Predictors of serious infections in rheumatoid arthritis-a prospective Brazilian cohort.

BACKGROUND: Infections increase mortality and morbidity and often limit immunosuppressive treatment in rheumatoid arthritis patients. OBJECTIVE: To analyze the occurrence of serious infections and the associated factors in a cohort of rheumatoid arthritis patients under real-life conditions. METHODS: We analyzed data from the REAL, a prospective observational study, that evaluated Brazilian RA patients, with clinical and laboratory data collected over a year. Univariate and multivariate analyses were performed from the adjustment of the logistic regression model Generalized Estimating Equations (GEE), with the primary outcome being the occurrence of serious infection, defined as need for hospitalization or use of intravenous antibiotics for its treatment. RESULTS: 841 patients were included with an average follow-up time of 11.2 months (SD 2.4). Eighty-nine serious infections occurred, corresponding to 13 infections per 100 patient-years. Pulmonary fibrosis, chronic kidney disease (CKD) and central nervous system disease increased the chances of serious infection by 3.2 times (95% CI: 1.5-6.9), 3.6 times (95% CI: 1.2-10.4) and 2.4 times (95% CI: 1.2-5.0), respectively. The use of corticosteroids in moderate doses increased the chances by 5.4 times (95% CI: 2.3-12.4), and for each increase of 1 unit in the health assessment questionnaire (HAQ), the chance increased 60% (95% CI: 20-120%). CONCLUSION: The use of corticosteroids at moderate doses increased the risk of serious infection in RA patients. Reduced functionality assessed by the HAQ and comorbidities were other important factors associated with serious infection in this cohort.

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.

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.

Assessment of cardiovascular risk in patients with rheumatoid arthritis using the SCORE risk index.

INTRODUCTION: Rheumatoid arthritis is an autoimmune disease that causes systemic involvement and is associated with increased risk of cardiovascular disease. OBJECTIVE: To analyze the prediction index of 10-year risk of a fatal cardiovascular disease event in female RA patients versus controls. METHODS: Case-control study with analysis of 100 female patients matched for age and gender versus 100 patients in the control group. For the prediction of 10-year risk of a fatal cardiovascular disease event, the SCORE and modified SCORE (mSCORE) risk indexes were used, as suggested by EULAR, in the subgroup with two or more of the following: duration of disease ≥10 years, RF and/or anti-CCP positivity, and extra-articular manifestations. RESULTS: The prevalence of analyzed comorbidities was similar in RA patients compared with the control group (p>0.05). The means of the SCORE risk index in RA patients and in the control group were 1.99 (SD: 1.89) and 1.56 (SD: 1.87) (p=0.06), respectively. The means of mSCORE index in RA patients and in the control group were 2.84 (SD=2.86) and 1.56 (SD=1.87) (p=0.001), respectively. By using the SCORE risk index, 11% of RA patients were classified as of high risk, and with the use of mSCORE risk index, 36% were at high risk (p<0.001). CONCLUSION: The SCORE risk index is similar in both groups, but with the application of the mSCORE index, we recognized that RA patients have a higher 10-year risk of a fatal cardiovascular disease event, and this reinforces the importance of factors inherent to the disease not measured in the SCORE risk index, but considered in mSCORE risk index.

Drug survival and causes of discontinuation of the first anti-TNF in ankylosing spondylitis compared with rheumatoid arthritis: analysis from BIOBADABRASIL.

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.

[Infliximab is effective in difficult-to-control peripheral ulcerative keratitis. A report of three cases]. / Infliximabe é eficaz em ceratite ulcerada periférica de difícil controle. Um relato de três casos.

Peripheral ulcerative keratitis is caused by an inflammatory and destructive process of the perilimbal peripheral cornea. This inflammation is due to immune complex deposition in this region of the cornea and in adjacent vessels. It can be idiopathic, or a manifestation of systemic disease such as rheumatoid arthritis, vasculitis of small vessels associated with ANCA, relapsing polychondritis, systemic lupus erythematosus and Crohn's disease. Its treatment includes the use of high-dose corticosteroids and, in some cases, the concomitant use of immunosuppressants such as methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide or cyclosporine. The use of immunobiological agents can be a strategy in cases of difficult control. The authors describe the treatment of three patients who, after failure with the use of corticosteroids or immunosuppressants, showed good response after the use of infliximab.

