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.

Impaired repair properties of endothelial colony-forming cells in patients with granulomatosis with polyangiitis.

In patients with ANCA-associated vasculitis, interactions between neutrophils and endothelial cells cause endothelial damage and imbalance. Endothelial colony-forming cells (ECFCs) represent a cellular population of the endothelial lineage with proliferative capacity and vasoreparative properties. This study aimed to evaluate the angiogenic capacity of ECFCs of patients with granulomatosis with polyangiitis (GPA). The ECFCs of 13 patients with PR3-positive GPA and 14 healthy controls were isolated and characterized using fluorescence-activated cell sorting, capillary tube formation measurement, scratching assays and migration assays with and without plasma stimulation. Furthermore, three patients with active disease underwent post-treatment recollection of ECFCs for longitudinal evaluation. The ECFCs from the patients and controls showed similar capillary structure formation. However, the ECFCs from the patients with inactive GPA exhibited early losses of angiogenic capacity. Impairments in the migration capacities of the ECFCs were also observed in patients with GPA and controls (12th h, p = 0.05). Incubation of ECFCs from patients with GPA in remission with plasma from healthy controls significantly decreased migration capacity (p = 0.0001). Longitudinal analysis revealed that treatment significantly lowered ECFC migration rates. This study revealed that ECFCs from the patients with PR3-positive GPA in remission demonstrated early losses of tube formation and reduced migration capacity compared to those of the healthy controls, suggesting impairment of endothelial function.

18F-FDG PET/CT in Late Acquisition Identifies Sites of Active Disease in Treated Takayasu Arteritis.

OBJECTIVE: Few studies have taken advantage of 18F-fluorodeoxyglucose positron emission tomography associated with computed tomography (18F-FDG PET/CT) to personalize patient evaluation and identify sites of more active disease in Takayasu arteritis (TA)-treated patients. This study aimed to evaluate the utility of 18F-FDG PET/CT in late acquisition in identifying sites of active disease in patients under full treatment for TA. METHODS: In this cross-sectional study, patients under full treatment underwent whole-body 18F-FDG PET/CT. Sites of increased 18F-FDG uptake were classified by a score of 3 on the visual scale using the liver uptake as reference. A quantitative analysis was also performed by measuring the maximum standardized uptake value (SUV) of the vascular wall of affected arteries. Disease activity using the National Institutes of Health criteria was also evaluated. RESULTS: Of the 20 patients, there were 18 female and 2 male patients, with a mean age of 43.6 (±11.58) years and a disease duration of 8.3 (±6.25) years. Thirteen participants (65%) were in inflammatory activity according to the criteria proposed by the National Institutes of Health. All patients received immunosuppressive agents, and one of them received immunobiological treatment. The highest SUV value was 6.2 in the aortic arch, and the lowest was 1.0 in the subclavian artery. The mean maximum SUV did not differ between clinically active and inactive patients. In the visual analysis, all participants had at least 1 vascular site with inflammatory activity, with an uptake ≥2 in relation to the liver. The aortic arch was the most frequently involved site. CONCLUSIONS: This study showed that 18F-FDG PET/CT in late acquisition is an effective imaging method to assess TA activity even in fully treated patients.

The effect of foot orthoses on balance, foot function, and mobility in rheumatoid arthritis: A randomized controlled clinical trial.

OBJECTIVES: To compare balance, foot function and mobility in patients with rheumatoid arthritis with and without foot orthoses. DESIGN: Randomized controlled trial. SETTING: Outpatient rheumatology clinic. SUBJECTS: A total of 94 subjects with rheumatoid arthritis were randomized; of these, 81 were included in the analyses (Intervention group: 40; Control group: 41). INTERVENTION: The Intervention Group received custom-made foot orthoses while the Control Group received none intervention. MAIN MEASURE: The "Foot Function Index," the "Berg Balance Scale," and the "Timed-up-and-go Test" were assessed at baseline an after four weeks. The chosen level of significance was P < 0.05. RESULTS: Average (standard deviation) participant age was 56.7 (±10.6) years old and average disease duration (standard deviation) was 11.4 (± 7.2) years. Groups were similar at baseline, except for comorbidity index and race. After four weeks, significant interaction group versus time was observed for Foot Function Index (change: Intervention group: -1.23 ± 1.58; Control group: -0.12 ± 1.16 - P = 0.0012) and for Berg Balance Scale (change: Intervention group: 2 ± 3; Control group: 0 ± 3 - P = 0.0110), but not for the Timed-up-and-go Test (change: Intervention group: -1.34 ± 1.99; Control group: -0.84 ± 2.29 - P = 0.0799). CONCLUSION: Foot orthoses improved foot function and balance in patients with rheumatoid arthritis.

