Resumo: Introdução: O fator antiperinuclear (FAP) tem-se salientado na literatura pela sua especi... more Resumo: Introdução: O fator antiperinuclear (FAP) tem-se salientado na literatura pela sua especificidade na artrite reumatóide (AR). É um auto-anticorpo que reage com proteína presente nos grânulos quérato-hialinos de células da mucosa oral humana. Objetivos: ...
Descrição Do métoDo De coleta De eviDências Reunião consensual contando com a participação de méd... more Descrição Do métoDo De coleta De eviDências Reunião consensual contando com a participação de médicos reumatologistas da Sociedade Brasileira de Reumatologia (SBR). O texto tomou como base o trabalho realizado por representantes da SBR, publicado em 2004 na revista brasileira de reumatologia (Artrite Reumatóide: Diagnóstico e Tratamento), acrescido da experiência de reumatologistas e complementado por revisão bibliográfica.
Treatment of rheumatoid arthritis (RA) has evolved dramatically in the last decade. However, litt... more Treatment of rheumatoid arthritis (RA) has evolved dramatically in the last decade. However, little is known about the way rheumatologists in Latin America treat their patients in clinical practice, outside the scope of clinical trials. The objective of this study was to describe treatment patterns at disease onset in early RA with data from a large, multicenter, multinational inception cohort of Latin American patients. Consecutive patients with early RA (<1 year of disease duration as diagnosed by a rheumatologist) from 46 centers in 14 Latin American countries were enrolled in the study. Clinical data, laboratory assessments, and a detailed registry on type of prescriptions were collected at baseline and at 3, 6, 12, 18, and 24 months of follow-up. Hands and feet x-rays were obtained at baseline and at 12 and 24 months. All data were captured in Arthros 6.1 database. Continuous variables were expressed as means and SDs, and categorical variables were expressed as percentages and 95% confidence intervals (95% CIs). Only therapeutic data at baseline are presented, corresponding to the period between disease onset and second visit (3 months). A total of 1093 patients were included. Eighty-five percent were female, and 76% had a positive rheumatoid factor. Mean age at diagnosis was 46.5 (SD, 14.2) years, and mean disease duration at the first visit was 5.8 (SD, 3.8) months. Between baseline and second visit (3 months), 75% of patients (95% CI, 72%-78%) received disease-modifying antirheumatic drugs. Methotrexate (MTX) alone or in combination was the most frequently used (60.5%), followed by antimalarials (chloroquine or hydroxychloroquine, 32.1%), sulfasalazine (7.1%), and leflunomide (LEF, 4%). In 474 patients (43%), initiation of disease-modifying antirheumatic drugs was within the first month after the first visit. In addition, 290 patients (26%; 95% CI, 23%-29%) received combination therapy as initial treatment. The most frequently used combinations were MTX + chloroquine (45%), MTX + hydroxychloroquine (25%), and MTX + sulfasalazine (16%). Eleven patients (1%; 95% CI, 0.5%-1.8%) received biologics. Sixty-four percent (95% CI, 60%-66%) received corticosteroids. Of those, 80% (95% CI, 77%-84%) received 10 mg of oral prednisone or less. In this cohort of Latin American patients with early RA, most patients received MTX very early in their disease course. Combination therapy was used approximately in 1 of every 4 patients as initial therapy. Biologics were rarely used at this early stage, and low-dose prednisone was commonly used.
To assess the incidence of tuberculosis and to screen for latent tuberculosis infection among Bra... more To assess the incidence of tuberculosis and to screen for latent tuberculosis infection among Brazilians with rheumatoid arthritis using biologics in clinical practice. This cohort study used data from the Brazilian Registry of Biological Therapies in Rheumatic Diseases (Registro Brasileiro de Monitoração de Terapias Biológicas - BiobadaBrasil), from 01/2009 to 05/2013, encompassing 1552 treatments, including 415 with only synthetic disease-modifying anti-rheumatic drugs, 942 synthetic DMARDs combined with anti-tumor necrosis factor (etanercept, infliximab, adalimumab) and 195 synthetic DMARDs combined with other biologics (abatacept, rituximab and tocilizumab). The occurrence of tuberculosis and the drug exposure time were assessed, and screening for tuberculosis was performed. Unpaired t-test and Fisher's two-tailed test; p<0.05. The exposure times were 981 patient-years in the controls, 1744 patient-years in the anti-TNF group (adalimumab=676, infliximab=547 and etanercept...