An investigation into the relationship between anti-Helicobacter pylori and anti-Saccharomyces cerevisiae antibodies in patients with axial spondyloarthritis and Crohn disease.

Spondyloarthritis (SpA) is a musculoskeletal inflammatory disease linked with immune responses to intestinal microbiota, and subclinical intestinal ulcerations that are closely related to inflammatory bowel diseases. Helicobacter pylori is a common cause of gastroduodenal ulceration, and anti-Saccharomyces cerevisiae antibodies (ASCA) are associated with intestinal inflammation in both Crohn disease (CD) and SpA. We investigated the relationship between H. pylori and ASCA. Ninety-one patients with axial SpA and forty with CD were included. ASCA IgG/IgA and anti-H. pylori IgG titers were assessed by ELISA. The proportion of ASCA+ patients in the positive and negative anti-H. pylori IgG groups with SpA and CD were compared using Chi-square tests, and correlations were evaluated using the Spearman's coefficient. Anti-H. pylori IgG titers were significantly negatively correlated with the ASCA IgG (r = -0.563, p < 0.001) and IgA (r = -0.342, p = 0.019) titers in the axial SpA patients. The same pattern of negative correlation was also observed in the CD patients. Anti-H. pylori+ serology was significantly more frequent in axial SpA patients than in those with CD (52.4 vs. 18.4 %, p < 0.001), while ASCA+ serology was significantly more frequent in CD patients than in SpA patients. A negative correlation between the anti-H. pylori titers and ASCA was found for axial SpA and CD. Anti-H. pylori+ serology was more frequent in SpA than in CD, while ASCA positivity was more frequent in CD patients than in those with SpA. A possible influence of H. pylori on the development of ASCA needs further investigation.

Evaluation of circulating levels of inflammatory and bone formation markers in axial spondyloarthritis.

Studies have demonstrated the important role of bone remodelling and osteoimmunology in the progression of inflammatory lesions in axial spondyloarthritis (SpA) disease. This study was conducted to evaluate the inflammatory response by analysis of the serum levels of pro-inflammatory and new bone formation markers in patients with axial SpA who were treated or not treated with anti-tumour necrosis factor-α (anti-TNF-α) or non-steroidal drugs (NSAIDs) and to identify whether these drugs modify the activity and severity of the disease. The serum levels of myeloperoxidase (MPO), adenosine deaminase (ADA), nitric oxide metabolites (NOx), bone alkaline phosphatase (BAP), Dickkopf-1 (DKK-1), and osteoprotegerin (OP) were measured in 52 SpA patients who were treated or not with anti-TNF-α or NSAIDs and in 26 healthy controls using colourimetric and enzyme immunoassay tests. The activity and the severity of illness in patients with SpA were assessed using questionnaires (Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)). A significant difference between the controls and the patients without medication was observed in relation to NOx, BAP, and OP (p<0.01). When the patients were compared with regard to their treatment, there were no clinically significant differences between the groups (p>0.05). In conclusion, The NOx, BAP, and OP are emerging as important inflammatory pathways in axial SpA. Also the anti-TNF-α or non-steroidal drugs reduce the inflammation and destructions, however these treatments do not modify the serum levels of these biomarkers.

Subclinical atherosclerosis in ankylosing spondylitis: is there a role for inflammation?

OBJECTIVES: To evaluate the prevalence of subclinical atherosclerosis in patients with ankylosing spondylitis (AS) in comparison to controls with similar cardiovascular risk factors. METHODS: Forty-two consecutive patients with AS and 42 controls matched for age (43.3 ± 11.7 vs. 43.7 ± 11.3, P = 0.89), gender, smoking, diabetes mellitus and arterial hypertension were enrolled. Participants were excluded if a personal cardiovascular disease (CV) history was present. A questionnaire recording demographic data, medical and medication history was fulfilled. Blood pressure, abdominal circumference, height and weight were measured. Lipid profile was determined in a 12-hour fastened blood sample. Ultrasound analysis of the common carotid artery was performed by one blind observer. The distance between the lumen-intima interface and the leading edge of the media-adventitia interface (IMT) was measured and participants were also evaluated for the presence of plaques. RESULTS: The comparative analysis of demographic and cardiovascular risk factors between AS patients and controls did not reveal statistically significant differences. Also, no significant differences between groups were observed for TC, HDL-C, T-C/HDL-C, LDL-C, triglycerides, or dyslipidemia frequency. IMT measures were not different in AS and controls (0.62 ± 0.09 vs. 0.61 ± 0.09, P = 0.39) as well as plaques frequencies (19% vs. 17%, P = 0.78). CONCLUSIONS: Subclinical atherosclerosis assessed through carotid ultrasound imaging was not more prevalent in the AS group when compared to controls with similar cardiovascular risks. Our observations may imply that CV risk factors may have more influence on the CV system than AS itself. These findings should be confirmed in a larger population with a prospective study design.