Sustained efficacy of a concise self-management programme for hands in systemic sclerosis: a longitudinal case-control observational study.

OBJECTIVES: In a longitudinal case-control observational study, we evaluated the benefits of a self-management programme for hands developed for patients with SSc. METHODS: Patients with SSc included in the intervention group (IG) received a concise self-management programme with emphasis on hand exercises and were evaluated during 24 weeks regarding hand pain, hand function, range of motion, grip and tip and key pinch strength. Results were compared with a control group (CG) with no intervention using an analysis of variance for repeated measures with variables transformed into ranks (P ≤ 0.05). Effect sizes were calculated using Cohen's test. RESULTS: Of 90 patients who were evaluated, seven were excluded at enrolment and 26 were excluded during the follow-up. Data from 57 subjects (IG 40, CG 17) were used for analysis. Groups were similar at baseline, except for the Scleroderma HAQ and tip and key pinch strength. Outcome improvements were noted only in the IG (P ≤ 0.05, large effect size). In the CG, variables did not change or had even worsened (hand grip strength and finger motion). CONCLUSIONS: This self-management programme based on hand exercises for SSc resulted in pain reduction and hand function, strength and range of motion improvement. It can be a simple and useful intervention, especially when a regular rehabilitation programme is not available.

Incidence of Infectious Adverse Events in Patients With Rheumatoid Arthritis and Spondyloarthritis on Biologic Drugs-Data From the Brazilian Registry for Biologics Monitoring.

BACKGROUND: The safety profile of biologic drugs might present substantial regional differences. Since 2009, the Brazilian Society of Rheumatology has maintained BIOBADABRASIL (Brazilian Registry for Biologic Drugs), a registry for monitoring of biologic therapies in rheumatic diseases. OBJECTIVES: The aim of this study was to verify the incidence rate (IR) of serious infections in rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients on biologic drugs. METHODS: BIOBADABRASIL prospectively included patients with rheumatic diseases who started the first biologic drug or a synthetic disease-modifying antirheumatic drug as a parallel control group. This study focuses on serious infectious adverse events (SIAEs) in RA and SpA patients on biologic drugs compared with controls, from January 2009 to June 2015. Time of exposure was set from initiation of the drug to the date of last administration or censorship. Serious infectious adverse events IR was calculated per 1000 patient/years with 95% confidence interval (CI). RESULTS: A total of 1698 patients (RA, 1121; SpA, 577) were included, 7119 patient/years. Serious infectious adverse events were more common among patients on tumor necrosis factor inhibitors (TNFi's) than controls (adjusted IR ratio, 2.96 [95% CI, 2.01-4.36]; p < 0.001). Subsequent TNFi was associated with a higher SIAEs incidence when compared with first TNFI (adjusted IR ratio, 1.55 [95% CI, 1.15-2.08]; p = 0.004). Serious infectious adverse events were associated with age and corticosteroids intake. Serious infectious adverse events were more frequent in the respiratory tract in all subgroups. CONCLUSIONS: In BIOBADABRASIL, biologic drugs, especially the subsequent TNFi, were associated with a higher risk of serious infections compared with synthetic DMARDs. Corticosteroid intake and age represented risk factors for SIAEs. Constant monitoring is required to follow the safety profile of drugs in the clinical setting of rheumatic conditions in Brazil.

The evaluation of a home-based program for hands in patients with systemic sclerosis.