Treatment survival with biological therapy may be influenced by many factors, and it seems to be ... more Treatment survival with biological therapy may be influenced by many factors, and it seems to be different among various rheumatic diseases and biological agents. The goal of the study was to compare the drug survival and the causes of discontinuation of anti-tumoral necrosis factor (anti-TNF) therapy in ankylosing spondylitis (AS) with rheumatoid arthritis (RA). Study participants were a cohort from the Brazilian Registry of Biological Therapies in Rheumatic Diseases (BIOBADABRASIL) between 2008 and 2012. The observation time was up to 4 years following the introduction of the first treatment. Gender, age, disease duration, disease activity, comorbidities, and concomitant therapies were assessed. A total of 1303 patients were included: 372 had AS and 931 had RA in which 38.7 % (n = 504) used infliximab (IFX), 34.9 % (n = 455) used adalimumab (ADA), and 26.4 % (n = 344) used etanercept (ETA). The anti-TNF drug survival of patients with AS was 63.08 months (confidence interval (CI) 60.24, 65.92) and patients with RA was 47.5 months (CI 45.65, 49.36). It was significant higher in AS (log-rank; p ≤ 0.001). Patients with RA discontinued anti-TNF more than patients with AS when adjusted to gender and corticosteroid. The adjHR (95 % CI) was 1.6 (1.14, 2.31). Female patients who were also corticosteroid users, but not of advanced age, have shown lower survival for both diseases (log-rank, p ≤ 0.001). The discontinuation rate of IFX, but not of ADA or ETA, was significantly higher in RA than in SA; HR (95 % CI) was 2.49 (1.46, 4.24). The main causes of discontinuation were ineffectiveness and adverse event in both diseases. AS patients have better drug survival adjusted to gender, age, and corticosteroid. This results appear to be related to the disease mechanism.
To analyse clinical severity/activity of rheumatoid arthritis (RA) according to smoking status. T... more To analyse clinical severity/activity of rheumatoid arthritis (RA) according to smoking status. The QUEST-RA multinational database reviews patients for Core Data Set measures including 28 swollen and tender joint count, physician global estimate, erythrocyte sedimentation rate (ESR), HAQ-function, pain, and patient global estimate, as well as DAS28, rheumatoid factor (RF), nodules, erosions and number of DMARDs were recorded. Smoking status was assessed by self-report as &amp;amp;#39;never smoked&amp;amp;#39;, &amp;amp;#39;currently smoking&amp;amp;#39; and &amp;amp;#39;former smokers&amp;amp;#39;. Patient groups with different smoking status were compared for demographic and RA measures. Among the 7,307 patients with smoking data available, status as &amp;amp;#39;never smoked,&amp;amp;#39; &amp;amp;#39;current smoker&amp;amp;#39; and &amp;amp;#39;former smoker&amp;amp;#39; were reported by 65%, 15% and 20%. Ever smokers were more likely to be RF-positive (OR 1.32;1.17-1.48, p&amp;amp;lt;0.001). Rheumatoid nodules were more frequent in ever smokers (OR 1.41;1.24-1.59, p&amp;amp;lt;0.001). The percentage of patients with erosive arthritis and extra-articular disease was similar in all smoking categories. Mean DAS28 was 4.4 (SD 1.6) in non-smokers vs. 4.0 (SD 1.6) in those who had ever smoked. However, when adjusted by age, sex, disease duration, and country gross domestic product, only ESR remained significantly different among Core Data Set measures (mean 31.7mm in non-smokers vs. 26.8mm in ever smoked category). RA patients who had ever smoked were more likely to have RF and nodules, but values for other clinical status measures were similar in all smoking categories (never smoked, current smokers and former smokers).
