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.

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.

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.

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

Abstract 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. Key messages Abatacept could increase the chance of reaching an ACR70 response by 2.2-fold compared to tocilizumab.

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

Abstract 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.

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

Abstract 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.

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.

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.

Recommendations of the Brazilian Society of Rheumatology for the use of JAK inhibitors in the management of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic and autoimmune systemic inflammatory disease that can cause irreversible joint deformities, with increased morbidity and mortality and a significant impact on the quality of life of the affected individual. The main objective of RA treatment is to achieve sustained clinical remission or low disease activity. However, up to 40% of patients do not respond to available treatments, including bDMARDs. New therapeutic targets for RA are emerging, such as Janus kinases (JAKs). These are essential for intracellular signaling (via JAK-STAT) in response to many cytokines involved in RA immunopathogenesis. JAK inhibitors (JAKi) have established themselves as a highly effective treatment, gaining increasing space in the therapeutic arsenal for the treatment of RA. The current recommendations aim to present a review of the main aspects related to the efficacy and safety of JAKis in RA patients, and to update the recommendations and treatment algorithm proposed by the Brazilian Society of Rheumatology in 2017.

Cardiovascular risk comorbidities in rheumatoid arthritis patients and the use of anti-rheumatic drugs: a cross-sectional real-life study.

BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune systemic inflammatory disease. In addition to joint involvement, RA patients frequently have other comorbidities, such as cardiovascular diseases. Drugs used for RA treatment may increase or decrease the risk of a cardiovascular event. This study aims to analyze cardiovascular risk comorbidities in patients with RA and the correlation with the use of anti-rheumatic drugs. METHODS: Cross-sectional study conducted based on the real-life rheumatoid arthritis study database - REAL, a prospective observational cohort study. Associations between the use of anti-rheumatic drugs and the presence of comorbidities were represented by their prevalence ratio and evaluated using the Chi-square or Fisher's Exact tests. RESULTS: We assessed 1116 patients, 89.4% women, mean age of 55.15 years and predominance of seropositive disease. 63.3% had some cardiovascular comorbidity, predominantly hypertension (49.9%). The use of glucocorticoids was observed in 47.4% of patients and there was a significant tendency of lower use of these drugs in the presence of dyslipidemia (PR: 0.790; p = 0.007). We observed that the presence of cardiovascular comorbidities was associated with higher use of bDMARDs (PR:1.147; p = 0.003). CONCLUSIONS: The presence of cardiovascular risk comorbidities was confirmed to be higher in RA patients. Different treatment strategies using less glucocorticoids in the presence of dyslipidemia and more common use of bDMARDs in patients with cardiovascular comorbidities suggest that rheumatologists are aware of the potential influence of the DMARDs in the risk of cardiovascular event. Reinforcing these results, we highlight the need for a better baseline assessment to guide the choice of anti-rheumatic drugs in RA patients who have comorbidities.

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.

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.

Cardiovascular risk comorbidities in rheumatoid arthritis patients and the use of anti-rheumatic drugs: a cross-sectional real- life study

Abstract Background: Rheumatoid arthritis (RA) is a common autoimmune systemic inflammatory disease. In addition to joint involvement, RA patients frequently have other comorbidities, such as cardiovascular diseases. Drugs used for RA treatment may increase or decrease the risk of a cardiovascular event. This study aims to analyze cardiovascular risk comorbidities in patients with RA and the correlation with the use of anti-rheumatic drugs. Methods: Cross-sectional study conducted based on the real-life rheumatoid arthritis study database - REAL, a prospective observational cohort study. Associations between the use of anti-rheumatic drugs and the presence of comorbidities were represented by their prevalence ratio and evaluated using the Chi-square or Fisher's Exact tests. Results: We assessed 1116 patients, 89.4% women, mean age of 55.15 years and predominance of seropositive disease. 63.3% had some cardiovascular comorbidity, predominantly hypertension (49.9%). The use of glucocorticoids was observed in 47.4% of patients and there was a significant tendency of lower use of these drugs in the presence of dyslipidemia (PR: 0.790; p = 0.007). We observed that the presence of cardiovascular comorbidities was associated with higher use of bDMARDs (PR:1.147; p = 0.003). Conclusions: The presence of cardiovascular risk comorbidities was confirmed to be higher in RA patients. Different treatment strategies using less glucocorticoids in the presence of dyslipidemia and more common use of bDMARDs in patients with cardiovascular comorbidities suggest that rheumatologists are aware of the potential influence of the DMARDs in the risk of cardiovascular event. Reinforcing these results, we highlight the need for a better baseline assessment to guide the choice of anti-rheumatic drugs in RA patients who have comorbidities.

