Tumor Necrosis Factor Alpha (TNF-a) Blockade and Risk of Lymphoma: Systematic Review and Analysis of Literature

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5278-5278
Author(s):  
Jeyanthi Ramanarayanan ◽  
Shalu Pahuja ◽  
Myron S Czuczman ◽  
Francisco J. Hernandez-Ilizaliturri
Keyword(s):  
Rheumatoid Arthritis ◽  
English Language ◽  
Critical Role ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Inflammatory Disorders ◽  
Number Of Patients ◽  
Increased Risk ◽  
Tnf Α

Abstract BACKGROUND: TNF-α plays a critical role in the regulation of cytokine mediated cancer immunosurveillance. Evidence suggests that depletion of TNF-α may result in abrogated anti-tumor immunity and increase in the risk of malignancies. Anti-TNF-α therapy (infliximab, adalimumab and etanercept) is known to halt the progression of certain inflammatory disorders and has been approved for the treatment of at least five autoimmune/inflammatory conditions. Given the widespread use of these biological agents, it is vital to explore the associated increased risk of malignancies especially lymphoma. OBJECTIVE: Risk of lymphoma associated with anti-TNF-α therapy is controversial in rheumatoid arthritis (RA) and has not been extensively studied in other inflammatory disorders. With the expanding role of anti-TNF-α therapy, we evaluated the risk of lymphoma among all approved indications for which they are currently in use. METHODOLOGY: We conducted a systematic electronic search of MEDLINE using the terms TNF-α, infliximab, adalimumab, etanercept, rheumatoid, psoriasis, arthritis, inflammatory bowel disease, ankylosing spondylitis from January 1998 to December 2007. Studies analyzed were restricted to those in English language, full text published articles, randomized controlled trials (RCT), meta-analysis (MT), review articles, extension studies, reports from national databases (ND) and postmarketing surveillance studies. Risk of lymphoma from ND was obtained as odds ratio with 95% confidence interval. Incidence of lymphoma reported from RCT was analyzed as percentage fraction of the total number of patients enrolled in the study and follow up. RESULTS: Overall 51 studies (2 MT, n=10,370; 4 ND, n=29,099 and 45 RCT, n=54,637) that included anti-TNF-α therapy in inflammatory disorders were analyzed. Treatment/follow up period were variable from 12 weeks to 8 years. Ten patients (0.09%) from MT treated with anti-TNF-α therapy developed lymphoma vs 0 in the non-anti-TNF-α group. Report from one of the 3 ND showed an increased risk (11.5 RR 95% CI 3.7–26.9) of lymphoma among the anti-TN-α exposed group. Among the RCT, 16 patients (0.02%) in the anti-TNF-α group developed lymphoma vs 3 (0.005%) in the control group. CONCLUSION: Existing data suggests that anti-TNF-α therapy in rheumatoid arthritis is associated with an increased risk of lymphoma but this may be attributed to the severity of the disease itself. Among other inflammatory disorders, a rise in lymphoma risk could not be established. Whether anti-TNF-α therapy in the long term can in fact decrease the incidence of lymphoma by altering the disease severity remains to be determined.

scholarly journals Increased Risk of Temporomandibular Joint Disorder in Patients with Rheumatoid Arthritis: A Longitudinal Follow-Up Study

2020 ◽  
Vol 9 (9) ◽  
pp. 3005
Author(s):  
Soo-Hwan Byun ◽  
Chanyang Min ◽  
Hyo-Geun Choi ◽  
Seok-Jin Hong
Keyword(s):  
Rheumatoid Arthritis ◽  
Temporomandibular Disorder ◽  
Population Data ◽  
Control Group ◽  
Chi Square ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Joint Disorder