ObjectiveTo investigate whether body mass index (BMI), as a proxy for body fat, influences rheuma... more ObjectiveTo investigate whether body mass index (BMI), as a proxy for body fat, influences rheumatoid arthritis (RA) disease activity in a gender-specific manner.MethodsConsecutive patients with RA were enrolled from 25 countries into the QUEST-RA program between 2005 and 2008. Clinical and demographic data were collected by treating rheumatologists and by patient self-report. Distributions of Disease Activity Scores (DAS28), BMI, age, and disease duration were assessed for each country and for the entire dataset; mean values between genders were compared using Student’s t-tests. An association between BMI and DAS28 was investigated using linear regression, adjusting for age, disease duration and country.ResultsA total of 5,161 RA patients (4,082 women and 1,079 men) were included in the analyses. Overall, women were younger, had longer disease duration, and higher DAS28 scores than men, but BMI was similar between genders. The mean DAS28 scores increased with increasing BMI from normal to overweight and obese, among women, whereas the opposite trend was observed among men. Regression results showed BMI (continuous or categorical) to be associated with DAS28. Compared to the normal BMI range, being obese was associated with a larger difference in mean DAS28 (0.23, 95% CI: 0.11, 0.34) than being overweight (0.12, 95% CI: 0.03, 0.21); being underweight was not associated with disease activity. These associations were more pronounced among women, and were not explained by any single component of the DAS28.ConclusionBMI appears to be associated with RA disease activity in women, but not in men.
Objetivos: O presente estudo teve por objetivo descrever o processo de implementação de um regist... more Objetivos: O presente estudo teve por objetivo descrever o processo de implementação de um registro nacional em um país em desenvolvimento (Brasil) e relatar os principais resultados preliminares do registro BiobadaBrasil. Material e Métodos: Através de um acordo com a PANLAR, o protocolo Biobadaser foi utilizado como modelo para a implementação de um novo registro no nosso país. Durante os dois primeiros anos desse esforço, o protocolo original foi adaptado, traduzido e apresentado a todos os reumatologistas brasileiros. Durante dez meses, dados de 1.037 pacientes (750 tratados com biológicos e 287 controles) de 15 centros foram coletados. Resultados: A maioria dos pacientes tinha artrite reumatoide (AR) (n = 723). Infliximabe foi o agente anti-TNF mais usado, e a exposição total a biológicos foi 2.101 pacientes-ano. A razão mais comum para suspensão da droga foi ineficiência ou perda de efetividade (50%), e 30% dos pacientes interromperam o tratamento devido a eventos adversos. Três casos de tuberculose foram observados no grupo biológico, representando maior incidência do que aquela da população brasileira geral. Infecções foram observadas em 23% dos pacientes do grupo biológico, sendo o trato respiratório superior o local mais comumente afetado. Apenas um caso de hanseníase tuberculoide foi observado. Nenhuma morte nem malignidade atribuível ao efeito dos medicamentos foi observada até fevereiro de 2010. Conclusões: A implementação do registro foi bem sucedida. Embora recente, o registro BiobadaBrasil já forneceu importantes dados.
Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 2010
To develop guidelines for Musculoskeletal Ultrasound (MSKUS) training for rheumatologists in the ... more To develop guidelines for Musculoskeletal Ultrasound (MSKUS) training for rheumatologists in the Americas.
Treatment of rheumatoid arthritis (RA) has evolved dramatically in the last decade. However, litt... more Treatment of rheumatoid arthritis (RA) has evolved dramatically in the last decade. However, little is known about the way rheumatologists in Latin America treat their patients in clinical practice, outside the scope of clinical trials. The objective of this study was to describe treatment patterns at disease onset in early RA with data from a large, multicenter, multinational inception cohort of Latin American patients. Consecutive patients with early RA (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1 year of disease duration as diagnosed by a rheumatologist) from 46 centers in 14 Latin American countries were enrolled in the study. Clinical data, laboratory assessments, and a detailed registry on type of prescriptions were collected at baseline and at 3, 6, 12, 18, and 24 months of follow-up. Hands and feet x-rays were obtained at baseline and at 12 and 24 months. All data were captured in Arthros 6.1 database. Continuous variables were expressed as means and SDs, and categorical variables were expressed as percentages and 95% confidence intervals (95% CIs). Only therapeutic data at baseline are presented, corresponding to the period between disease onset and second visit (3 months). A total of 1093 patients were included. Eighty-five percent were female, and 76% had a positive rheumatoid factor. Mean age at diagnosis was 46.5 (SD, 14.2) years, and mean disease duration at the first visit was 5.8 (SD, 3.8) months. Between baseline and second visit (3 months), 75% of patients (95% CI, 72%-78%) received disease-modifying antirheumatic drugs. Methotrexate (MTX) alone or in combination was the most frequently used (60.5%), followed by antimalarials (chloroquine or hydroxychloroquine, 32.1%), sulfasalazine (7.1%), and leflunomide (LEF, 4%). In 474 patients (43%), initiation of disease-modifying antirheumatic drugs was within the first month after the first visit. In addition, 290 patients (26%; 95% CI, 23%-29%) received combination therapy as initial treatment. The most frequently used combinations were MTX + chloroquine (45%), MTX + hydroxychloroquine (25%), and MTX + sulfasalazine (16%). Eleven patients (1%; 95% CI, 0.5%-1.8%) received biologics. Sixty-four percent (95% CI, 60%-66%) received corticosteroids. Of those, 80% (95% CI, 77%-84%) received 10 mg of oral prednisone or less. In this cohort of Latin American patients with early RA, most patients received MTX very early in their disease course. Combination therapy was used approximately in 1 of every 4 patients as initial therapy. Biologics were rarely used at this early stage, and low-dose prednisone was commonly used.
