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

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.

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.

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.

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)

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.].

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

The treatment of rheumatoid arthritis (RA) has evolved rapidly in recent years. Nonetheless, conventional synthetic disease-modifying drugs (csDMARDs) remain the gold standard for RA treatment. The treatment for RA is expensive and this has a negative impact on public health. Given the low cost of csDMARDs compared to those of other treatment strategies, it is important to manage this type of treatment properly. Information on the duration of use of each drug and the reasons for their discontinuation is relevant to medical practitioners as it could improve the information available regarding side effects and their proper management. Moreover, data from clinical practice in the population can provide health care managers with information for resource allocation and optimization of csDMARD use with a consequent cost reduction in the treatment of RA. In this cross-sectional study, we aimed to describe the use of csDMARDs in public health services in Brazil, emphasizing on the duration of use and reasons for discontinuation of each drug. This study is a part of the REAL, a multicenter project that evaluated Brazilian patients with RA from eleven rheumatology services from August to October 2015. Patients were examined clinically, and an analysis of complementary exams and medical records was performed. A total of 1125 patients were included. 98.5% were women with a median age of 55.6 years. 36% and 90.84% patients were using biological disease-modifying drugs (bDMARDs) and csDMARDs, respectively. The duration of use and doses of each medication and the causes of suspension were analyzed. Most of the patients analyzed in this study were using csDMARDs for prolonged periods and methotrexate showed the longest duration of use. Interruption indexes due to ineffectiveness and side effects were analyzed. The knowledge of common adverse effects may alert attending physicians to the proper management of effective and low-cost therapeutic groups.