STUDY DESIGN: This study used a quasi-experimental design where patients were evaluated before and after participation in the self-management program. INTRODUCTION: Hands are commonly affected in systemic sclerosis (SSc). Strategies to maintain or improve hand function are indicated upon diagnosis and throughout the course of the disease. PURPOSE OF THE STUDY: The purpose of this study was to develop and evaluate a home-based program for hands in patients with SSc. METHODS: A home-based self-management program that consisted of concise instructions about SSc and hand exercises was developed and evaluated in a group of patients with SSc during 8 weeks. Primary outcome measures were hand pain (Visual Analogue Scale) and hand function (Cochin Hand Function Scale). Secondary outcome measures were disability (Scleroderma Health Assessment Questionnaire), finger motion (delta finger-to-palm), grip strength, tip and key pinch strength, Raynaud phenomenon and digital ulcers impact, quality of life (Short Form Health Survey). For comparisons between different times analysis of variance for repeated measures was used. To calculate the effect size (ES), the Cohen's test was performed. To evaluate skin moisturizing and warming habits before and after intervention, the McNemar test was used. Statistical significance was set at P ≤ .05. RESULTS: Twenty-two SSc patients (19 women: 3 men; 16 limited scleroderma: 6 diffuse scleroderma) completed the program. Significant improvements were noted for hand pain (3.97 vs 2.21, ES: 0.69), Cochin Hand Function Scale (19.24 vs 12.48, ES: 0.48), Scleroderma Health Assessment Questionnaire (0.95 vs 0.48, ES: 1.01), delta finger-to-palm (92.86 vs 106.33, ES: 0.40), grip strength (14.43 vs 19, ES: 0.58), tip pinch strength (2.49 vs 4.18, ES: 1.15), key pinch strength (4.01 vs 5.22, ES: 0.76), Raynaud phenomenon impact (0.94 vs 0.47, ES: 0.75), Short Form Health Survey-role physical (47.38 vs 60.14, ES: 0.61), physical functioning (34.62 vs 61.9, ES: 0.18), social functioning (60.71 vs 75.6, ES: 0.64), bodily pain (50.55 vs 63.38, ES: 0.58), vitality (45.95 vs 62, ES: 2.22), mental health (56.62 vs 72.38, ES: 0.84) moisturizing, and cold avoidance habits. Patients considered the program easy to follow with no adverse effects related to exercises. DISCUSSION: We developed a home based hand care program to be offered to SSc patients. Improvements in hand function, strength, disability, motion, and overall quality of life were independent of age, income, education level, disease duration, and skin score. Our findings support those of other studies that reported the benefits of hand exercises in SSc. Some study limitations include the lack of a control group, the small number of subjects and the short-time follow up. CONCLUSIONS: This home-based program for patients with SSc improved hand pain, function, mobility, and strength at the end of 8 weeks. Patient adherence and sustained efficacy is still to be determined.

Assessment of fatigue in a large series of 1492 Brazilian patients with Spondyloarthritis.

BACKGROUND: The aim of the present study was to analyze the score of fatigue in a large cohort of Brazilian patients with SpA, comparing different disease patterns and its association with demographic and disease-specific variables. METHODS: A common protocol of investigation was prospectively applied to 1492 Brazilian patients classified as SpA according to the European Spondyloarthropathies Study Group (ESSG) criteria, attended at 29 reference centers. Clinical and demographic variables were recorded. Fatigue was evaluated using the first item of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questionnaire. RESULTS: The mean BASDAI fatigue score was 4.20 ± 2.99. There was no significant difference in the fatigue score between the different SpA. Fatigue was higher in female patients (p < 0.001), with mixed (axial + peripheral) involvement (p < 0.001) and in those who did not practice exercises (p < 0.001). Higher scores of fatigue were significantly associated with inflammatory low back pain (p = 0.013), alternating buttock pain (p = 0.001), cervical pain (p = 0.001), and hip involvement (p = 0.005). Fatigue presented a moderate positive statistical correlation with Bath Ankylosing Spondylitis Functional Index (BASFI) (0.469; p < 0.001) and Ankylosing Spondylitis Quality of Life (0.462; p < 0.001). CONCLUSION: In this large series of Brazilian SpA patients, higher fatigue scores were associated with female gender, sedentary, worse functionality, and quality of life.