Both healthy ageing and rheumatoid arthritis (RA) are frequently associated with acquired steroid... more Both healthy ageing and rheumatoid arthritis (RA) are frequently associated with acquired steroid resistance. Here, we investigated the potential involvement of steroid resistance with multidrug resistance (MDR) and explored the impact of pathological ageing on lymphocyte sensitivity to glucocorticoids. Seventy-four RA patients and 26 healthy controls took part in this study. Peripheral blood mononuclear cells were isolated and T-cell sensitivity to glucocorticoids was measured in vitro. The functional activity of P-glycoprotein was analyzed by flow cytometry and ABCB1/MDR-1 gene polymorphisms were assessed in peripheral lymphocytes. Patients and controls had similar sensitivities to glucocorticoids. Only controls presented age-related immunological changes, including reduced T-cell proliferation and relative resistance to corticosterone. Patients had a higher percentage (72%) of lymphocytes actively extruding rhodamine 123 (Rh123 dim ) than controls (60%) in spite of similar P-glycoprotein activity. A higher percentage of Rh123 dim + lymphocytes was observed in patients who were more resistant to dexamethasone in vitro. The distribution of ABCB1 genotypes in RA patients did not differ significantly from that in controls and were not associated to steroid sensitiveness or disease activity. These data suggest that peripheral lymphocytes of arthritic patients are fully responsive to GCs in vitro in spite of displaying higher MDR activity.
Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 2010
To develop guidelines for Musculoskeletal Ultrasound (MSKUS) training for rheumatologists in the ... more To develop guidelines for Musculoskeletal Ultrasound (MSKUS) training for rheumatologists in the Americas.
To compare the diagnostic powers of rheumatoid factor (RF) and anti-cyclic citrullinated peptide ... more To compare the diagnostic powers of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) in a population selected for its high statistical relevance, over a 6-month period, an informed consent to test for anti-CCP was obtained from 1,025 consecutive patients for whom RF was ordered at a University laboratory. Within 1 year, a diagnosis was obtained without informing the physician about the anti-CCP result. Extensive statistical analyses were performed. A total of 768 patients satisfied the inclusion criteria, and 132 were classified as having RA, yielding a pre-test probability of RA of 17%. The sensitivities for anti-CCP and RF were 62 and 64% (P= 0.83), and the specificities were 97 and 90% (P<0.001), respectively. The positive predictive value (PPV) was 79% for anti-CCP and 56% for RF (P<0.001), whereas the negative predictive value was 92% for both. The likelihood ratio (LR) was 17.9 for anti-CCP and 6.2 for RF (P< 0.005). Forty RA patients were diagnosed with RA of less than 2 years length, and the same significant statistic differences between anti-CCP and RF were observed. Placing the results of both tests together, or using different cutoff points, increased the diagnostic utility of the tests. The anti-CCP test has statistically shown significant higher specificity, PPV, and LR for RA than the RF test in a clinically diverse population. If new criteria are to be devised to help diagnose early RA, anti-CCP should be included because it has a greater diagnostic impact than RF.