We evaluated the incidence of temporomandibular disorder (TMD) in patients with rheumatoid arthritis (RA) and examined the association between TMD and RA, through longitudinal follow-up. Population data from the Korean National Health Insurance Service-Health Screening Cohort from 2002 to 2015 was used. From 514,866 subjects, 3122 with RA were matched with 12,488 controls in a 1:4 ratio. The crude and adjusted models (for obesity, smoking, alcohol consumption, blood pressure, blood glucose, total cholesterol, and Charlson Comorbidity Index scores) were calculated. Chi-square tests, Kaplan-Meier (KM) analysis, and two-tailed analyses were used for statistical analysis. Stratified Cox proportional hazard models were used to assess the hazard ratios (HR) and 95% confidence intervals (CI) for TMD in the RA group, compared to those in the control group. The adjusted HR for TMD in RA was 2.52 (95% CI = 1.70–3.74), compared to the control group. The results were consistent with the subgroup analyses, according to age and sex, except in men older than 60 years of age. KM analysis showed similar results. Hence, we found that patients with RA have a higher risk of TMD, and should be observed for symptoms of the initial stage of TMD to prevent the risk of aggravation.

scholarly journals IMMUNOGENICITY AND SAFETY OF 23-VALENT POLYSACCHARIDE PNEUMOCOCCAL VACCINE IN PATIENTS WITH RHEUMATOID ARTHRITIS: RESULTS OF A TWO-YEAR FOLLOW-UP STUDY

2017 ◽  
Vol 54 (6) ◽  
pp. 674-680 ◽  
Author(s):  
M. S. Naumtseva ◽  
B. S. Belov ◽  
E. N. Aleksandrova ◽  
G. M. Tarasova ◽  
A. A. Novikov ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Enzyme Immunoassay ◽  
Pneumococcal Vaccine ◽  
Control Group ◽  
Inflammatory Rheumatic Diseases ◽  
Low Grade ◽  
Follow Up Study ◽  
Tnf Α ◽  
Polysaccharide Pneumococcal Vaccine

Objective: to investigate the immunogenicity, safety, and clinical efficacy of 23-valent polysaccharide pneumococcal vaccine in patients with rheumatoid arthritis (RA) during a two-year follow-up study.Subjects and methods. The prospective open-label comparative study enrolled 110 people, of them there were 81 (73.6%) women and 29 (26.4%) men at the age of 23 to 76 years, including 79 patients with RA, as well as 31 subjects without systemic inflammatory rheumatic diseases (RD) (a control group). The group of RA patients exhibited a predominance of middle-aged women who had > 3 years’ disease duration and a moderate inflammatory activity (the mean value of DAS28, 4.32). 52 patients received methotrexate (MTX), 14 had Leflunomide (LEF), and 13 were treated with tumor necrosis factor-α (TNF-α) inhibitors + MTX.The 23-valent polysaccharide pneumococcal vaccine Pneumo-23 (Sanofi Pasteur, France) was administered in a single dose of 0.5 ml subcutaneously during continuous MTX or LEF therapy for the underlying disease or 3–4 weeks before the use of TNF-α inhibitors. Clinical examinations of the patient and conventional clinical and laboratory studies were performed during control visits (1, 3, 12, and 24 months after vaccination). Clinical effectiveness and safety were evaluated in all the patients included in the study. The serum levels of anti-pneumococcal capsular polysaccharide antibodies (Ab) were measured in 72 patients with RA and in 30 individuals in the control group during a 12-month follow-up study, including in 25 patients with RA for a 24-month follow-up study by enzyme immunoassay using commercial VaccZymeTM Anti-PCP IgG Enzyme Immunoassay kits (The Binding Site Group Ltd, Birmingham, United Kingdom). Along with this, the post-immunization response coefficient was calculated for each patient as the ratio of postvaccination Ab levels during Visits 2, 3, 4, and 5 to the baseline Ab level.Results and discussion. No clinical and radiological symptoms of pneumonia were recorded in any case during the follow-up period. The patients with RA and the control group showed a more than double significant increase of anti-pneumococcal Ab level during 3 months following vaccination. Despite the decrease in their concentration by month 12, the latter remained at the appropriate level and significantly increased at 24-month follow-up. Vaccination was well tolerated. A favorable course of the postvaccinal period was noted in all cases. There were no adverse reactions to vaccination in 72 (65%) patients; 38 (35%) patients were noted to have pain, skin swelling and hyperemia up to 2 cm in diameter at the site of injection, as well as low-grade fever. There were no episodes of a RD exacerbation or any new autoimmune disorders during the follow-up period.Conclusion. The findings were suggestive of the sufficient immunogenicity and good tolerability of 23-valent pneumococcal vaccine in patients with RD during the two-year follow-up period.

