The effect of antimalarials on the safety and persistence of treatment with biologic agents or Janus kinase inhibitors in rheumatoid arthritis.

OBJECTIVES: To test the association of use of antimalarials with the overall safety of treatment in RA patients receiving one or multiple courses of biologic (b)DMARDs or a Janus kinase inhibitor (JAKi). METHODS: BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their first bDMARD or JAKi. The present analysis includes RA patients recruited from January 2009 to October 2019, followed up over one or multiple (up to six) courses of treatment (latest date, 19 November 2019). The primary outcome was the incidence of serious adverse events (SAEs). Total and system-specific adverse events (AEs) and treatment interruption served as secondary outcomes. Negative binomial regression with generalized estimating equations (to estimate multivariate incidence rate ratios, mIRR) and frailty Cox proportional hazards models were used for statistical analyses. RESULTS: The number of patients enrolled was 1316 (2335 treatment courses, 6711 patient-years [PY]; 1254.5 PY on antimalarials). The overall incidence of SAEs was 9.2/100 PY. Antimalarials were associated with reduced risk of SAEs (mIRR: 0.49; 95% CI: 0.36, 0.68; P < 0.001), total AEs (0.68; 95% CI: 0.56, 0.81; P < 0.001), serious infections (0.53; 95% CI: 0.34, 0.84; P = 0.007) and total hepatic AEs (0.21; 95% CI: 0.05, 0.85; P = 0.028). Antimalarials were also related to better survival of treatment course (P = 0.003). There was no significant increase in the risk of cardiovascular AEs. CONCLUSION: Among RA patients on treatment with bDMARDs or JAKi, concomitant use of antimalarials was associated with reduced the incidence of serious and total AEs and with longer treatment course survival.

Rheumatoid arthritis and nutritional profile: A study in Brazilian females.

BACKGROUND: Patients with rheumatoid arthritis (RA) may have nutritional impairment. In RA, muscle loss is associated with an increase in fat tissue, and the patients may not have body mass index (BMI) alterations. AIM: To study the nutritional status in a sample of patients with RA in Brazil through mini nutritional assessment (MNA) and electric bioimpedance and its relationship to BMI, functionality, disease activity, and treatment. METHODS: Seventy-one RA females were included. Chart review was used to obtain epidemiological, clinical, and treatment data. Patients answered the MNA and were submitted to electrical bioimpedance and anthropometric measurements. Disease activity was assessed through simple disease activity index (SDAI), clinical disease activity index (CDAI), and function, through health assessment questionnaire (HAQ). RESULTS: According to MNA, 23 (32.4%) patients were at risk for malnutrition and 1 (1.4%) was malnourished. MNA were associated with disease activity and function impairment (SDAI P = .02; CDAI P = .02, and HAQ P = .002) but not with used medications. According to BMI, 76% were overweight or obese. An increased percentage of body fat was found in 98.7% and a lower percentage of lean mass in 95.7%. Disease activity and function were not associated with the percentage of body fat of any used medications, with a lower percentage of body fat in those using abatacept (P = .01). CONCLUSION: Almost one-third of patients had nutritional impairment according to MNA which was associated with disease activity and loss of function. Almost the whole sample had an increased percentage of fat mass and a diminished percentage of muscle mass that could not be linked with disease activity, function or used medications.

O índice de massa corporal tem algum papel na atividade inflamatória na artrite reumatoide / Does the body mass index have any role in inflammatory activity in rheumatoid arthritis?

Artrite reumatoide é doença reumática autoimune e crônica. Acredita-se que a obesidade pode intervir nos seus parâmetros inflamatórios. O objetivo deste estudo foi verificar se existe correlação entre atividade inflamatória dela e o índice de massa corporal (IMC).É estudo transversal retrospectivo nos quais foram obtidos dados de biometria (peso e altura) para cálculo do IMC e de atividade inflamatória. Estudaram-se 676 pacientes (87,5% mulheres com mediana de idade de 59,6 anos). Nesta população, 1,3% estava abaixo do peso normal; 28,1% dentro do peso normal; 35,3% sobrepeso; 31% obesidade grau I e 4,1% obesidade grau 2. Encontrou-se fraca correlação entre o DAS 28-PCR com o IMC. Correlações com os demais parâmetros de inflamação foram não significantes. Em conclusão existe alta proporção de pacientes com artrite reumatoide acima do peso normal e fraca correlação entre IMC e DAS28-PCR