Resumo: Introdução: O fator antiperinuclear (FAP) tem-se salientado na literatura pela sua especi... more Resumo: Introdução: O fator antiperinuclear (FAP) tem-se salientado na literatura pela sua especificidade na artrite reumatóide (AR). É um auto-anticorpo que reage com proteína presente nos grânulos quérato-hialinos de células da mucosa oral humana. Objetivos: ...
Descrição Do métoDo De coleta De eviDências Reunião consensual contando com a participação de méd... more Descrição Do métoDo De coleta De eviDências Reunião consensual contando com a participação de médicos reumatologistas da Sociedade Brasileira de Reumatologia (SBR). O texto tomou como base o trabalho realizado por representantes da SBR, publicado em 2004 na revista brasileira de reumatologia (Artrite Reumatóide: Diagnóstico e Tratamento), acrescido da experiência de reumatologistas e complementado por revisão bibliográfica.
Treatment of rheumatoid arthritis (RA) has evolved dramatically in the last decade. However, litt... more Treatment of rheumatoid arthritis (RA) has evolved dramatically in the last decade. However, little is known about the way rheumatologists in Latin America treat their patients in clinical practice, outside the scope of clinical trials. The objective of this study was to describe treatment patterns at disease onset in early RA with data from a large, multicenter, multinational inception cohort of Latin American patients. Consecutive patients with early RA (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1 year of disease duration as diagnosed by a rheumatologist) from 46 centers in 14 Latin American countries were enrolled in the study. Clinical data, laboratory assessments, and a detailed registry on type of prescriptions were collected at baseline and at 3, 6, 12, 18, and 24 months of follow-up. Hands and feet x-rays were obtained at baseline and at 12 and 24 months. All data were captured in Arthros 6.1 database. Continuous variables were expressed as means and SDs, and categorical variables were expressed as percentages and 95% confidence intervals (95% CIs). Only therapeutic data at baseline are presented, corresponding to the period between disease onset and second visit (3 months). A total of 1093 patients were included. Eighty-five percent were female, and 76% had a positive rheumatoid factor. Mean age at diagnosis was 46.5 (SD, 14.2) years, and mean disease duration at the first visit was 5.8 (SD, 3.8) months. Between baseline and second visit (3 months), 75% of patients (95% CI, 72%-78%) received disease-modifying antirheumatic drugs. Methotrexate (MTX) alone or in combination was the most frequently used (60.5%), followed by antimalarials (chloroquine or hydroxychloroquine, 32.1%), sulfasalazine (7.1%), and leflunomide (LEF, 4%). In 474 patients (43%), initiation of disease-modifying antirheumatic drugs was within the first month after the first visit. In addition, 290 patients (26%; 95% CI, 23%-29%) received combination therapy as initial treatment. The most frequently used combinations were MTX + chloroquine (45%), MTX + hydroxychloroquine (25%), and MTX + sulfasalazine (16%). Eleven patients (1%; 95% CI, 0.5%-1.8%) received biologics. Sixty-four percent (95% CI, 60%-66%) received corticosteroids. Of those, 80% (95% CI, 77%-84%) received 10 mg of oral prednisone or less. In this cohort of Latin American patients with early RA, most patients received MTX very early in their disease course. Combination therapy was used approximately in 1 of every 4 patients as initial therapy. Biologics were rarely used at this early stage, and low-dose prednisone was commonly used.
To assess the incidence of tuberculosis and to screen for latent tuberculosis infection among Bra... more To assess the incidence of tuberculosis and to screen for latent tuberculosis infection among Brazilians with rheumatoid arthritis using biologics in clinical practice. This cohort study used data from the Brazilian Registry of Biological Therapies in Rheumatic Diseases (Registro Brasileiro de Monitoração de Terapias Biológicas - BiobadaBrasil), from 01/2009 to 05/2013, encompassing 1552 treatments, including 415 with only synthetic disease-modifying anti-rheumatic drugs, 942 synthetic DMARDs combined with anti-tumor necrosis factor (etanercept, infliximab, adalimumab) and 195 synthetic DMARDs combined with other biologics (abatacept, rituximab and tocilizumab). The occurrence of tuberculosis and the drug exposure time were assessed, and screening for tuberculosis was performed. Unpaired t-test and Fisher's two-tailed test; p<0.05. The exposure times were 981 patient-years in the controls, 1744 patient-years in the anti-TNF group (adalimumab=676, infliximab=547 and etanercept...