Analysis Of a Single Institutional Cohort Of 20,593 Patients Tested For Antiphospholipid Antibodies Indicates Significant Prospective Risk For Thrombosis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2366-2366
Author(s):  
D. Yitzchak Goldstein ◽  
Jacob Rand ◽  
Lucia R Wolgast
Keyword(s):  
Information System ◽  
Antiphospholipid Antibodies ◽  
Thrombotic Event ◽  
Tertiary Care ◽  
Control Group ◽  
P Value ◽  
Care Organization ◽  
Number Of Patients ◽  
Increased Risk

Abstract Background Quantification of the risk associated with positive antiphospholipid (aPL) antibodies has been problematic since previous assessments have relied on observing relatively small study populations or meta-analyses of collected larger groups. There would be a significant benefit to a tool that would permit analysis of clinical outcomes of large patient cohorts. We applied a novel analytical information system, named “Clinical Looking Glass” (CLG), which aggregates clinical, diagnostic, therapeutic and outcomes data from a single large academic health care center to address this question. Methods CLG was employed to collect all patients at a large tertiary care institution for whom antiphospholipid antibodies including lupus anticoagulant (LAC), anticardiolipin (aCL) antibodies and anti- β2-glycoproteinI (aβ2GPI) were performed. The immunoassays were grouped by isotype and values of >30U/L (>99th percentile) were considered positive. An untested control group was derived from outcomes data on all institutional Pioneer Accountable Care Organization patients, a cohort, whose coordinated care is managed by a single institution, permitted accurate and robust follow-up data. We used the CLG to track patients for a period of 583 days (maximum data available for control group) following their individual test results to identify a predefined thrombotic outcome. The outcome was defined by any encounter (inpatient, outpatient or ED), subsequent to the initial lab value date, which demonstrated a new thrombotic event. Results Using CLG we were able to evaluate 20,593 unique patients who had some form of LA testing performed. The aCL assays were performed on the greatest number of patients (18,201) followed by the LAC (11,267) with the fewest number of patients tested for aβ2GPI (7,914). A total of 5,660 patients had testing for all three. Of all 11,267 patients having LAC testing performed, 754 patients had at least one positive result. Of these 25.9% went on to develop a thrombotic event during the follow-up period compared to 15.0% of LAC negative patients (p value <0.001) and only 1.64% of the ACO control group suffering an event (p value <0.001). The relative risk associated with LAC positivity over the control group was 14.75 (95% CI 13.6-19.1). All other APL antibodies also demonstrated statistically increased risk of thrombosis over the examined cohort control (RR ranging from 6.6-11.2), but each of these to a significantly lesser degree than when compared directly to the LAC (results summarized in adjoining table and graph). Conclusions This first large study of aPL assays with prospective data from a single clinical information system confirms previous observations from smaller studies that LAC is the most significant laboratory predictor of future thrombotic events. However, in contrast to previous studies, all aPL antibodies, including IgA, demonstrated a statistically increased risk over a control population with LAC positivity having statistically greater risk than all others. Interestingly, aCL IgM was the weakest predictor of a future thrombotic event. Additionally we demonstrate the utility of clinical analytical software tools to offer very powerful ways to test prior assumptions and obtain novel results on large cohorts of patients in “real world” settings. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Evaluation of efficacy and safety of long-term use of amtolmetin guacil in rheumatic diseases: results of a 9-month observational AURORA study (Amtolmetin guacil: allRussian Register for Osteoarthritis, Rheumatoid arthritis and Ankylosing spondylitis)

