therapy with methylprednisolone. However, despite treatment, right eye enucleation was required due to melting of the corneal patch with uveal exposition. The patient was then treated with rituximab with improvement of systemic disease. The present case reinforces that, although rare, this complication is severe and must be promptly diagnosed and aggressively treated to improve prognosis of ocular and systemic RA.

Two-week methotrexate discontinuation in patients with rheumatoid arthritis vaccinated with inactivated SARS-CoV-2 vaccine: a randomised clinical trial.

OBJECTIVE: To evaluate the effect on immunogenicity and safety of 2-week methotrexate (MTX) discontinuation after each dose of the Sinovac-CoronaVac vaccine versus MTX maintenance in patients with rheumatoid arthritis (RA). METHODS: This was a single-centre, prospective, randomised, investigator-blinded, intervention study (NCT04754698, CoronavRheum) including adult patients with RA (stable Clinical Disease Activity Index (CDAI) ≤10, prednisone ≤7.5 mg/day) randomised (1:1) to withdraw MTX (MTX-hold) for 2 weeks after each vaccine dose or maintain MTX (MTX-maintain), evaluated at day 0 (D0), D28 and D69. Coprimary outcomes were anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC) and neutralising antibody (NAb) positivity at D69. Secondary outcomes were geometric mean titres (GMT) and flare rates. For immunogenicity analyses, we excluded patients with baseline positive IgG/NAb, and for safety reasons those who flared at D28 (CDAI >10) and did not withdraw MTX twice. RESULTS: Randomisation included 138 patients with 9 exclusions (5 COVID-19, 4 protocol violations). Safety evaluation included 60 patients in the MTX-hold and 69 patients in the MTX-maintain group. Further exclusions included 27 patients (13 (21.7%) vs 14 (20.3%), p=0.848) with positive baseline IgG/NAb and 10 patients (21.3%) in MTX-hold with CDAI >10 at D28. At D69, the MTX-hold group (n=37) had a higher rate of SC than the MTX-maintain group (n=55) (29 (78.4%) vs 30 (54.5%), p=0.019), with parallel augmentation in GMT (34.2 (25.2-46.4) vs 16.8 (11.9-23.6), p=0.006). No differences were observed for NAb positivity (23 (62.2%) vs 27 (49.1%), p=0.217). At D28 flare, the rates were comparable in both groups (CDAI, p=0.122; Disease Activity Score in 28 joints with C reactive protein, p=0.576), whereas CDAI >10 was more frequent in MTX-hold at D69 (p=0.024). CONCLUSION: We provided novel data that 2-week MTX withdrawal after each dose of the Sinovac-CoronaVac vaccine improves anti-SARS-CoV-2 IgG response. The increased flare rates after the second MTX withdrawal may be attributed to the short-term interval between vaccine doses. This strategy requires close surveillance and shared decision making due to the possibility of flares.

Distinct impact of DMARD combination and monotherapy in immunogenicity of an inactivated SARS-CoV-2 vaccine in rheumatoid arthritis.

OBJECTIVES: To evaluate the distinct impact of disease modifying antirheumatic drugs (DMARD) combination and monotherapy in immune response to an inactivated SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA). METHODS: This phase 4 prospective study analysed seroconversion (SC) of anti-SARS-CoV-2 immunoglobulin G (IgG) and neutralising antibodies (NAb) induced by the inactivated vaccine (CoronaVac) in patients with RA in comparison to controls (CG). Disease activity and treatment were also assessed. Only participants with baseline negative IgG/NAb were included. RESULTS: Patients with RA (N=260) and CG (N=104) had comparable median ages (59 years (50-65 years) vs 58 years (49.8-64 years), p=0.483). Patients with RA had moderate but lower SC (61.8% vs 94.2%, p<0.001) and NAb positivity (45% vs 78.6%, p<0.001) in comparison to CG after full vaccination. Baseline disease activity did not influence immunogenicity (p>0.05). After multivariate analyses, factors independently related to reduced SC were: older age (OR=0.79 (0.70-0.89) for each 5-year interval, p<0.001), methotrexate (OR=0.54 (0.29-0.98), p=0.044), abatacept (OR=0.37 (0.19-0.73), p=0.004) and number of DMARD (OR=0.55 (0.33-0.90), p=0.018). Regarding NAb, age (OR=0.87 (0.78-0.96) for each 5-year interval, p=0.007) and prednisone >7.5 mg/day (OR=0.38 (0.19-0.74), p=0.004) were negatively related to the presence of NAb. Further comparison of SC/NAb positivity among RA treatment subgroups and CG revealed that methotrexate/tofacitinib/abatacept/tocilizumab use, in monotherapy or in combination, resulted in lower responses (p<0.05), while tumour necrosis factor inhibitor and other conventional synthetic DMARD interfered solely when combined with other therapies. CONCLUSIONS: Patients with RA under DMARD have a moderate immunogenicity to CoronaVac. We identified that nearly all DMARD combinations have a deleterious effect in immunogenicity, whereas a more restricted number of drugs (methotrexate/tofacitinib/abatacept/tocilizumab) also hampered this response as monotherapy. These findings reinforce the need of a broader approach, not limited to specific drugs, to improve vaccine response for this population. TRIAL REGISTRATION DETAILS: NCT04754698.