Treatment survival with biological therapy may be influenced by many factors, and it seems to be ... more Treatment survival with biological therapy may be influenced by many factors, and it seems to be different among various rheumatic diseases and biological agents. The goal of the study was to compare the drug survival and the causes of discontinuation of anti-tumoral necrosis factor (anti-TNF) therapy in ankylosing spondylitis (AS) with rheumatoid arthritis (RA). Study participants were a cohort from the Brazilian Registry of Biological Therapies in Rheumatic Diseases (BIOBADABRASIL) between 2008 and 2012. The observation time was up to 4 years following the introduction of the first treatment. Gender, age, disease duration, disease activity, comorbidities, and concomitant therapies were assessed. A total of 1303 patients were included: 372 had AS and 931 had RA in which 38.7 % (n = 504) used infliximab (IFX), 34.9 % (n = 455) used adalimumab (ADA), and 26.4 % (n = 344) used etanercept (ETA). The anti-TNF drug survival of patients with AS was 63.08 months (confidence interval (CI) 60.24, 65.92) and patients with RA was 47.5 months (CI 45.65, 49.36). It was significant higher in AS (log-rank; p ≤ 0.001). Patients with RA discontinued anti-TNF more than patients with AS when adjusted to gender and corticosteroid. The adjHR (95 % CI) was 1.6 (1.14, 2.31). Female patients who were also corticosteroid users, but not of advanced age, have shown lower survival for both diseases (log-rank, p ≤ 0.001). The discontinuation rate of IFX, but not of ADA or ETA, was significantly higher in RA than in SA; HR (95 % CI) was 2.49 (1.46, 4.24). The main causes of discontinuation were ineffectiveness and adverse event in both diseases. AS patients have better drug survival adjusted to gender, age, and corticosteroid. This results appear to be related to the disease mechanism.
To analyse clinical severity/activity of rheumatoid arthritis (RA) according to smoking status. T... more To analyse clinical severity/activity of rheumatoid arthritis (RA) according to smoking status. The QUEST-RA multinational database reviews patients for Core Data Set measures including 28 swollen and tender joint count, physician global estimate, erythrocyte sedimentation rate (ESR), HAQ-function, pain, and patient global estimate, as well as DAS28, rheumatoid factor (RF), nodules, erosions and number of DMARDs were recorded. Smoking status was assessed by self-report as &amp;amp;#39;never smoked&amp;amp;#39;, &amp;amp;#39;currently smoking&amp;amp;#39; and &amp;amp;#39;former smokers&amp;amp;#39;. Patient groups with different smoking status were compared for demographic and RA measures. Among the 7,307 patients with smoking data available, status as &amp;amp;#39;never smoked,&amp;amp;#39; &amp;amp;#39;current smoker&amp;amp;#39; and &amp;amp;#39;former smoker&amp;amp;#39; were reported by 65%, 15% and 20%. Ever smokers were more likely to be RF-positive (OR 1.32;1.17-1.48, p&amp;amp;lt;0.001). Rheumatoid nodules were more frequent in ever smokers (OR 1.41;1.24-1.59, p&amp;amp;lt;0.001). The percentage of patients with erosive arthritis and extra-articular disease was similar in all smoking categories. Mean DAS28 was 4.4 (SD 1.6) in non-smokers vs. 4.0 (SD 1.6) in those who had ever smoked. However, when adjusted by age, sex, disease duration, and country gross domestic product, only ESR remained significantly different among Core Data Set measures (mean 31.7mm in non-smokers vs. 26.8mm in ever smoked category). RA patients who had ever smoked were more likely to have RF and nodules, but values for other clinical status measures were similar in all smoking categories (never smoked, current smokers and former smokers).