2019 ◽  
Vol 57 (1) ◽  
pp. 66-74
Author(s):  
A. E. Karateev ◽  
E. L. Nasonov ◽  
S. I. Glukhova ◽  
A. A. Barakat ◽  
R. L. Gibadullina ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Rheumatic Diseases ◽  
Rating Scale ◽  
Term Therapy ◽  
Control Group ◽  
Number Of Patients ◽  
Long Term Treatment

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the treatment of rheumatic diseases (RD). In some cases, their long-term use is advisable: NSAIDs slow the progression of spondylarthritis, are an important element in the control of chronic pain in osteoarthritis (OA) and rheumatoid arthritis (RA). However, the risk of serious adverse events (AE) should be considered. A good choice for long-term therapy may be amtolmetin guacil (AMG), which rarely induce gastrointestinal AE.The aimof the study was to assess the effect and safety of long-term use of AMG in RD.Material and methods.An open observational study was conducted in which AMG (Nayzilat) was assigned to 442 patients with OA (mean age 60.6±10.2 years, women 88.7%), 126 patients with RA (55.0±14.0 years, women 84.2%) and 73 with ankylosing spondylitis (AS, 47.0±12.0 years, women 30.0%). The dose of AMG depended on the clinical situation and was determined by the attending physician: from 1800 to 600 mg/day. The main criterion of the effect was the changes of pain by numeric rating scale (NRS), additional measures of efficacy were pain on the WOMAC and HAQ for OA, DAS28 for RA, BASDAI, BASFI and ASDAS-CRP for AS. The result of treatment was evaluated during three consecutive visits every 3 months (9 months of follow-up).Results and discussion.At the end of follow-up 65.2% of patients with OA, 75.3% of patients with RA and 82.2% of patients with AS continued treatment with AMG. The reasons for discontinuation of treatment were significant reduction or absence of pain (70.3%), the patient's decision (26.6%) or AE (3.1%). At the end of follow-up, there was a significant decrease in pain intensity compared to the baseline: in OA, the median pain decreased from 5.6 [4.1; 6.9] to 3.4 [1.7; 5.1], in RA from 5.8 [4.0; 7.5] to 3.4 [2.0; 4.8], in AS from 5.8 [4.2; 7.5] to 3.1 [1.5; 5.0] according to NRS, the difference was significant in all groups (p<0.001). In OA, the median WOMAC pain decreased from 127 [24; 159] to 13.7 [14; 40] (p<0.001), the average HAQ value – from 0.54±0.44 to 0.34±0.26 (p<0.001). In RA, the average value of DAS28 decreased from 4.81±1.18 to 4.30±1.24 (p<0.05). The number of painful and swollen joints, ESR and C-reactive protein also significantly decreased. In AS, the median BASDAI index decreased from 4.5 [1.0; 8.0] to 3.0 [0; 8.0] (p<0.001). The number of patients with high activity according to ASDAS-CRP (>3.5) decreased from 76.9 to 25.8% (p<0.001). The BASFI index did not changed. 77.9% of patients with OA, 77.0% with RA and 74.5% with AS were satisfied with the results of AMG treatment. AMG tolerance was good. Mild dyspepsia was observed in 15–25% of patients. AE, which caused the discontinuation of therapy, were observed only in 6 (0.93%) patients. There was no development or deterioration of hypertension, as well as other cardiovascular complications.Conclusion.AMG is an effective NSAID with good tolerability, which is advisable to use for long-term treatment of RD. Limitations are the open nature of the study and the absence of a control group.