Reliability assessment of the definition of ultrasound enthesitis in SpA: results of a large, multicentre, international, web-based study.

OBJECTIVES: To investigate the reliability of the OMERACT US Task Force definition of US enthesitis in SpA. METHODS: In this web exercise, based on the evaluation of 101 images and 39 clips of the main entheses of the lower limbs, the elementary components included in the OMERACT definition of US enthesitis in SpA (hypoechoic areas, entheseal thickening, power Doppler signal at the enthesis, enthesophytes/calcifications, bone erosions) were assessed by 47 rheumatologists from 37 rheumatology centres in 15 countries. Inter- and intra-observer reliability of the US components of enthesitis was calculated using Light's kappa, Cohen's kappa, Prevalence And Bias Adjusted Kappa (PABAK) and their 95% CIs. RESULTS: Bone erosions and power Doppler signal at the enthesis showed the highest overall inter-reliability [Light's kappa: 0.77 (0.76-0.78), 0.72 (0.71-0.73), respectively; PABAK: 0.86 (0.86-0.87), 0.73 (0.73-0.74), respectively], followed by enthesophytes/calcifications [Light's kappa: 0.65 (0.64-0.65), PABAK: 0.67 (0.67-0.68)]. This was moderate for entheseal thickening [Light's kappa: 0.41 (0.41-0.42), PABAK: 0.41 (0.40-0.42)], and fair for hypoechoic areas [Light's kappa: 0.37 (0.36-0.38); PABAK: 0.37 (0.37-0.38)]. A similar trend was observed in the intra-reliability exercise, although this was characterized by an overall higher degree of reliability for all US elementary components compared with the inter-observer evaluation. CONCLUSIONS: The results of this multicentre, international, web-based study show a good reliability of the OMERACT US definition of bone erosions, power Doppler signal at the enthesis and enthesophytes/calcifications. The low reliability of entheseal thickening and hypoechoic areas raises questions about the opportunity to revise the definition of these two major components for the US diagnosis of enthesitis.

Performance of the Rheumatoid Arthritis Disease Activity Index in the Assessment of Disease Activity in Rheumatoid Arthritis-Findings From the REAL Study.

BACKGROUND/OBJECTIVE: Although telemedicine use has been under discussion for decades, this topic has gained unprecedented importance during the COVID-19 pandemic. The Rheumatoid Arthritis Disease Activity Index (RADAI) is a user-friendly tool, fully self-administered, to assess rheumatoid arthritis (RA) disease activity. The aim of this study was to compare the performance of RADAI with other disease activity indices, functional status, and inflammatory markers in a large cohort of RA patients. METHODS: We assessed the concurrent validity of RADAI against Clinical Disease Activity Index (CDAI), Disease Activity Score in 28 Joints-C-reactive protein, Disease Activity Score in 28 Joints-erythrocyte sedimentation rate, Simplified Disease Activity Index, and physician assessment of disease activity and the correlation of RADAI with Health Assessment Questionnaire-Disability Index and inflammatory markers at the REAL Study baseline. We also evaluated the correlation of the change in RADAI and the change in CDAI over a 6-month follow-up. RESULTS: From the 1115 patients included in the REAL Study, 1113 had RADAI scores in the first assessment. At baseline, correlations between RADAI and other disease activity indices were strong, ranging from 0.64 (comparison with physician assessment) to 0.79 (comparison with CDAI). Correlation between the change in RADAI score over the 6 months of follow-up and the change in CDAI score over the same period was moderate/strong for the overall group and within the stratified analyses. CONCLUSION: The strong correlation of RADAI with other well-established tools for disease activity measurement reassures its use with RA patients' follow-up, especially in this new era of telemedicine.