ObjectiveTo investigate whether body mass index (BMI), as a proxy for body fat, influences rheuma... more ObjectiveTo investigate whether body mass index (BMI), as a proxy for body fat, influences rheumatoid arthritis (RA) disease activity in a gender-specific manner.MethodsConsecutive patients with RA were enrolled from 25 countries into the QUEST-RA program between 2005 and 2008. Clinical and demographic data were collected by treating rheumatologists and by patient self-report. Distributions of Disease Activity Scores (DAS28), BMI, age, and disease duration were assessed for each country and for the entire dataset; mean values between genders were compared using Student’s t-tests. An association between BMI and DAS28 was investigated using linear regression, adjusting for age, disease duration and country.ResultsA total of 5,161 RA patients (4,082 women and 1,079 men) were included in the analyses. Overall, women were younger, had longer disease duration, and higher DAS28 scores than men, but BMI was similar between genders. The mean DAS28 scores increased with increasing BMI from normal to overweight and obese, among women, whereas the opposite trend was observed among men. Regression results showed BMI (continuous or categorical) to be associated with DAS28. Compared to the normal BMI range, being obese was associated with a larger difference in mean DAS28 (0.23, 95% CI: 0.11, 0.34) than being overweight (0.12, 95% CI: 0.03, 0.21); being underweight was not associated with disease activity. These associations were more pronounced among women, and were not explained by any single component of the DAS28.ConclusionBMI appears to be associated with RA disease activity in women, but not in men.
Objetivos: O presente estudo teve por objetivo descrever o processo de implementação de um regist... more Objetivos: O presente estudo teve por objetivo descrever o processo de implementação de um registro nacional em um país em desenvolvimento (Brasil) e relatar os principais resultados preliminares do registro BiobadaBrasil. Material e Métodos: Através de um acordo com a PANLAR, o protocolo Biobadaser foi utilizado como modelo para a implementação de um novo registro no nosso país. Durante os dois primeiros anos desse esforço, o protocolo original foi adaptado, traduzido e apresentado a todos os reumatologistas brasileiros. Durante dez meses, dados de 1.037 pacientes (750 tratados com biológicos e 287 controles) de 15 centros foram coletados. Resultados: A maioria dos pacientes tinha artrite reumatoide (AR) (n = 723). Infliximabe foi o agente anti-TNF mais usado, e a exposição total a biológicos foi 2.101 pacientes-ano. A razão mais comum para suspensão da droga foi ineficiência ou perda de efetividade (50%), e 30% dos pacientes interromperam o tratamento devido a eventos adversos. Três casos de tuberculose foram observados no grupo biológico, representando maior incidência do que aquela da população brasileira geral. Infecções foram observadas em 23% dos pacientes do grupo biológico, sendo o trato respiratório superior o local mais comumente afetado. Apenas um caso de hanseníase tuberculoide foi observado. Nenhuma morte nem malignidade atribuível ao efeito dos medicamentos foi observada até fevereiro de 2010. Conclusões: A implementação do registro foi bem sucedida. Embora recente, o registro BiobadaBrasil já forneceu importantes dados.
Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 2010
To develop guidelines for Musculoskeletal Ultrasound (MSKUS) training for rheumatologists in the ... more To develop guidelines for Musculoskeletal Ultrasound (MSKUS) training for rheumatologists in the Americas.
Treatment of rheumatoid arthritis (RA) has evolved dramatically in the last decade. However, litt... more Treatment of rheumatoid arthritis (RA) has evolved dramatically in the last decade. However, little is known about the way rheumatologists in Latin America treat their patients in clinical practice, outside the scope of clinical trials. The objective of this study was to describe treatment patterns at disease onset in early RA with data from a large, multicenter, multinational inception cohort of Latin American patients. Consecutive patients with early RA (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1 year of disease duration as diagnosed by a rheumatologist) from 46 centers in 14 Latin American countries were enrolled in the study. Clinical data, laboratory assessments, and a detailed registry on type of prescriptions were collected at baseline and at 3, 6, 12, 18, and 24 months of follow-up. Hands and feet x-rays were obtained at baseline and at 12 and 24 months. All data were captured in Arthros 6.1 database. Continuous variables were expressed as means and SDs, and categorical variables were expressed as percentages and 95% confidence intervals (95% CIs). Only therapeutic data at baseline are presented, corresponding to the period between disease onset and second visit (3 months). A total of 1093 patients were included. Eighty-five percent were female, and 76% had a positive rheumatoid factor. Mean age at diagnosis was 46.5 (SD, 14.2) years, and mean disease duration at the first visit was 5.8 (SD, 3.8) months. Between baseline and second visit (3 months), 75% of patients (95% CI, 72%-78%) received disease-modifying antirheumatic drugs. Methotrexate (MTX) alone or in combination was the most frequently used (60.5%), followed by antimalarials (chloroquine or hydroxychloroquine, 32.1%), sulfasalazine (7.1%), and leflunomide (LEF, 4%). In 474 patients (43%), initiation of disease-modifying antirheumatic drugs was within the first month after the first visit. In addition, 290 patients (26%; 95% CI, 23%-29%) received combination therapy as initial treatment. The most frequently used combinations were MTX + chloroquine (45%), MTX + hydroxychloroquine (25%), and MTX + sulfasalazine (16%). Eleven patients (1%; 95% CI, 0.5%-1.8%) received biologics. Sixty-four percent (95% CI, 60%-66%) received corticosteroids. Of those, 80% (95% CI, 77%-84%) received 10 mg of oral prednisone or less. In this cohort of Latin American patients with early RA, most patients received MTX very early in their disease course. Combination therapy was used approximately in 1 of every 4 patients as initial therapy. Biologics were rarely used at this early stage, and low-dose prednisone was commonly used.