Autoantibody profiling in patients with very early rheumatoid arthritis: a follow-up study

2009 ◽  
Vol 69 (01) ◽  
pp. 169-174 ◽  
Author(s):  
V Nell-Duxneuner ◽  
K Machold ◽  
T Stamm ◽  
G Eberl ◽  
H Heinzl ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Final Diagnosis ◽  
Early Arthritis ◽  
Erosive Disease ◽  
Follow Up Study ◽  
Number Of Patients ◽  
Increased Risk ◽  
Time Courses ◽  
Citrullinated Peptide

Objective:To investigate time courses of autoantibody profiles in patients with early arthritis.Patients and methods:A total of 200 patients with very early arthritis (<3 months duration), among them 102 patients with a final diagnosis of rheumatoid arthritis (RA) and 98 with other rheumatic diseases, were followed up for several years. First follow-up testing was performed in all patients (mean 5 months from baseline), and 82 patients with RA and 35 patients without RA were available for last follow-up testing (mean 32 months from baseline). IgM-rheumatoid factor (RF) was measured by nephelometry, IgA-RF, IgG-RF and anti-cyclic citrullinated peptide antibodies (ACPA) by ELISA, and anti-RA33 antibodies were determined by immunoblotting.Results:At baseline, IgA-RF was detectable in 29% and IgG-RF in 14% of patients with RA while IgM-RF>50 IU/ml (RF50) was positive in 45% of the patients; specificities were 97%, 99% and 96%, respectively. However, the vast majority of patients positive for IgA-RF or IgG-RF were also positive for RF50 or ACPA. During follow-up, the prevalence of ACPA slightly increased while prevalence of all RF subtypes and anti-RA33 decreased. Remarkably, the number of patients positive for RF50 and/or ACPA remained constant, and these patients had a highly increased risk for developing erosive disease in contrast to patients solely positive for anti-RA33.Conclusions:Testing for RF subtypes did not provide additional diagnostic information. Patients positive for RF50 and/or ACPA had an unfavourable prognosis, irrespectively of changes in the antibody profile during follow-up, whereas anti-RA33 positivity was inversely associated with erosiveness at baseline and at later time points.

scholarly journals The Use of 23-Valent Pneumococcal Polysaccharide Vaccine in Patients with Rheumatoid Arthritis

2015 ◽  
Vol 14 (4) ◽  
pp. 67-73
Author(s):  
M. S. Naumtseva ◽  
B. S. Belov ◽  
G. M. Tarasova ◽  
D. E. Karateev ◽  
E. L. Luchikhina ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Efficacy ◽  
Pneumococcal Vaccine ◽  
Fold Increase ◽  
Control Group ◽  
Inflammatory Rheumatic Diseases ◽  
Good Tolerability ◽  
Tnf Α ◽  
Tract Infections

Objective: to study the clinical efficacy, immunogenicity, and safety of a 23-valent pneumococcal vaccine in patients with rheumatoid arthritis (RA).Subjects and methods. The investigation enrolled 102 patients (78 women and 24 men, aged 23 – 70 years), including 72 patients with RA and 30 people without systemic inflammatory rheumatic diseases (a control group) who had a recent history of 2 and more cases of lower respiratory tract infections (bronchitis, pneumonia). When included, all the patients received anti-inflammatory therapy with methotrexate (MT) (n = 52), leflunomide (LEF) (n = 10), or MT + tumor necrosis factor-α (TNF-α ) inhibitors (n = 10). A single 0.5-ml dose of the 23-valent pneumococcal vaccine was administered subcutaneously during continuous MT or LEF therapy for the underlying disease or 3 – 4 weeks before the use of a TNF-α inhibitor. During control visits (1 and 3 months and 1 year after administration of the vaccine), the patients underwent physical examination and routine clinical and laboratory studies.Results. No clinical and radiological symptoms of pneumonia were recorded in any case during a 12-month follow-up. The RA and control groups showed a more than 2-fold increase in anti-pneumococcal antibody levels 1 year after vaccination. The vaccine was well tolerated by 67 patients. 27 patients were observed to have pain, cutaneous swelling and hyperemia and 8 patients had subfebrility. There were neither episodes of RA exacerbation nor new autoimmune disorders during the follow-up.Conclusion. The findings suggest that 23-valent pneumococcal vaccine shows a good clinical efficacy, adequate immunogenicity, and good tolerability in the patients with RA. 

scholarly journals Association between ischemic stroke and seropositive rheumatoid arthritis in Korea: A nationwide longitudinal cohort study