Increased sympathetic and haemodynamic responses to exercise and muscle metaboreflex activation in post-menopausal women with rheumatoid arthritis.

KEY POINTS: Rheumatoid arthritis (RA) patients present exacerbated blood pressure responses to exercise, but little is known regarding the underlying mechanisms involved.  This study assessed autonomic and haemodynamic responses to exercise and to the isolated activation of muscle metaboreflex in post-menopausal women with RA.  Participants with RA showed augmented pressor and sympathetic responses to exercise and to the activation of muscle metaboreflex. These responses were associated with multiple pro- and anti-inflammatory cytokines and with pain.  The results of the present study support the suggestion that an abnormal reflex control of circulation is an important mechanism underlying the exacerbated cardiovascular response to exercise and increased cardiovascular risk in RA. ABSTRACT: Studies have reported abnormal cardiovascular responses to exercise in rheumatoid arthritis (RA) patients, but little is known regarding the underlying mechanisms involved. This study assessed haemodynamic and sympathetic responses to exercise and to the isolated activation of muscle metaboreflex in women diagnosed with RA. Thirty-three post-menopausal women diagnosed with RA and 10 matched controls (CON) participated in this study. Mean arterial pressure (MAP), heart rate (HR) and muscle sympathetic nerve activity (MSNA frequency and incidence) were measured during a protocol of isometric knee extension exercise (3 min, 30% of maximal voluntary contraction), followed by post-exercise ischaemia (PEI). Participants with RA showed greater increases in MAP and MSNA during exercise and PEI than CON (ΔMAPexercise  = 16 ± 11 vs. 9 ± 6 mmHg, P = 0.03; ΔMAPPEI  = 15 ± 10 vs. 5 ± 5 mmHg, P = 0.001; ΔMSNAexercise  = 17 ± 14 vs. 7 ± 9 bursts min-1 , P = 0.04; ΔMSNAPEI  = 14 ± 10 vs. 6 ± 4 bursts min-1 , P = 0.04). Autonomic responses to exercise showed significant (P < 0.05) association with pro- (i.e. IFN-γ, IL-8, MCP-1 and TNFα) and anti-inflammatory (i.e. IL-1ra and IL-10) cytokines and with pain. In conclusion, post-menopausal women with RA showed augmented pressor and sympathetic responses to exercise and to the activation of muscle metaboreflex. These findings provide mechanistic insights that may explain the abnormal cardiovascular responses to exercise in RA.

Methotrexate and rheumatoid arthritis associated interstitial lung disease.

QUESTION ADDRESSED BY THE STUDY: Methotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Fibrotic interstitial lung disease (ILD) is a common complication of RA. Whether MTX exposure increases the risk of ILD in patients with RA is disputed. We aimed to evaluate the association of prior MTX use with development of RA-ILD. METHODS: Through a case-control study design with discovery and international replication samples, we examined the association of MTX exposure with ILD in 410 patients with chronic fibrotic ILD associated with RA (RA-ILD) and 673 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques. RESULTS: Analysis of the discovery sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted OR 0.46, 95% CI 0.24-0.90; p=0.022), which was confirmed in the replication samples (pooled adjusted OR 0.39, 95% CI 0.19-0.79; p=0.009). The combined estimate using both the derivation and validation samples revealed an adjusted OR of 0.43 (95% CI 0.26-0.69; p=0.0006). MTX ever-users were less frequent among patients with RA-ILD compared to those without ILD, irrespective of chest high-resolution computed tomography pattern. In patients with RA-ILD, ILD detection was significantly delayed in MTX ever-users compared to never-users (11.4±10.4 years and 4.0±7.4 years, respectively; p<0.001). ANSWER TO THE QUESTION: Our results suggest that MTX use is not associated with an increased risk of RA-ILD in patients with RA, and that ILD was detected later in MTX-treated patients.

Changes to Body Composition in Women With Long-Standing Established Rheumatoid Arthritis: Differences by Level of Disease Activity.