Musculoskeletal system assessment in an emergency room.

OBJECTIVE: Musculoskeletal conditions have an enormous and growing impact worldwide. In spite of that, some clinicians are not confident in their own musculoskeletal examination skills. This study aimed to evaluate the prevalence of musculoskeletal symptoms in an emergency room, and the frequency of musculoskeletal physical examination description on those cases. METHODS: This was a cross-sectional study. We performed a systematic analysis of medical files at the emergency room of the University Hospital of the Federal University of Santa Catarina, Brazil, from April 24th to 30th, 2009. RESULTS: We analyzed 392 files, where 41.5% of patients were male and mean age was 38.7 ± 17.2 years-old. Sixty nine out of 392 patients (17.6%) presented with a musculoskeletal complaint. The most common musculoskeletal complaint was low back pain (33/69). Only 49.2% of patients with a musculoskeletal chief complaint had a specific physical examination registered on the files. Patients with musculoskeletal complaints had lower registrations of abdominal examination (46% versus 62%, P = 0.01) and vital signs (46% versus 66%, P = 0.002), but a higher frequency of musculoskeletal examination registration (49% versus 0.6%, P = 0.00). CONCLUSIONS: Our study confirms other observations worldwide. Musculoskeletal complaints are frequent in a emergency room setting and in spite of that it is suggested that musculoskeletal symptoms are poorly evaluated, which is probably related to an insufficient musculoskeletal education. It is essential that medical schools place more emphasis on these conditions so that young physicians will be more prepared to deal with these common diseases.

Takayasu arteritis: anti-TNF therapy in a Brazilian setting.

The aim of this study was to describe clinical features and response to different therapeutic interventions, including anti-tumor necrosis factor (TNF) agents, in a case series of Takayasu arteritis (TA) from Brazil. A retrospective observational chart-review study was performed including all patients meeting the American College of Rheumatology TA classification criteria followed at the rheumatology outpatient clinic of a Brazilian university hospital. Fifteen patients were included, of which 14 (93.3%) were females, with a mean age of 29.6 years at diagnosis. Systemic hypertension (60.0%) and abolished upper limb pulses (53.3%) were the most common clinical features at the diagnosis. Subclavian and carotid arteries were the most commonly affected vessels. Twelve patients (80.0%) did not achieve sustained remission on therapy with corticosteroids alone and received immunosuppressive agents including methotrexate, azathioprine and cyclophosphamide. Surgical intervention was necessary and performed in 53.3% of cases. Three cases (20.0%) were refractory to corticosteroid plus diverse immunosuppressive therapy and were treated with anti-TNF agents, all of them with disease remission. In conclusion, a significant proportion of TA cases are refractory to traditional therapy. The use of anti-TNF agents may become a possible therapy for these patients.

Reinforcing a medical hypothesis with a new question: is there a subgroup of shrinking lungs syndrome that is induced by pleurisy in systemic lupus erythematosus and is this subgroup marked by anti-Ro/SSA?

Shrinking lungs syndrome (SLS) is a rare entity associated with autoimmune diseases and its underlying pathogenesis is still unclear. We describe a series of seven consecutive cases of SLS in systemic lupus erythematosus, all of them with serositis and six (85.7%) with anti-Ro/SSA antibodies. Our findings reinforce the hypothesis that SLS may be, in some cases, a consequence of diaphragmatic restriction due to pleuritic pain, and we suggest anti-Ro/SSA as a marker of this subgroup of SLS.