Both healthy ageing and rheumatoid arthritis (RA) are frequently associated with acquired steroid... more Both healthy ageing and rheumatoid arthritis (RA) are frequently associated with acquired steroid resistance. Here, we investigated the potential involvement of steroid resistance with multidrug resistance (MDR) and explored the impact of pathological ageing on lymphocyte sensitivity to glucocorticoids. Seventy-four RA patients and 26 healthy controls took part in this study. Peripheral blood mononuclear cells were isolated and T-cell sensitivity to glucocorticoids was measured in vitro. The functional activity of P-glycoprotein was analyzed by flow cytometry and ABCB1/MDR-1 gene polymorphisms were assessed in peripheral lymphocytes. Patients and controls had similar sensitivities to glucocorticoids. Only controls presented age-related immunological changes, including reduced T-cell proliferation and relative resistance to corticosterone. Patients had a higher percentage (72%) of lymphocytes actively extruding rhodamine 123 (Rh123 dim ) than controls (60%) in spite of similar P-glycoprotein activity. A higher percentage of Rh123 dim + lymphocytes was observed in patients who were more resistant to dexamethasone in vitro. The distribution of ABCB1 genotypes in RA patients did not differ significantly from that in controls and were not associated to steroid sensitiveness or disease activity. These data suggest that peripheral lymphocytes of arthritic patients are fully responsive to GCs in vitro in spite of displaying higher MDR activity.
Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 2010
To develop guidelines for Musculoskeletal Ultrasound (MSKUS) training for rheumatologists in the ... more To develop guidelines for Musculoskeletal Ultrasound (MSKUS) training for rheumatologists in the Americas.
To compare the diagnostic powers of rheumatoid factor (RF) and anti-cyclic citrullinated peptide ... more To compare the diagnostic powers of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) in a population selected for its high statistical relevance, over a 6-month period, an informed consent to test for anti-CCP was obtained from 1,025 consecutive patients for whom RF was ordered at a University laboratory. Within 1 year, a diagnosis was obtained without informing the physician about the anti-CCP result. Extensive statistical analyses were performed. A total of 768 patients satisfied the inclusion criteria, and 132 were classified as having RA, yielding a pre-test probability of RA of 17%. The sensitivities for anti-CCP and RF were 62 and 64% (P= 0.83), and the specificities were 97 and 90% (P<0.001), respectively. The positive predictive value (PPV) was 79% for anti-CCP and 56% for RF (P<0.001), whereas the negative predictive value was 92% for both. The likelihood ratio (LR) was 17.9 for anti-CCP and 6.2 for RF (P< 0.005). Forty RA patients were diagnosed with RA of less than 2 years length, and the same significant statistic differences between anti-CCP and RF were observed. Placing the results of both tests together, or using different cutoff points, increased the diagnostic utility of the tests. The anti-CCP test has statistically shown significant higher specificity, PPV, and LR for RA than the RF test in a clinically diverse population. If new criteria are to be devised to help diagnose early RA, anti-CCP should be included because it has a greater diagnostic impact than RF.
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