INTRODUCTION: Few studies on rheumatoid arthritis have investigated disease activity and body composition by dual-energy X-ray absorptiometry including evaluation of visceral adipose tissue. Thus, we sought to verify the association between body composition by dual-energy X-ray absorptiometry, including visceral adipose tissue, and inflammatory activity in long-standing established rheumatoid arthritis. METHODS: Seventy-eight postmenopausal women with rheumatoid arthritis (American College of Rheumatology 2010) were studied. Disease activity was assessed by composite indexes (DAS28, CDAI, SDAI) and C-reactive protein. Potential association between body composition and disease activity was analysed by Pearson correlation and Tukey´s test (p < 0.05). RESULTS: There was significant negative correlation between C-reactive protein and appendicular lean mass index (r = -0.234, p = 0.039). After adjusting for confounding variables, women with C-reactive protein >10 mg/L had a lower appendicular lean mass index than those with C-reactive protein 5-10 mg/L and <5 mg/L (6.3 ± 0.8 kg/m2 vs 7.2 ± 1.2 kg/m2 vs 6.8 ± 1.0 kg/m2, respectively; p = 0.013). Women with moderate inflammation (C-reactive protein 5-10 mg/L) had more fat than those with C-reactive protein >10 mg/L and C-reactive protein <5 mg/L (12.4 ± 3.5 kg/m2 vs 9.9 ± 3.6 kg/m2 vs 10.5 ± 2.8 kg/m2, respectively; p = 0.040), as well as more visceral adipose tissue than women with higher and lower C-reactive protein (812.5 ± 266.4 cm3 vs 604.3 ± 236.3cm3 vs 658.9 ± 255.6 cm3; p = 0.009). CONCLUSIONS: High inflammatory activity that persists after a long disease duration was associated with both lower muscle and fat mass (including visceral adipose tissue), which is suggestive of more exuberant rheumatoid cachexia. Conversely, moderate activity was associated with greater visceral adipose tissue, which is associated with increased cardiovascular risk. These results point to the existence of different body composition profiles according to inflammatory status and the importance of individualized approaches to muscle mass and adiposity according to disease activity level in long-standing rheumatoid arthritis.

Chronotropic Incompetence and Reduced Heart Rate Recovery in Rheumatoid Arthritis.

BACKGROUND/OBJECTIVE: Recent studies have indicated that cardiac autonomic dysfunction is an early sign of cardiovascular impairment in rheumatoid arthritis (RA). Previous studies have mainly focused on resting assessments; however, analysis of heart rate (HR) responses to exercise might provide additional information on cardiac autonomic dysfunction in this disease. Thus, we aimed to assess the HR responses during and after a maximal graded exercise test in patients with RA and healthy controls (CONs). METHODS: This was a cross-sectional study in which 27 female RA patients and 14 female CONs frequency matched by physical activity, age, and body mass index were compared for HR responses during and after a maximal graded exercise test. RESULTS: Rheumatoid arthritis patients showed reduced chronotropic response (94.3% ± 16.3% vs. 106.1% ± 10.3%, p = 0.02) and lower HR recovery (HRR) at 30 seconds (8.6 ± 6.7 vs. 13.4 ± 5.2 beats/min [bpm], p = 0.02), 60 seconds (16.5 ± 7.8 vs. 24.0 ± 9.9 bpm, p = 0.01), 120 seconds (32.6 ± 9.9 vs. 40.7 ± 12.3 bpm, p = 0.03), and 180 seconds (46.5 ± 12.6 vs. 55.5 ± 13.4 bpm, p = 0.05) post-maximal exercise test when compared with CONs. Moreover, the prevalence of chronotropic incompetence (i.e., failure to reach 80% of the HR-predicted response) and abnormal HRR (i.e., HRR ≤12 bpm) were, respectively, 22.2% and 37.1% in RA patients. CONCLUSIONS: Patients with RA showed reduced chronotropic response to exercise and slower postexercise HRR. These abnormal autonomic responses to exercise indicate the presence of cardiac autonomic dysfunction and increased cardiovascular risk in this population.

Bone erosions in rheumatoid arthritis: ultrasound findings in the early stage of the disease.