Rheumatoid arthritis is an autoimmune and chronic rheumatic disease. It is believed that obesity can intervene in its inflammatory parameters. The objective of this study was to verify if there is a correlation between her inflammatory activity and the body mass index (BMI). It is a retrospective cross-sectional study in which biometric data (weight and height) were obtained to calculate BMI and inflammatory activity. We studied 676 patients (87.5% women with a median age of 59.6 years). In this population, 1.3% were underweight; 28.1% within normal weight; 35.3% overweight; 31% grade I obesity and 4.1% grade 2 obesity. We found a weak correlation between DAS 28-CRP and BMI. Correlations with the other inflammation parameters were not significant. In conclusion, there is a high proportion of patients with rheumatoid arthritis above normal weight and a weak correlation between BMI and DAS28-CRP

Safety of the Methotrexate-leflunomide Combination in Rheumatoid Arthritis: Results of a Multicentric, Registry-based, Cohort Study (BiobadaBrasil).

OBJECTIVE: To evaluate the safety of the methotrexate (MTX)-leflunomide (LEF) combination in rheumatoid arthritis (RA), comparing it with other therapeutic schemes involving conventional synthetic (cs-) and biologic (b-) disease-modifying antirheumatic drugs (DMARDs) or Janus kinase inhibitors (JAKi). METHODS: Patients with RA starting a treatment course with a csDMARD (without previous use of bDMARD or JAKi) or their first bDMARD/JAKi were followed up in a registry-based, multicentric cohort study in Brazil (BiobadaBrasil). The primary outcome was the incidence of serious adverse events (SAEs); secondary outcomes included serious infections. Multivariate Cox proportional hazards models and propensity score matching analysis (PSMA) were used for statistical comparisons. RESULTS: In total, 1671 patients (5349 patient-years [PY]) were enrolled; 452 patients (1537 PY) received MTX + LEF. The overall incidence of SAEs was 5.6 per 100 PY. The hazard of SAEs for MTX + LEF was not higher than for MTX or LEF (adjusted HR [aHR] 1.00, 95% CI 0.76-1.31, P = 0.98). MTX + LEF presented a lower hazard of SAEs (aHR 0.56, 95% CI 0.36-0.88, P = 0.01) and infectious SAEs (aHR 0.48, 95% CI 0.25-0.94, P = 0.03) than bDMARDs/JAKi with MTX or LEF. MTX + LEF presented lower hazard of SAEs than MTX + sulfasalazine (SSZ; aHR 0.33, 95% CI 0.16-0.65, P = 0.002). Analysis using PSMA confirmed the results obtained with traditional multivariate Cox analysis. CONCLUSION: In our study, MTX + LEF presented a relatively good overall safety profile in comparison to MTX + SSZ and schemes involving advanced therapies in RA.

Perfil das manifestações musculoesqueléticas em esclerose sistêmica e associação com fator reumatoide / Profile of musculoskeletal manifestations in systemic sclerosis and association with rheumatoid factor

A esclerose sistêmica (ES) é doença sistêmica crônica e autoimune. Estima-se que dor musculoesquelética esteja presente entre 40-80% dos pacientes, sobretudo naqueles com doença difusa precoce. O objetivo deste trabalho foi estudar a prevalência de manifestações musculoesqueléticas em ES, verificar se sua presença altera o perfil clínico, qual a prevalência de fator reumatoide na ES e sua associação com manifestações musculoesqueléticas. É estudo retrospectivo envolvendo 48 pacientes com ES. Foram coletados dados sobre epidemiologia, manifestações clínicas e exames laboratoriais Coletou-se também o valor do HAQ. Em conclusão, manifestações articulares da ES estão associadas com pior funcionalidade e a miosite aparece nos mais jovens. Um quarto dos pacientes é positivo para fator reumatoide, mas ele não se associa com as manifestações musculoesqueléticas.