The effect of foot orthoses on balance, foot pain and disability in elderly women with osteoporosis: a randomized clinical trial.

OBJECTIVE: To evaluate the effect of insoles with medial arch support and metatarsal pad on balance, foot pain and disability in elderly women with osteoporosis. METHODS: This was a randomized controlled clinical trial. Ninety-four elderly women (>60 years) with osteoporosis in treatment in the outpatient clinic of the Rheumatology Division of UNICAMP were randomly assigned to an intervention group (IG) with foot orthoses or to a control group (CG) without orthoses. The Berg Balance Scale (BBS), the Timed Up and Go test (TUG), the Manchester Foot Pain and Disability Index (MFPDI) and a numeric pain scale (NPS) were assessed at baseline and after 4 weeks. The chi-squared test, Fisher's exact test and Mann-Whitney test were applied to compare baseline values between the two groups. Repeated measures of analysis of variance followed by Tukey's test for multiple comparisons and the contrast profile test were used to compare the longitudinal measures. For numeric variable relationship analysis, the Spearman correlation coefficient was used. RESULTS: The groups were similar at baseline. Only subjects from the IG displayed improvements in balance (both BBS and TUG), foot pain (NPS) and disability (MFPDI) (P < 0.001). Minor adverse effects were noted. CONCLUSION: Foot orthoses were effective for improving balance and for reducing pain and disability in elderly women. Orthoses can be used as an adjuvant strategy to improve balance and to prevent falls in the elderly.

Schistosoma mansoni infection: an immune complex disease presenting with polyarthritis.

Schistosomiasis or bilharzia is a parasitic disease found in tropical countries. Most infections are subclinical but may progress to chronic form characterized most frequently by the presence of liver involvement and portal hypertension. We report a patient that presented chronic polyarthritis with positive rheumatoid factor. During investigation, increased liver enzymes, negative hepatitis serologies and signs of portal hypertension on an ultrasound examination raised suspicion of S. mansoni infection. We will discuss pathophysiology and clinical manifestations of S. mansoni infection with special attention to articular involvement.

Compared efficacy of rituximab, abatacept, and tocilizumab in patients with rheumatoid arthritis refractory to methotrexate or TNF inhibitors agents: a systematic review and network meta-analysis.

BACKGROUND: Our aim was to compare the efficacy of rituximab, tocilizumab, and abatacept in individuals with rheumatoid arthritis (RA) refractory to treatments with MTX or TNFi agents. METHODS: We searched 6 databases until January 2023 for phase 2-4 RCTs evaluating patients with RA refractory to MTX or TNFi therapy treated with rituximab, abatacept, and tocilizumab (intervention arm) compared to controls. Study data were independently assessed by two investigators. The primary outcome was considered as achieving ACR70 response. RESULTS: The meta-analysis included 19 RCTs, with 7,835 patients and a mean study duration of 1.2 years. Hazard ratios for achieving an ACR70 response at six months were not different among the bDMARDs, however, we found high heterogeneity. Three factors showing a critical imbalance among the bDMARD classes were identified: baseline HAQ score, study duration, and frequency of TNFi treatment in control arm. Multivariate meta-regression adjusted to these three factors were conducted for the relative risk (RR) for ACR70. Thus, heterogeneity was attenuated (I2 = 24%) and the explanatory power of the model increased (R2 = 85%). In this model, rituximab did not modify the chance of achieving an ACR70 response compared to abatacept (RR = 1.773, 95%CI 0.113-10.21, p = 0.765). In contrast, abatacept was associated with RR = 2.217 (95%CI 1.554-3.161, p < 0.001) for ACR70 compared to tocilizumab. CONCLUSION: We found high heterogeneity among studies comparing rituximab, abatacept, and tocilizumab. On multivariate metaregressions, if the conditions of the RCTs were similar, we estimate that abatacept could increase the chance of reaching an ACR70 response by 2.2-fold compared to tocilizumab.

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.

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.

Behçet's disease in Brazilian patients: demographic and clinical features.