OBJECTIVE: The objective of this study was to determine the prevalence and distribution of bone erosions detectable by US in patients with early RA (ERA) in comparison with long-standing RA (LSRA), other erosive diseases and healthy controls. METHODS: Thirty patients with ERA and 80 patients with LSRA were consecutively recruited. Thirty patients with PsA, 15 with primary OA, 10 with gout and 20 healthy subjects were included as controls. Bone erosions were investigated at the following anatomical sites: the second and fifth metacarpal heads, the ulnar head and the first and fifth metatarsal heads, bilaterally. Dorsal, volar and lateral aspects were explored on longitudinal and transverse views. RESULTS: At least one US bone erosion was found in 20 (66.7%) of 30 patients with ERA and in 10 (33%) of them it was found on the fifth metatarsal head. Bone erosions were most frequently found on the lateral quadrants of all scanned anatomical sites. If the second and fifth metacarpal heads and the fifth metatarsal head were scanned, an erosive disease could be found in 60% of ERA patients. The first metatarsal head was most frequently involved in the disease control group. CONCLUSION: This study found a high percentage of ERA patients with US bone erosions, with the fifth metatarsal head and the lateral aspects the most frequently involved site and quadrants. US scanning for bone erosions on a few target joints was found feasible and provided information not obtainable with clinical examination.

Ultrasonographic Insights into Peripheral Psoriatic Arthritis: Updates in Diagnosis and Monitoring.

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis, characterized by heterogeneous clinical manifestations and variable disease progression. Ultrasonography has emerged as a valuable tool in the diagnosis and monitoring of PsA, providing real-time visualization of joint and soft tissue abnormalities. This review highlights recent advancements in ultrasonographic techniques for the assessment of PsA, including the identification of typical features, the role of power Doppler imaging in detecting active inflammation, and the potential of ultrasound for guiding treatment decisions. Additionally, we discuss the utility of ultrasound in assessing treatment response and monitoring disease progression in patients with PsA, with a focus on novel imaging modalities. By elucidating the evolving role of ultrasonography in PsA management, this article aims to enhance clinicians' understanding of its utility in facilitating early diagnosis, optimizing treatment strategies, and improving patient outcomes.

A single session of aerobic exercise reduces systolic blood pressure at rest and in response to stress in women with rheumatoid arthritis and hypertension.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by increased risk of cardiovascular disease and hypertension (HT). A single session of aerobic exercise may reduce blood pressure (BP) in different clinical groups; however, little is known about the acute effects of exercise on BP in RA patients. This is a randomized controlled crossover study that assessed the effects of a single session of aerobic exercise on resting BP, on BP responses to stressful stimuli, and on 24-h BP in women with RA and HT. Twenty women with RA and HT (53 ± 10 years) undertook sessions of 30-min treadmill exercise (50% VO2max) or control (no exercise) in a crossover fashion. Before and after the sessions, BP was measured at rest, and in response to the Stroop-Color Word Test (SCWT), the Cold Pressor Test (CPT), and an isometric handgrip test. After the sessions, participants were also fitted with an ambulatory BP monitor for the assessment of 24-h BP. A single session of exercise reduced resting systolic BP (SBP) (-5 ± 9 mmHg; p < 0.05), and reduced SBP response to the SCWT (-7 ± 14 mmHg; p < 0.05), and to the CPT (-5 ± 11 mmHg; p < 0.05). Exercise did not reduce resting diastolic BP (DBP), BP responses to the isometric handgrip test or 24-h BP. In conclusion, a single session of aerobic exercise reduced SBP at rest and in response to stressful stimuli in hypertensive women with RA. These results support the use of exercise as a strategy for controlling HT and, hence, reducing cardiovascular risk in women with RA.Clinical Trial Registration: This study registered at the Brazilian Clinical Trials ( https://ensaiosclinicos.gov.br/rg/RBR-867k9g ) at 12/13/2019.

Predictors of serious infections in rheumatoid arthritis-a prospective Brazilian cohort.

BACKGROUND: Infections increase mortality and morbidity and often limit immunosuppressive treatment in rheumatoid arthritis patients. OBJECTIVE: To analyze the occurrence of serious infections and the associated factors in a cohort of rheumatoid arthritis patients under real-life conditions. METHODS: We analyzed data from the REAL, a prospective observational study, that evaluated Brazilian RA patients, with clinical and laboratory data collected over a year. Univariate and multivariate analyses were performed from the adjustment of the logistic regression model Generalized Estimating Equations (GEE), with the primary outcome being the occurrence of serious infection, defined as need for hospitalization or use of intravenous antibiotics for its treatment. RESULTS: 841 patients were included with an average follow-up time of 11.2 months (SD 2.4). Eighty-nine serious infections occurred, corresponding to 13 infections per 100 patient-years. Pulmonary fibrosis, chronic kidney disease (CKD) and central nervous system disease increased the chances of serious infection by 3.2 times (95% CI: 1.5-6.9), 3.6 times (95% CI: 1.2-10.4) and 2.4 times (95% CI: 1.2-5.0), respectively. The use of corticosteroids in moderate doses increased the chances by 5.4 times (95% CI: 2.3-12.4), and for each increase of 1 unit in the health assessment questionnaire (HAQ), the chance increased 60% (95% CI: 20-120%). CONCLUSION: The use of corticosteroids at moderate doses increased the risk of serious infection in RA patients. Reduced functionality assessed by the HAQ and comorbidities were other important factors associated with serious infection in this cohort.