Real - rheumatoid arthritis in real life - study cohort: a sociodemographic profile of rheumatoid arthritis in Brazil.

BACKGROUND: In Brazil, socioeconomic differences in the incidence of rheumatoid arthritis (RA) have been demonstrated, which are important in the formulation of hypotheses regarding the association between environmental factors, lifestyle and the risk of disease development. This study examines how the socioeconomic condition of the patient with RA in Brazil, assessed according to social class, educational level, employment situation and use of caregivers, affects the times between the beginning of symptoms and diagnosis and the beginning of the use of disease-modifying antirheumatic drugs, as well as the presence of erosive disease and functional status. METHODS: This work is part of a multicentric study called REAL - Rheumatoid Arthritis in Real Life in Brazil, which is a prospective observational cohort study. RESULTS: As described in the REAL study, we included a total of 1115 patients. It was noted that patients with an educational classification of up to second grade incomplete presented with erosion percentages above those with a higher grade complete. Patients with caregivers presented a higher percentage of erosion than patients without caregivers. We verified that patients from economic classes above B2 presented fewer occurrences of erosion than those from classes C2, D-E. We also analyzed the average time differences from the beginning of symptoms and diagnosis and the beginning of treatment, according to academic level, erosion and economic classification. Patients with first grade complete showed an HAQ-DI averages higher than those with second grade complete. The patients who had employment showed lower HAQ-DI averages than patients who were not employed. The patients with erosion showed an HAQ-DI value higher than those without erosion. Patients with caregivers showed an HAQ-DI average higher than that of without caregivers. CONCLUSION: This study showed that the therapeutic window of RA is not being reached, and therefore we should have a policy to expand and ensure access to public health for all patients, especially those with lower levels of education and income. TRIAL REGISTRATION: This study was approved by the National Commission of Ethics in Research.

Discordance between the patient's and physician's global assessment in rheumatoid arthritis: Data from the REAL study-Brazil.

BACKGROUND: Discordance between patient's global assessment (PtGA) and physician's global assessment (PhGA) has been described in rheumatoid arthritis (RA). Understanding the reasons for this discrepancy is important in the context of treat-to-target treatment strategy. OBJECTIVE: To assess the determinants of PtGA and PhGA and factors associated with discordance between them. METHODS: The REAL study included RA patients from Brazilian public health centers. Clinical, laboratory and outcomes measures were collected. PtGA and the PhGA were rated on a visual analog scale and analyzed. Three groups were defined: no discordance (difference between PtGA and PhGA within 3 cm), positive discordance (PtGA exceeding PhGA by >3 cm), and negative discordance (PtGA less than PhGA by >3 cm). Multivariate regression analysis was used to identify determinants of PtGA and PhGA and their discordance. RESULTS: 1115 patients (89,4% female, mean age 56.7y and median disease duration of 12.7y) were enrolled. Two factors were associated with PtGA in the final multivariate model: one point increase in the pain scale leads to an increase of 0.62 in PtGA; one point increase in HAQ increases by 9,25 points the PtGA. The factors associated with PhGA were pain scale, number of tender and swollen joints (NTJ and NSJ), positive RF, ESR, HAQ-DI and use of corticosteroids. Discordance between patient and physician was found in 30.52%: positive discordance in 24.6% and negative discordance in 5.92%. An increase of one point in the NSJ was associated with a 12% increase in the chance of negative discordance. The chance of positive discordance increased by 90% and 2% for each unit increased in HAQ-DI and pain scale respectively. Finally, the chance of positive discordance decreased by 3% for each point increased in NTJ and by 15% for each point increased in NSJ. CONCLUSION: In one-third of the assessments, there was disagreement between PtGA and PhGA (a positive discordance was found in 80% of them). Pain and function were determinants for patients to estimate disease activity, while swollen joints was the main factor related to a worse physician's evaluation. These data show how different can be the perspectives of patients and assistants.