The aim of this study was to determine the demographic and clinical characteristics in patients diagnosed with Behçet's disease (BD) in Brazil. We performed a retrospective review of all the patients' records with BD diagnosed from 1988 to 2010 in the Rheumatology Department at the State University of Campinas (UNICAMP). All patients had to fulfill the International Study Group for Behçet's disease diagnostic criteria. Eighty-seven patients were included in the study. The female/male ratio was 1.18:1, and the mean age at the onset of the disease onset was 28.03 ± 7.57 years. Oral aphthosis was the most frequent manifestation (100%). Genital aphthosis was also frequent (77%), followed by pseudofolliculitis (47.67%). Ocular symptoms were present in 80% and neurological manifestations in 31.03% of the patients. Arthralgia was reported in 31.03% and arthritis in 13.79% of the cases. Vascular involvement was seen in 13.95% of the patients. Only 1.14% had gastrointestinal involvement. This series, from a South American country, showed a similar general pattern of the BD to those found in different endemic areas in the world, with a high frequency of ocular and neurological manifestations.

The Structural Index Score and its relation to foot function, disability and physical performance tests in rheumatoid arthritis (RA) - A cross-sectional study.

OBJECTIVES: To evaluate the Structural Index Score (SIS) - a clinical foot deformity assessment index developed for RA, and to compare its results with foot function, disability and physical performance tests. METHODS: In this cross-sectional study, 104 patients with foot pain were evaluated according to SIS score, subscales (Forefoot SIS and Rearfoot SIS) and items. Results were compared with the Foot Function Index (FFI), the Health Assessment Questionnaire Disability Index (using lower limbs items: LL-HAQ), and physical performance tests: Berg Balance Scale (BBS), the Timed Up and Go test (TUG) and the 5-Time Sit down-to-Stand up Test (SST5). RESULTS: There was a weak correlation of SIS score with FFI and LL-HAQ. Rearfoot SIS was correlated with FFI, LL-HAQ and worse performance in BBS, TUG and SST5. Regarding Rearfoot SIS items, the ankle ROM was correlated to all studied outcomes, the calcaneus varus/valgus was correlated with FFI (total, pain and disability subscales) and the planus/cavus deformity with FFI-pain, HAQ-DI and LL-HAQ. Forefoot SIS did not correlate with any outcome measures. In relation to Forefoot SIS items, hallux valgus was associated with foot function (FFI-total, pain and disability subscales), the MTPs joints subluxation was correlated with FFI-disability subscale, and the 5th MTP exostosis was associated with FFI-pain. CONCLUSION: SIS score was correlated to impaired foot function (FFI) and disability (LL-HAQ). Rearfoot SIS was correlated to worse performance on FFI, LL-HAQ, BBS, TUG and SST5. SIS score index can be a useful tool to evaluate the rheumatoid foot deformities, but a better graduation of foot deformities should add sensitivity to this method.

Comparison of rheumatoid arthritis composite disease activity indices and residual activity in a Brazilian multicenter study- REAL study.

INTRODUCTION: Rheumatoid arthritis (RA) composite disease activity indices have become handy tools in daily clinical practice and crucial in defining remission or low disease activity, the main target of the RA treatment. However, there is no definition of the best index to assess disease activity in clinical practice. OBJECTIVES: To compare the residual activity among the indices with the ACR/EULAR remission criteria (Boolean method) to identify the most feasible for assessing remission in daily practice, also considering correlation and concordance, sensibility, and specificity. PATIENTS AND METHODS: We selected 1116 patients with established RA from the real-life rheumatoid arthritis study database-REAL. The composite disease activity indices-DAS28-ESR, DAS28-CRP, SDAI, and CDAI-and their components were compared to the Boolean method to identify residual activity using binomial regression. The indices were analyzed for correlation and agreement using the Spearman index and weighted kappa. The chi-square test evaluated sensibility and specificity for remission based on the Boolean method. RESULTS: DAS28-CRP overestimated remission and confirmed higher residual activity than SDAI and CDAI. The indices showed good correlation and agreement, with a better relationship between SDAI and CDAI (k:0,88). CDAI and SDAI showed higher sensitivity and specificity for remission based on the Boolean method. CDAI was performed in 99% of patients, while DAS28 and SDAI were completed in approximately 85%. CONCLUSIONS: Although all composite indices of activity can be used in clinical practice and showed good agreement, CDAI and SDAI have better performance in evaluating remission based on the Boolean method, showing less residual activity and higher sensibility and specificity. In addition, CDAI seems to be more feasible for disease activity evaluation in daily clinical practice, especially in developing countries.