Increased Prolonged Sitting in Patients with Rheumatoid Arthritis during the COVID-19 Pandemic: A Within-Subjects, Accelerometer-Based Study.

BACKGROUND: Social distancing measures designed to contain the COVID-19 pandemic can restrict physical activity, a particular concern for high-risk patient groups. We assessed rheumatoid arthritis patients' physical activity and sedentary behavior level, pain, fatigue, and health-related quality of life prior to and during the social distancing measures implemented in Sao Paulo, Brazil. METHODS: Post-menopausal females diagnosed with rheumatoid arthritis were assessed before (from March 2018 to March 2020) and during (from 24 May to 7 July 2020) social distancing measures to contain COVID-19 pandemic, using a within-subjects, repeated-measure design. Physical activity and sedentary behavior were assessed using accelerometry (ActivPAL micro). Pain, fatigue, and health-related quality of life were assessed by questionnaires. RESULTS: Mean age was 60.9 years and BMI was 29.5 Kg/m2. Disease activity ranged from remission to moderate activity. During social distancing, there were reductions in light-intensity activity (13.0% [-0.2 h/day, 95% CI: -0.4 to -0.04; p = 0.016]) and moderate-to-vigorous physical activity (38.8% [-4.5 min/day, 95% CI: -8.1 to -0.9; p = 0.015]), but not in standing time and sedentary time. However, time spent in prolonged bouts of sitting ≥30 min increased by 34% (1.0 h/day, 95% CI: 0.3 to 1.7; p = 0.006) and ≥60 min increased by 85% (1.0 h/day, 95% CI: 0.5 to 1.6). There were no changes in pain, fatigue, and health-related quality of life (all p > 0.050). CONCLUSIONS: Imposed social distancing measures to contain the COVID-19 outbreak were associated with decreased physical activity and increased prolonged sedentary behavior, but did not change clinical symptoms sitting among patients with rheumatoid arthritis.

Decreasing delays in the diagnosis and treatment of rheumatoid arthritis in Brazil: a nationwide multicenter observational study.

BACKGROUND: Management delays imply worse outcomes in rheumatoid arthritis (RA) and, therefore, should be minimized. We evaluated changes in diagnostic and treatment delays regarding RA in the last decades in Brazil. METHODS: Adults fulfilling the ACR/EULAR (2010) criteria for RA were assessed. Delays in diagnosis and treatment, and the frequencies of early management initiation within thresholds (windows of opportunity) of 3, 6, and 12 months from symptoms onset were evaluated. The Mann-Kendall trend test, chi-squared tests with Cramer's V effect sizes and analysis of variance were conducted. RESULTS: We included 1116 patients: 89.4% female, 56.8% white, mean (SD) age 57.1 (11.5) years. A downward trend was found in diagnostic (tau = - 0.677, p < 0.001) and treatment (tau = - 0.695, p < 0.001) delays from 1990 to 2015. The frequency of early management increased throughout the period, with ascending effect sizes across the 3-, 6-, and 12-month windows (V = 0.120, 0.200 and 0.261, respectively). Despite all improvements, even in recent years (2011-2015) the diagnostic and treatment delays still remained unacceptably high [median (IQR): 8 (4-12) and 11 (5-17) months, respectively], with only 17.2% of the patients treated within the shortest, 3-month window. CONCLUSION: The delays in diagnosis and treatment of RA decreased during the last decades in Brazil. Improvements (effect sizes) were greater at eliminating extreme delays (≥ 12 months) than in attaining really short management windows (≤ 3 months). Very early treatment was still an unrealistic goal for most patients with RA.

Extra-articular manifestations of rheumatoid arthritis remain a major challenge: data from a large, multi-centric cohort.

