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

Abstract 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-Whit-ney 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.

Which factors predict discordance between a patient and physician on a gout flare?

OBJECTIVE: To investigate the factors associated with discordance between patient and physician on the presence of a gout flare. METHODS: Patients' self-reports of current gout flares were assessed with the question, 'Are you having a gout flare today?' which was then compared with a concurrent, blinded, physician's assessment. Based on agreement or disagreement with physicians on the presence of a gout flare, flares were divided into concordant and discordant groups, respectively. Within the discordant group, two subgroups-patient-reported flare but the physician disagreed and physician-reported flare but the patient disagreed-were identified. The factors associated with discordance were analysed with multivariable logistic regression analysis. RESULTS: Of 268 gout flares, 81 (30.2%) flares were discordant, with either patient or physician disagreeing on the presence of a flare. Of the discordant flares, in 57 (70.4%) the patient reported a flare but the physician disagreed. In multivariable logistic regression analysis adjusted for demographics, disagreement among patients and physicians on the presence of a gout flare was associated with lower pain scores at rest [odds ratio (OR) for each point increase on 0-10 point pain scale 0.81 (95% Wald CI 0.73, 0.90), P < 0.0001] and less presence of joint swelling [OR 0.24 (95% CI 0.10, 0.61), P = 0.003] or joint warmth [OR 0.39 (95% CI 0.20, 0.75), P = 0.005]. CONCLUSION: Although patients and physicians generally agree about the presence of gout flare, discordance may occur in the setting of low pain scores and in the absence of swollen or warm joints.

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.

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.

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)

2017 recommendations of the Brazilian Society of Rheumatology for the pharmacological treatment of rheumatoid arthritis.

The objective of this document is to provide a comprehensive update of the recommendations of Brazilian Society of Rheumatology on drug treatment of rheumatoid arthritis (RA), based on a systematic literature review and on the opinion of a panel of rheumatologists. Four general principles and eleven recommendations were approved. General principles: RA treatment should (1) preferably consist of a multidisciplinary approach coordinated by a rheumatologist, (2) include counseling on lifestyle habits, strict control of comorbidities, and updates of the vaccination record, (3) be based on decisions shared by the patient and the physician after clarification about the disease and the available therapeutic options; (4) the goal is sustained clinical remission or, when this is not feasible, low disease activity. Recommendations: (1) the first line of treatment should be a csDMARD, started as soon as the diagnosis of RA is established; (2) methotrexate (MTX) is the first-choice csDMARD; (3) the combination of two or more csDMARDs, including MTX, may be used as the first line of treatment; (4) after failure of first-line therapy with MTX, the therapeutic strategies include combining MTX with another csDMARD (leflunomide), with two csDMARDs (hydroxychloroquine and sulfasalazine), or switching MTX for another csDMARD (leflunomide or sulfasalazine) alone; (5) after failure of two schemes with csDMARDs, a bDMARD may be preferably used or, alternatively a tsDMARD, preferably combined, in both cases, with a csDMARD; (6) the different bDMARDs in combination with MTX have similar efficacy, and therefore, the therapeutic choice should take into account the peculiarities of each drug in terms of safety and cost; (7) the combination of a bDMARD and MTX is preferred over the use of a bDMARD alone; (8) in case of failure of an initial treatment scheme with a bDMARD, a scheme with another bDMARD can be used; in cases of failure with a TNFi, a second bDMARD of the same class or with another mechanism of action is effective and safe; (9) tofacitinib can be used to treat RA after failure of bDMARD; (10) corticosteroids, preferably at low doses for the shortest possible time, should be considered during periods of disease activity, and the risk-benefit ratio should also be considered; (11) reducing or spacing out bDMARD doses is possible in patients in sustained remission.

Sarilumab and Nonbiologic Disease-Modifying Antirheumatic Drugs in Patients With Active Rheumatoid Arthritis and Inadequate Response or Intolerance to Tumor Necrosis Factor Inhibitors.

OBJECTIVE: To evaluate the efficacy and safety of sarilumab plus conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in patients with active moderate-to-severe rheumatoid arthritis (RA) who had an inadequate response or intolerance to anti-tumor necrosis factor (anti-TNF) therapy. METHODS: Patients were randomly allocated to receive sarilumab 150 mg, sarilumab 200 mg, or placebo every 2 weeks for 24 weeks with background conventional synthetic DMARDs. The co-primary end points were the proportion of patients achieving a response according to the American College of Rheumatology 20% criteria for improvement (ACR20) at week 24, and change from baseline in the Health Assessment Questionnaire disability index (HAQ DI) at week 12. Each sarilumab dose was evaluated against placebo; differences between the 2 sarilumab doses were not assessed. RESULTS: The baseline characteristics of the treatment groups were similar. The ACR20 response rate at week 24 was significantly higher with sarilumab 150 mg and sarilumab 200 mg every 2 weeks compared with placebo (55.8%, 60.9%, and 33.7%, respectively; P < 0.0001). The mean change from baseline in the HAQ DI score at week 12 was significantly greater for sarilumab (least squares mean change: for 150 mg, -0.46 [P = 0.0007]; for 200 mg, -0.47 [P = 0.0004]) versus placebo (-0.26). Infections were the most frequently reported treatment-emergent adverse events. Serious infections occurred in 1.1%, 0.6%, and 1.1% of patients receiving placebo, sarilumab 150 mg, and sarilumab 200 mg, respectively. Laboratory abnormalities included decreased absolute neutrophil count and increased transaminase levels in both sarilumab groups compared with placebo. In this study, reductions in the absolute neutrophil count were not associated with an increased incidence of infections or serious infections. CONCLUSION: Sarilumab 150 mg and sarilumab 200 mg every 2 weeks plus conventional synthetic DMARDs improved the signs and symptoms of RA and physical function in patients with an inadequate response or intolerance to anti-TNF agents. Safety data were consistent with interleukin-6 receptor blockade and the known safety profile of sarilumab.

Adherence to the 2012 American College of Rheumatology (ACR) Guidelines for Management of Gout: A Survey of Brazilian Rheumatologists.

OBJECTIVE: To describe the current pharmacological approach to gout treatment reported by rheumatologists in Brazil. METHODS: We performed a cross-sectional survey study using an online questionnaire e-mailed to 395 rheumatologists, randomly selected, from among the members of the Brazilian Society of Rheumatology. RESULTS: Three hundred and nine rheumatologists (78.2%) responded to the survey. For acute gout attacks, combination therapy (NSAIDs or steroid + colchicine) was often used, even in monoarticular involvement, and colchicine was commonly started as monotherapy after 36 hours or more from onset of attack. During an acute attack, urate-lowering therapy (ULT) was withdrawn by approximately a third of rheumatologists. Anti-inflammatory prophylaxis (98% colchicine) was initiated when ULT was started in most cases (92.4%), but its duration was varied. Most (70%) respondents considered the target serum uric acid level to be less than 6 mg/dl. Approximately 50% of rheumatologists reported starting allopurinol at doses of 100 mg daily or less and 42% reported the initial dose to be 300 mg daily in patients with normal renal function. ULT was maintained indefinitely in 76% of gout patients with tophi whereas in gout patients without tophi its use was kept indefinitely in 39.6%. CONCLUSION: This is the first study evaluating gout treatment in a representative, random sample of Brazilian rheumatologists describing common treatment practices among these specialists. We identified several gaps in reported gout management, mainly concerning the use of colchicine and ULT and the duration of anti-inflammatory prophylaxis and ULT. Since rheumatologists are considered as opinion leaders in this disease, a program for improving quality of care for gout patients should focus on increasing their knowledge in this common disease.