Investigation on Brazilian clinical practices in rheumatoid arthritis: the Brazilian rheumatoid arthritis clinical practices investigation--BRACTICE.

UNLABELLED: Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease causing significant social, medical, and economic impact. Several therapeutic regimens are available within the medical arsenal. The rational and reasoned use of various medications approved for their treatment is imperative. This study aimed to evaluate how Brazilian rheumatologists use the drugs available to combat the disease.For this, 128 Brazilian rheumatologists from public and private health services responded to an 18-item questionnaire, sent over the Internet, about different situations of drug treatment of RA. The answers helped to confirm the trends among Brazilian rheumatologists in the drug treatment of RA.The study results have shown that most Brazilian rheumatologists follow the guidelines and consensus established by the Brazilian Society of Rheumatology for the treatment of RA. A small proportion, however, start the biologic therapy in early stages of the disease, including the very early stage, as the first treatment option. Most experts use corticosteroids in low doses early in the treatment. CONCLUSIONS: This study confirms that the majority but not all Brazilian rheumatologists follow, in their daily practice, established guidelines and consensus for the treatment of RA. However, it also shows that some few rheumatologists start with anti-tumor necrosis factor therapy in very early arthritis independently of disease severity or prognostic factors.

Effects of Anti-TNF alpha Therapy on Blood Pressure in Resistant Hypertensive Subjects: A Randomized, Double-Blind, Placebo-Controlled Pilot Study. / Efeitos da Terapia com Anti-TNF alfa na Pressão Arterial em Pacientes com Hipertensão Resistente: Um Estudo Piloto Randomizado, Duplo-Cego e Controlado por Placebo.

BACKGROUND: The cytokine tumor necrosis factor-alpha (TNF-α) is elevated in resistant hypertension (RH), but the effects of a TNF-α inhibitor in this population is unknown. OBJECTIVE: The aim of this trial was to evaluate whether a single dose of infliximab controlled by placebo acutely reduces blood pressure (BP) in RH subjects. METHODS: A double-blind, placebo-controlled, crossover trial was conducted, and randomized RH subjects received either infliximab or placebo. The primary endpoint was the change in mean BP levels relative to the baseline immediately after the infusion obtained by continuously beat-to-beat non-invasive hemodynamic assessment. Secondary endpoints included changes in office, ambulatory and central BP measurements; endothelial function; and inflammatory biomarkers after 7 days. The level of significance accepted was alpha=0.05. RESULTS: Ten RH subjects were enrolled. The primary endpoint analysis showed an acute decrease in mean BP values (mean of differences ± standard deviation = -6.3 ± 7.2 mmHg, p=0.02) from baseline, after the application of infliximab compared with placebo. Diastolic BP levels (-4.9 ± 5.5 mmHg, p=0.02), but not systolic BP levels (-9.4 ± 19.7 mmHg, p=0.16), lowered after infliximab infusion. No further significant differences were identified in either the other hemodynamic parameters or in secondary endpoints, except for TNF-α levels, which increased continuously after infliximab infusion. No adverse events were reported during the protocol. CONCLUSIONS: A single-dose of infliximab decreased the mean and diastolic BP levels immediately after its infusion, when compared to the placebo in RH. The anti-TNF-α therapy was found to be safe and well-tolerated. The results of this proof-of-concept are hypothesis-generating and need to be further investigated. (Arq Bras Cardiol. 2021; 116(3):443-451).