Rheumatoid artrhitis treatment in Brazil: data from a large real-life multicenter study.

BACKGROUND: Last decades witnessed great technological advances in rheumatoid arthritis (RA) management, but their implementation in clinical practice might prove difficult. Despite the efficacy demonstrated in controlled trials this information needs to be confirmed by real life data. This study assessed real-life treatment among RA patients. METHODS: REAL study included Brazilian RA patients from eleven centers. Interview and medical records were performed. Continuous variables were compared using Student's t or Mann-Whitney and categorical variables were assessed with chi-square or Fisher's exact tests. RESULTS: 1115 patients were included, women 89.5%. Median age 56.6 years, disease duration 152.5 months; 78.7% were rheumatoid fator positive; 55.2% had erosive disease; DAS28 (disease activity index-28 joints) = 3.5, HAQ (health assessment questionnaire) =0.875. The median duration of symptoms until the start of first DMARD was 12 months. A total of 529 (47.2%) patients used corticosteroids; 1022 (90.8%) were on conventional synthetic (cs) DMARDs and 406 (36.1%) on biological (b) DMARDs. Methotrexate (MTX) was the most frequent csDMARD: 748 (66.5%) patients, followed by leflunomide (LFN), used by 381 (33.9%) of patients. MTX was associated to LFN in 142 (12.6%) patients. Only five (0.4%) patients used triple therapy (MTX + hydroxychloroquine + sulfasalazine) or sulfasalazine in monotherapy. CONCLUSIONS: Despite advances in therapeutic resources, roughly half RA patients failed achieve T2T goals and 55.2% developed erosive disease. The frequent use of corticosteroids and delay in initiating DMARDs were demonstrated. Issues concerning timely access to medical care are crucial for effective management.

Rheumatoid artrhitis treatment in Brazil: data from a large real-life multicenter study

Abstract Background: Last decades witnessed great technological advances in rheumatoid arthritis (RA) management, but their implementation in clinical practice might prove difficult. Despite the efficacy demonstrated in controlled trials this information needs to be confirmed by real life data. This study assessed real-life treatment among RA patients. Methods: REAL study included Brazilian RA patients from eleven centers. Interview and medical records were performed. Continuous variables were compared using Student's t or Mann-Whitney and categorical variables were assessed with chi-square or Fisher's exact tests. Results: 1115 patients were included, women 89.5%. Median age 56.6 years, disease duration 152.5 months; 78.7% were rheumatoid fator positive; 55.2% had erosive disease; DAS28 (disease activity index-28 joints) = 3.5, HAQ (health assessment questionnaire) =0.875. The median duration of symptoms until the start of first DMARD was 12 months. A total of 529 (47.2%) patients used corticosteroids; 1022 (90.8%) were on conventional synthetic (cs) DMARDs and 406 (36.1%) on biological (b) DMARDs. Methotrexate (MTX) was the most frequent csDMARD: 748 (66.5%) patients, followed by leflunomide (LFN), used by 381 (33.9%) of patients. MTX was associated to LFN in 142 (12.6%) patients. Only five (0.4%) patients used triple therapy (MTX + hydroxychloroquine + sulfasalazine) or sulfasalazine in monotherapy. Conclusions: Despite advances in therapeutic resources, roughly half RA patients failed achieve T2T goals and 55.2% developed erosive disease. The frequent use of corticosteroids and delay in initiating DMARDs were demonstrated. Issues concerning timely access to medical care are crucial for effective management.(AU)