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251851
Author(s):  
Dong Hyun Lee ◽  
Seung Hun Sheen ◽  
Dong-Geun Lee ◽  
Jae-Won Jang ◽  
Dong Chan Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ischemic Stroke ◽  
Hazard Ratio ◽  
Control Group ◽  
Medical Disorders ◽  
Seropositive Rheumatoid Arthritis ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Age And Sex

The purpose of this longitudinal follow-up study was to investigate the risk of ischemic stroke nationwide in patients with seropositive rheumatoid arthritis (RA) and controls who were matched in age and sex. Patient data were collected from the National Health Insurance Service (NHIS) Health Screening (HEALS) cohort. Using the International Classification of Diseases code M05 (seropositive RA), with a prescription of any disease-modifying anti-rheumatic drug (DMARD), RA was identified. A total of 2,765 patients and 13,825 control subjects were included in our study. The 12-year incidence of ischemic stroke in each group was calculated using the Kaplan–Meier method. The risk ratio of ischemic stroke was estimated using Cox proportional hazards regression. Sixty-four patients (2.31%) in the seropositive RA group and 512 (3.70%) in the control group experienced ischemic stroke (P < 0.001) during the follow-up period. The hazard ratio of ischemic stroke in the seropositive RA group was 1.32 (95% confidence interval (CI), 1.02–1.73) after adjusting for age and sex. The adjusted hazard ratio of ischemic stroke in the seropositive RA group was 1.40 (95% CI, 1.07–1.82) after adjusting for demographics and comorbid medical disorders. According to the subgroup analysis, the hazard ratios of ischemic stroke risks in the female and hypertensive subgroups were 1.44 (95% CI, 1.05–1.97) and 1.66 (95% CI, 1.16–2.38), respectively. In the non-diabetes and non-dyslipidemia subgroups, the corresponding hazard ratios of ischemic stroke were 1.47 (95% CI, 1.11–1.95) and 1.43 (95% CI, 1.07–1.91). Seropositive RA patients have an increased risk of ischemic stroke. In female, hypertension, non-diabetes, and non-dyslipidemia RA subgroups, even without the traditional risk factors for stroke (except for hypertension), increased the risk, which could be potentially attributed to RA.

scholarly journals Risk factors for recurrent wheezing after bronchiolitis in infants: 2-year follow up in China

2020 ◽  
Author(s):  
Sainan Chen ◽  
Wenjing Gu ◽  
Min Wu ◽  
Chuangli Hao ◽  
Canhong Zhu ◽  
...  
Keyword(s):  
Risk Factor ◽  
Independent Risk Factor ◽  
Severe Disease ◽  
Serum Levels ◽  
Control Group ◽  
Healthy Children ◽  
Recurrent Wheezing ◽  
Increased Risk ◽  
Tnf Α

Abstract Background: Infants with bronchiolitis have an increased risk of developing recurrent wheezing and asthma. However, the association between bronchiolitis and recurrent wheezing remains controversial.Objective: To investigate the incidence of post-bronchiolitis recurrent wheezing and associated risk factors.Methods: Infants with bronchiolitis were enrolled from November 2016 through March 2017. We also enrolled 24 healthy children with no history of wheezing from the department of children's health prevention as a control group. Nasopharyngeal aspirates were obtained for detection of respiratory viruses which were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and direct immunofluorescent assay. Serum cytokines including TSLP, IL2, IL13, TIMP-1, MMP-9, IL33, IL5, IL4, IL25, TNF- α and MIP-1α were measured by flow cytometry. Patients were followed every 3 months for a duration of 2 years by telephone or at outpatient appointments.Results: We enrolled 89 infants, of which 81 patients were successfully followed up. In total, 22.2% of patients experienced recurrent wheezing episodes. The proportion of patients with eczema, systemic glucocorticoid use and patients with moderate-to-severe disease were significantly higher in the recurrent wheezing group than the non-recurrent wheezing group (83.3% vs 52.4%; 66.7% vs 36.5%; 61.1% vs 33.3%, respectively, all P<0.05); The serum level of TNF‑ α was lower in the recurrent wheezing group (P<0.05), and the serum levels of IL-4, IL-5, IL-25, IL-33 were significantly higher among patients without recurrent wheezing (P<0.05). Logistic regression analysis showed that eczema was an independent risk factor for post-bronchiolitis recurrent wheezing (odds ratio [OR]=7.488; 95% confidence interval [CI], 1.447–38.759; P=0.016). Conclusion: The incidence of recurrent wheezing among infants after contracting bronchiolitis was 22.2% during a 2-year follow-up. Eczema was the only independent risk factor identified and no correlation was found between the specific virus and disease severity in children with post-bronchiolitis recurrent wheezing.