INTRODUCTION: Although Rheumatoid Arthritis (RA) extra-articular manifestations (ExtRA) occurrence has been decreasing over time, they are still a major mortality risk factor for patients. OBJECTIVE: To determine the prevalence of ExtRA in a large cohort, and its association with demographic and clinical variables. METHOD: Cross-sectional and observational study, based on a multi-centric database from a prospective cohort, in which 11 public rheumatology centres enrolled RA patients (1987 ARA or 2010 ACR-EULAR). Data collection began in 08-2015, using a single online electronic medical record. Continuous variables were compared using Mann-Whitney U-test, and Fisher's exact test or chi-square test, as appropriate, were used for categorical variables. The level of significance was set at 5% (p < 0.05). RESULTS: 1115 patients were included: 89% women, age [mean ± SD] 58.2 ± 11.5 years, disease duration 14.5 ± 12.2 years, positive Rheumatoid Factor (RF, n = 1108) in 77%, positive anti-cyclic citrullinated peptide (ACPA, n = 477) in 78%. Regarding ExtRA, 334 occurrences were registered in 261 patients, resulting in an overall prevalence of 23.4% in the cohort. The comparison among ExtRA and Non-ExtRA groups shows significant higher age (p < 0.001), disease duration (p < 0.001), RF high titers (p = 0.018), Clinical Disease Activity index (CDAI) (p < 0.001), Disease Activity Index 28 (DAS 28) (p < 0.001), and Health Assessment Questionnaire (HAQ) (p < 0.001) in ExtRA group. Treatment with Azathioprine (p = 0.002), Etanercept (p = 0.049) Glucocorticoids (GC) ('p = 0.002), and non-steroidal anti-inflammatory drugs (NSAIDs) (p < 0.001) were more frequent in ExtRA group. CONCLUSIONS: ExtRA manifestations still show an expressive occurrence that should not be underestimated. Our findings reinforce that long-term seropositive disease, associated with significant disability and persistent inflammatory activity are the key factors related to ExtRA development.

Do it fast! Early access to specialized care improved long-term outcomes in rheumatoid arthritis: data from the REAL multicenter observational study.

BACKGROUND: Early rheumatoid arthritis (RA) offers an opportunity for better treatment outcomes. In real-life settings, grasping this opportunity might depend on access to specialized care. We evaluated the effects of early versus late assessment by the rheumatologist on the diagnosis, treatment initiation and long-term outcomes of RA under real-life conditions. METHODS: Adults meeting the ACR/EULAR (2010) or ARA (1987) criteria for RA were included. Structured interviews were conducted. The specialized assessment was deemed "early" when the rheumatologist was the first or second physician consulted after symptoms onset, and "late" when performed afterwards. Delays in RA diagnosis and treatment were inquired. Disease activity (DAS28-CRP) and physical function (HAQ-DI) were evaluated. Student's t, Mann-Whitney U, chi-squared and correlation tests, and multiple linear regression were performed. For sensitivity analysis, a propensity score-matched subsample of early- vs. late-assessed participants was derived based on logistic regression. The study received ethical approval; all participants signed informed consent. RESULTS: We included 1057 participants (89.4% female, 56.5% white); mean (SD) age: 56.9 (11.5) years; disease duration: 173.1 (114.5) months. Median (IQR) delays from symptoms onset to both RA diagnosis and initial treatment coincided: 12 (6-36) months, with no significant delay between diagnosis and treatment. Most participants (64.6%) first sought a general practitioner. Notwithstanding, 80.7% had the diagnosis established only by the rheumatologist. Only a minority (28.7%) attained early RA treatment (≤ 6 months of symptoms). Diagnostic and treatment delays were strongly correlated (rho 0.816; p < 0.001). The chances of missing early treatment more than doubled when the assessment by the rheumatologist was belated (OR 2.77; 95% CI: 1.93, 3.97). After long disease duration, late-assessed participants still presented lower chances of remission/low disease activity (OR 0.74; 95% CI: 0.55, 0.99), while the early-assessed ones showed better DAS28-CRP and HAQ-DI scores (difference in means [95% CI]: -0.25 [-0.46, -0.04] and - 0.196 [-0.306, -0.087] respectively). The results in the propensity-score matched subsample confirmed those observed in the original (whole) sample. CONCLUSIONS: Early diagnosis and treatment initiation in patients with RA was critically dependent on early access to the rheumatologist; late specialized assessment was associated with worse long-term clinical outcomes.

Association of Bone Erosions and Osteophytes With Systemic Bone Involvement on High-Resolution Peripheral Quantitative Computed Tomography in Premenopausal Women With Longstanding Rheumatoid Arthritis.