Real - rheumatoid arthritis in real life -study cohort: a sociodemographic profile of rheumatoid arthritis in Brazil

Abstract Background: In Brazil, socioeconomic differences in the incidence of rheumatoid arthritis (RA) have been demonstrated, which are important in the formulation of hypotheses regarding the association between environmental factors, lifestyle and the risk of disease development. This study examines how the socioeconomic condition of the patient with RA in Brazil, assessed according to social class, educational level, employment situation and use of caregivers, affects the times between the beginning of symptoms and diagnosis and the beginning of the use of disease-modifying antirheumatic drugs, as well as the presence of erosive disease and functional status. Methods: This work is part of a multicentric study called REAL - Rheumatoid Arthritis in Real Life in Brazil, which is a prospective observational cohort study. Results: As described in the REAL study, we included a total of 1115 patients. It was noted that patients with an educational classification of up to second grade incomplete presented with erosion percentages above those with a higher grade complete. Patients with caregivers presented a higher percentage of erosion than patients without caregivers. We verified that patients from economic classes above B2 presented fewer occurrences of erosion than those from classes C2, D-E. We also analyzed the average time differences from the beginning of symptoms and diagnosis and the beginning of treatment, according to academic level, erosion and economic classification. Patients with first grade complete showed an HAQ-DI averages higher than those with second grade complete. The patients who had employment showed lower HAQ-DI averages than patients who were not employed. The patients with erosion showed an HAQ-DI value higher than those without erosion. Patients with caregivers showed an HAQ-DI average higher than that of without caregivers. Conclusion: This study showed that the therapeutic window of RA is not being reached, and therefore we should have a policy to expand and ensure access to public health for all patients, especially those with lower levels of education and income. Trial registration: This study was approved by the National Commission of Ethics in Research.(AU)

Correction: Causes of synthetic disease-modifying drug discontinuation in rheumatoid arthritis: Data from a large real-life cohort.

[This corrects the article DOI: 10.1371/journal.pone.0213219.].

Changing rate of serious infections in biologic-exposed rheumatoid arthritis patients. Data from South American registries BIOBADABRASIL and BIOBADASAR.

OBJECTIVE: Most reports on serious infections (SI) in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) are from the USA and Western Europe. Data from other regions are largely missing. We report data from South American countries with different backgrounds and health-care systems but similar registries. METHODS: We merged 2010-2016 data from two registries, BIOBADABRASIL (Brazil) and BIOBADASAR (Argentina), which share the same protocol, online platform and data monitoring process. Patients with active RA were included when they began the first bDMARD or a conventional synthetic DMARD (csDMARD, control group). The SI incidence rate (IR) per 1000 patient/years and adjusted IR ratio (aIRR) were estimated for bDMARDs and csDMARDs. RESULTS: Data were analysed for 3717 RA patients with an exposure of 13,380 patient/years. The 2591 patients treated with bDMARDs (64% tumour necrosis factor-α inhibitors (TNFi)) had a follow-up of 9300 years, and the 1126 treated with csDMARDs had an exposure of 4081 patient/years. The SI IR was 30.54 (CI 27.18-34.30) for all bDMARDs and 5.15 (CI 3.36-7.89) for csDMARDs. The aIRR between the two groups was 2.03 ([1.05, 3.9] p = 0.034) for the first 6 months of treatment but subsequently increased to 8.26 ([4.32, 15.76] p < 0.001). The SI IR for bDMARDs decreased over time in both registries, dropping from 36.59 (28.41-47.12) in 2012 to 7.27 (4.79-11.05) in 2016. CONCLUSION: While SI remains a major concern in South American patients with RA treated with bDMARDs, a favourable trend toward a reduction was observed in the last years.Key Points• New comprehensive data on biologic drugs safety from international collaboration in South America.• First proposal for national registries data merging in South America.• Serious infections remain a major concern in RA patients treated with biologics.• A significant reduction of serious infections in RA patients exposed to biologics was observed over a 7 years period.