scholarly journals POS0488 THE IMPACT OF ANTINUCLEAR ANTIBODIES INDUCED BY ANTI-TUMOUR NECROSIS FACTOR ALPHA AGENTS ON THE LONG-TERM TREATMENT OUTCOMES IN RHEUMATOID ARTHRITIS PATIENTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 476.2-477
Author(s):  
D. Santos Oliveira ◽  
A. Martins ◽  
F. R. Martins ◽  
M. Rato ◽  
F. Oliveira Pinheiro ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Response ◽  
Response To Treatment ◽  
Eular Response ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Switch Rate ◽  
Factor Alpha ◽  
The Impact

Background:The seroconversion of antinuclear antibodies (ANA) induced by anti-tumour necrosis factor alpha (anti-TNF-α) therapy remains a matter of concern in various inflammatory conditions namely rheumatoid arthritis. However, evidence is still scarce regarding the impact of these autoantibodies on the clinical response to treatment in these patients.Objectives:This study aimed to explore the impact of ANA induced by anti-TNF-α therapy on the outcomes of treatment in patients with rheumatoid arthritis over two years of follow-up.Methods:An observational retrospective cohort study was conducted with two years of follow-up. Patients diagnosed with rheumatoid arthritis, according to the American College of Rheumatology (ACR) criteria, and registered on the Rheumatic Diseases Portuguese Register (Reuma.pt) who started their first anti-TNFα agent as first biologic between 2003 and 2018 were included. Patients with positive ANA (titer ≥100) and/or positive anti-double stranded DNA (anti-dsDNA) antibodies and/or with a diagnosis of SLE at their first visit were excluded. Demographic, clinical and laboratory data were obtained by consulting Reuma.pt. Disease Activity Score for 28 joints (DAS28), DAS28 delta, Health Assessment Questionnaire (HAQ), HAQ delta were assessed at baseline, 6, 12, 18 and 24 months. Clinical response was evaluated by EULAR criteria and three response categories were defined: good, mild and no response. The rate of switch of biological treatment was assessed over 24 months. To examine the differences between groups with and without ANA seroconversion independent samples t test for normally distributed continuous data, Mann-Whitney U-tests for non-normally distributed continuous data and Chi-square tests for categorical data were used. Logistic regression models were used to assess the effects of ANA seroconversion on clinical response to treatment over 6, 12, 18 and 24 months.Results:A total of 185 patients (mean age of 49.3±10.9 years old; 85.4% female) with a median follow-up of 7 [4-14] years were included. We found an ANA seroconversion rate (titer ≥100) of 77.3% (n=143) with median time of 36 [15-72.3] months. There were no differences among groups regarding age, gender, disease duration, be seropositivity or not (for rheumatoid factor and/or anti-citrullinated protein antibodies) and have an erosive disease or not. DAS28 delta was significantly different (p=0.035) between group with positive ANA (2.01±1.29) and negative ANA (1.15±1.51) at 6 months. DAS28 was significantly different (p=0.014) between group with positive ANA (5.06±3.39) and negative ANA (3.99±1.43) at 12 months. No statistically significant differences were found in the DAS28, DAS28 delta, HAQ, HAQ delta at 18 and 24 months and in the EULAR response at any time. Switch rate was significantly different between patients with ANA seroconversion (median 1[0-1]) versus absence of seroconversion (median 0[0-1]), p=0.025. In the regression model ANA seroconversion did not predict switch rate and EULAR response over time.Conclusion:This study showed that the majority of patients with rheumatoid arthritis treated with an anti-TNF-α agent developed ANA and that their presence may be associated with worse clinical results (DAS28) at 6 and 12 months. In fact, previous research suggested that a decrease in anti-TNF-α drug concentration due to the production of autoantibodies may lead to worse outcomes of treatment. Moreover, our data demonstrated that patients with ANA seroconversion had a higher switch rate. Despite these results, there are no differences in the EULAR response between the two groups and ANA seroconversion did not predict this response over time. Therefore, ANA induced by anti-TNF-α agents should be monitored in patients with rheumatoid arthritis and its impact on treatment must be considered. Further research is needed to explore these results through large-scale prospective studies.Disclosure of Interests:None declared