FUNDAMENTO: A citocina fator de necrose tumoral alfa (TNF-α) é elevada na hipertensão resistente (HAR), mas os efeitos dos inibidores de TNF-α nessa população ainda são desconhecidos. OBJETIVOS: O objetivo deste estudo foi avaliar se uma única dose de infliximabe controlada por placebo reduz a pressão arterial (PA) de forma aguda em pacientes com HAR. MÉTODOS: Realizamos um estudo cruzado, randomizado, duplo-cego e controlado por placebo em que pacientes com HAR receberam infliximabe ou placebo. O desfecho primário foi a alteração dos níveis de PA média em relação ao basal imediatamente após a infusão, obtida por avaliação hemodinâmica não invasiva contínua, batimento a batimento. Os desfechos secundários incluíram alterações em medidas de PA central, ambulatorial e em consultório, na função endotelial, e nos biomarcadores inflamatórios após 7 dias. O nível de significância aceito foi alfa=0,05. RESULTADOS: Foram incluídos dez portadores de HAR. O resultado do desfecho primário demonstrou uma redução aguda dos níveis de PA média (média das diferenças ± desvio padrão = -6,3 ± 7,2 mmHg, p=0,02) em relação ao basal, após o uso de infliximabe, em comparação com o placebo. Os níveis de PA diastólica (-4,9 ± 5,5 mmHg, p=0,02), mas não os níveis de PA sistólica (-9,4 ± 19,7 mmHg, p=0,16), reduziram após a infusão de infliximabe. Não foram identificadas diferenças significativas nos demais parâmetros hemodinâmicos, nem nos resultados dos desfechos secundários, com exceção dos níveis de TNF-α, que aumentaram continuamente após o uso de infliximabe. Não foram relatados eventos adversos durante o protocolo. CONCLUSÕES: Uma dose única de infliximabe reduziu os níveis de PA média e diastólica imediatamente após sua infusão, em comparação com placebo em HAR. A terapia com anti-TNF-α foi considerada segura e bem tolerada. Os resultados desse estudo prova de conceito são geradores de hipótese e precisam ser investigados em maior detalhe. (Arq Bras Cardiol. 2021; 116(3):443-451).

Real-life data of survival and reasons for discontinuation of biological disease-modifying drugs 'in' rheumatoid arthritis.

Background Rheumatoid arthritis is a chronic, autoimmune disease in which treatment has evolved with a variety of therapeutic classes. Biological disease-modifying antirheumatic drugs have improved therapy; however, the continued long-term use of these drugs with sustained safety and efficacy remains a challenge. ObjectiveThe objective of this study was to analyze time of use and reasons for discontinuation of biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.SettingIt is as part of REAL (Rheumatoid Arthritis in Real Life), a multicenter project that evaluated Brazilian patients with rheumatoid arthritis in a real-life setting. Eleven referral centers for the treatment in the public network participated in the study.MethodsWe conducted a cross-sectional analysis of data collected in the REAL study from August to October 2015 study. The patients were submitted to clinical evaluation and analysis of medical records.Results1125 patients were included (89.5% women; median age: 56.6 years; and disease time: 12.8 years). A total of 406 (36.09%) participants were on a biological disease-modifying antirheumatic drugs. Infliximab was the drug with the longest time of use (12 years). Most (64.4%) drug suspension episodes were due to inefficacy. Adalimumab and certolizumab had a greater number of suspensions due to primary inefficacy, while discontinuations for abatacept were due more to secondary inefficacy. Infliximab had fewer suspensions due to primary inefficacy and golimumab had fewer episodes of secondary inefficacy. Regarding side effects, infliximab was suspended a greater number of times because of clinical and laboratory side effects. Abatacept and adalimumab had fewer suspensions due to clinical side effects, and certolizumab, rituximab and tocilizumab had fewer laboratory adverse effects. Conclusion Among the biological disease-modifying antirheumatic drugs being used for long periods, infliximab had greater time of use. Most drug suspensions (64%) were due to primary or secondary inefficacy. Number of discontinuations due to clinical and laboratory adverse effects for each drug was analyzed, and these data should be confirmed by other real-life studies. Knowledge of what is happening in real life is essential to health professionals, who need to be aware of the most common adverse effects and to health managers, who aim for greater cost-effectiveness in the choice of medications.