Systemic sclerosis (SSc) is a chronic and autoimmune systemic disease. It is estimated that musculoskeletal pain is present in 40-80% of patients, especially those with early diffuse disease. The objective of this work was to study the prevalence of musculoskeletal manifestations in SSc, verify if its presence alters the clinical profile, the prevalence of rheumatoid factor in SSc and its association with musculoskeletal manifestations. It is a retrospective study involving 48 patients with SSc. Data on epidemiology, clinical manifestations and laboratory tests were collected. The HAQ value was also collected. In conclusion, joint manifestations of SSc are associated with worse functionality and myositis appears in the youngest. A quarter of patients are positive for rheumatoid factor but it is not associated with musculoskeletal manifestations.

Leflunomida, ácido úrico e aterosclerose em artrite reumatoide / Leflunomide, uric acid and atherosclerosis in rheumatoid arthritis

A Artrite reumatoide (AR) é uma doença associada com aumento de risco cardiovascular em relação à população em geral. A leflunomida, utilizada para seu tratamento, tem um efeito hipouricemiante mas não se sabe se este fato influi na redução do risco cardiovascular. Objetivo: Estudar a influência do uso da leflunomida em níveis de ácido úrico sérico e na espessura da camada médio-intimal da carótida. Métodos: Sessenta pacientes com AR foram estudados: 30 usando leflunomida e 30 sem o seu uso. Dados acerca de fatores de risco cardiovascular, ácido úrico sérico e espessura da camada médio-intimal da carótida por ecografia foram obtidos. Resultado: A leflunomida mostrou-se capaz de reduzir os níveis de ácido úrico sérico (p=0.03) mas não influenciou os valores da espessura médio-intimal da carótida (p=0.51) Conclusão: Não foi possível demonstrar redução dos valores de espessura da média-íntima da carótida em pacientes usuários de leflunomida.

Background: Rheumatoid Arthritis (RA) is a disease associated with increased cardiovascular risk when compared to the general population. Leflunomide, used for its treatment, has a hypouricemiante effect but it is not known whether this fact influences the reduction of cardiovascular risk. Objective: To study the influence of the use of leflunomide in serum uric acid levels and the intimal middle layer of carotid. Methods: Sixty patients with RA were studied: 30 using leflunomide and 30 without it. Data on cardiovascular risk factors, serum uric acid and thickness of the middle-intimal layer of carotid by ultrasound were obtained. Result: Leflunomide was able to reduce serum uric acid levels (p=0.03) but did not influence the values of the medium-intimal thickness of carotid (p=0.51). Conclusion: It was not possible to demonstrate a reduction in the thickness values of the media-intima of carotid in patients using leflunomide.

Cardiovascular risk and mannose binding lectin in patients with rheumatoid arthritis from southern Brazil.

BACKGROUND: Mannose binding lectin (MBL) appears to be involved in susceptibility to rheumatoid arthritis (RA), in the inflammatory process and in the genesis of atherosclerotic disease. OBJECTIVE: To study the association of MBL serum levels and its genotypic variation with carotid arteries intimal thickness (IMT) in RA patients from Southern Brazil. METHODS: MBL serum levels, MBL2 genotyping and IMT were investigated in 90 RA patients along with their demographic, clinical and laboratory profile. MBL levels and MBL2 genotyping were evaluated in 90 healthy controls. RESULTS: A significant lower MBL serum concentration was observed in patients with RA in relation to controls (528 ng/mL vs 937.5 ng/mL, p = 0.05, respectively). The median IMT in RA patients was 0.59 mm (0.51 to 0.85 mm). There was no correlation between levels of MBL with disease activity, erythrocyte sedimentation rate, autoantibodies presence or IMT (p = NS). A weak and negative correlation was found between MBL and CRP levels (Rho = -0.24; p = 0.02;). The MBL2 variant at codon 54 (variant B) and HYPA haplotype were the most frequently observed in the RA sample (67.5% and 31.7%). MBL2 wild type (A/A) were associated with lower IMT when compared with heterozygotes (A/O; p = 0.04) and low producers (O/O; p = 0.05). In addition, high producers genotypes had lower levels of CRP when compared with medium (p = 0.04) or with low producers (p = 0.05). CONCLUSION: RA patients had lower MBL levels than controls. MBL were negatively associated with CRP serum levels; low MBL genotypes producers increased thickness of the IMT than high producers.