Comparative analysis of polymorphic variants of IL-17A and MMP-1 genes with the risk of developing chronic periodontitis in petrochemical workers

2020 ◽  
Vol 60 (10) ◽  
pp. 687-693
Author(s):  
Iskander I. Zaidullin ◽  
Denis O. Karimov ◽  
Lilija K. Karimova ◽  
Milyausha F. Kabirova ◽  
Rasima R. Galimova ◽  
...  
Keyword(s):  
Ethylene Oxide ◽  
Chronic Periodontitis ◽  
Periodontal Diseases ◽  
Clinical Manifestations ◽  
Control Group ◽  
Periodontal Tissues ◽  
Dental Examination ◽  
Number Of Patients ◽  
Increased Risk ◽  
Harmful Substances

The susceptibility to the development and progression of inflammatory periodontal diseases, which depends on genetic and external factors (smoking, stress, oral hygiene), varies widely. In the development of these diseases, an important role is played not only by the presence of periodontal pathogenic microorganisms, but also by the presence of congenital or acquired immunodeficiency, immunoregulatory defects. The immune system plays a key role in the physiological and pathological processes of periodontal tissues. In this regard, IL17, produced by CD4+ Th cells, which has both Pro-inflammatory and protective activity, is of particular interest in the pathogenesis of periodontitis. The aim of study was to identify the relationship between polymorphic loci of the IL-17A (rs2275913) and MMP-1 (rs1799750) genes and clinical manifestations of chronic periodontitis in petrochemical workers. Dental examination was performed in 92 ethylene oxide production workers with chronic periodontitis and 74 patients with chronic periodontitis who did not come into contact with chemical factors (control group). Genotyping of polymorphisms rs2275913 of the IL17A gene and rs1799750 of the MMP1 gene was performed by allele-specific real-time polymerase chain reaction (PCR). Hygienic assessment of the degree of air pollution of the working area with harmful substances was carried out by gas chromatography according to the guidelines for the determination of harmful substances in the air № 5098-89, № 3119-84. When comparing the results of studies of both groups, there were no statistically significant differences in the frequency distributions of allelic variants and genotypes of the IL-17A and MMP-1 genes. The AA/AG genotypes of the IL-17A gene were associated with an increased risk of severe disease compared to the GG genotype in workers in the main group (OR=6.1; 95% CI 1.33-28.5; p=0.021) and in the control group (OR=7.26; 95% CI 1.34-39.25; p=0.016). Carriers of the A allele in the control group increased the risk of severe chronic periodontitis by 2.4 times compared to carriers of the G allele (OR=2.41; 95% CI 1.19-4.87; p=0.014). During the dental examination of employees of the ethylene oxide plant, the clinical course of periodontal diseases was more severe in comparison with the control group, and the number of patients with severe periodontitis was twice as high. It was found that the AA/AG genotypes of the IL-17A gene and the carrier of the A allele are associated with increased susceptibility to the development of severe chronic periodontitis. The association between the MMP-1 gene polymorphism and the risk of severe forms of chronic periodontitis has not been established. A risk factor for the development of inflammatory periodontal diseases in employees of the petrochemical complex is a complex of harmful production factors.

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