OBJECTIVE: To evaluate premenopausal women with longstanding rheumatoid arthritis (RA) for potential associations between parameters of localized bone involvement and parameters of systemic bone involvement in the affected joints. METHODS: Eighty consecutively evaluated premenopausal women with RA were included in the study, along with 160 healthy female control subjects who were matched to the patients by age and body mass index. Volumetric bone mineral density (vBMD), bone microarchitecture, and finite elements of biomechanical bone strength (bone stiffness and estimated failure load) at the distal radius and distal tibia were analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with RA compared to healthy controls. In addition, in patients with RA, localized bone involvement in the metacarpophalangeal and proximal interphalangeal joints was analyzed by HR-pQCT, to identify bone erosions and osteophytes. RESULTS: Among the 80 premenopausal women with longstanding RA, the mean ± SD age was 39.4 ± 6.7 years and mean ± SD disease duration was 9.8 ± 5.3 years. Trabecular and cortical bone parameters and bone strength at the distal radius and distal tibia were all impaired in patients with RA compared to healthy controls (each P < 0.05). In total, 75% of RA patients had evidence of bone erosions, and 41.3% of RA patients had detectable osteophytes on HR-pQCT. RA patients with bone erosions, as compared to RA patients without bone erosions, had lower cortical vBMD (at the distal radius, mean ± SD 980 ± 72 mg HA/cm3 versus 1,021 ± 47 mg HA/cm3 [P = 0.03]; at the distal tibia, 979 ± 47 mg HA/cm3 versus 1,003 ± 34 mg HA/cm3 [P = 0.04]) and higher cortical bone porosity (at the distal radius, mean ± SD 2.8 ± 2.5% versus 1.8 ± 1.6% [P = 0.04]; at the distal tibia, 3.7 ± 1.6% versus 2.7 ± 1.6% [P = 0.01]). In patients with RA, osteophyte volume at the distal radius was positively correlated with trabecular vBMD (r = 0.392, P = 0.02), trabecular number (r = 0.381, P = 0.03), and trabecular stiffness (r = 0.411, P = 0.02), and negatively correlated with trabecular separation (r = -0.364, P = 0.04), as determined by Pearson's or Spearman's correlation test. CONCLUSION: The findings show that premenopausal women with longstanding RA have systemic bone fragility at peripheral joint sites. Moreover, the presence of bone erosions is mainly associated with cortical bone fragility at the distal radius and tibia, and presence of osteophytes is associated with repair of trabecular bone at the distal radius.

Immunogenicity decay and case incidence six months post Sinovac-CoronaVac vaccine in autoimmune rheumatic diseases patients.

The determination of durability and vaccine-associated protection is essential for booster doses strategies, however data on the stability of SARS-CoV-2 immunity are scarce. Here we assess anti-SARS-CoV-2 immunogenicity decay and incident cases six months after the 2nd dose of Sinovac-CoronaVac inactivated vaccine (D210) in 828 autoimmune rheumatic diseases patients compared with 207 age/sex-balanced control individuals. The primary outcome is the presence of anti-S1/S2 SARS-CoV-2 IgG at 6 months compared to 6 weeks after 2nd vaccine dose for decay evaluation. Secondary outcomes are presence of neutralizing antibodies, percent inhibition by neutralizing, geometric mean titers and cumulative incident cases at 6 months after 2nd dose. Anti-S1/S2 IgG positivity and titers reduce to 23.8% and 38% in patients (p < 0.001) during the six-month follow up and 20% and 51% in controls (p < 0.001), respectively. Neutralizing antibodies positivity and percent inhibition declines 41% and 54% in patients (p < 0.001) and 39.7% and 47% in controls (p < 0.001). Multivariate logistic regression analysis show males (OR = 0.56;95% CI0.40-0.79), prednisone (OR = 0.56; 95% CI0.41-0.76), anti-TNF (OR = 0.66;95% CI0.45-0.96), abatacept (OR = 0.29; 95% CI0.15-0.56) and rituximab (OR = 0.32;95% CI0.11-0.90) associate with a substantial reduction in IgG response at day 210 in patients. Although cellular immunity was not assessed, a decrease of COVID-19 cases (from 27.5 to 8.1/100 person-years; p < 0.001) is observed despite the concomitant emergence and spread of the Delta variant. Altogether we show a reduction in immunity 6-months of Sinovac-CoronaVac 2nd dose, particularly in males and those under immunosuppressives therapies, without a concomitant rise in COVID-19 cases. (CoronavRheum clinicaltrials.gov:NCT04754698).