anti-TNF Treatment Research Articles

Association between ustekinumab therapy and changes in specific anti-microbial response, serum biomarkers, and microbiota composition in patients with IBD: A pilot study.

Ustekinumab, is a new therapy for patients with IBD, especially for patients suffering from Crohn's disease (CD) who did not respond to anti-TNF treatment. To shed light on the longitudinal effect of ustekinumab on the immune system, we investigated the effect on skin and gut microbiota composition, specific immune response to commensals, and various serum biomarkers. We recruited 11 patients with IBD who were monitored over 40 weeks of ustekinumab therapy and 39 healthy controls (HC). We found differences in the concentrations of serum levels of osteoprotegerin, TGF-β1, IL-33, and serum IgM antibodies against Lactobacillus plantarum between patients with IBD and HC. The levels of these biomarkers did not change in response to ustekinumab treatment or with disease improvement during the 40 weeks of observation. Additionally, we identified differences in stool abundance of uncultured Subdoligranulum, Faecalibacterium, and Bacteroides between patients with IBD and HC. In this preliminary study, we provide a unique overview of the longitudinal monitoring of fecal and skin microbial profiles as well as various serum biomarkers and humoral and cellular response to gut commensals in a small cohort of patients with IBD on ustekinumab therapy.

Does Late Axial Spondyloarthropathy Diagnosis Cause Extra Anti-TNF Therapy?

Introduction: Ankylosing Spondylitis (AS) is a chronic inflammatory rheumatic disease that mainly characterized by sacroiliac joint and spine involvement. Although there is no clear evidence that any of these agent prevent the radiologic progression, anti-TNF drugs provide significant improvements in the disease activity score, functional index and quality of life. In AS patients, knowledge of the factors that determine the need for anti-TNF treatment will be associated with fewer complication sand better treatment. The purpose of this study is to investigate the possible factors which willmark the transition to the anti-TNF therapy in AS patients. Materials and Methods: This study was conducted in the Rheumatology division of the Internal medicine department of the Ondokuz Mayis University of Medicine hospital between January 2012- June 2015. The study protocol was approved by the Ethics Committee of Ondokuz Mayis University. A total of 165 patients, who were diagnosed as AS according to the ASAS classification criteria, were enrolled in this study. There were 85 women (51.5%) and 80 men (48.5%), aged between 15-69. Patients were divided into two groups according to their use of anti-TNF drug. Results: A total of 165 Ax-SpA patients (85 women and 80 men) were included in the study. The mean age was 37.82±11.24 years. The mean duration of the disease was 4.59±5.35 years. male gender, uveitis, delay in diagnosis, elevations in sedimentation CRP levels, increase in disease activity and functional indexes such as BASDAI and BASFI scores shows the more frequent need for anti-TNF drug use. Conclusion: In our study, patients who needed anti-TNF treatment had a longer time between symptom onset and diagnosis than patients who did not hear. The delay in diagnosing these patients leads to a delay in treatment so that the focus of inflammation increases and these patients need more anti-TNF as this window of opportunity escapes.

Anti-TNF Treatment in Crohn’s Disease Complicated by Intra-abdominal Abscess

Excess production of TNF-α leads to chronic inflammation and tissue damage in immune-mediated inflammatory diseases (IMID) such as Crohn’s Disease (CD), rheumatoid arthritis, and psoriasis. The introduction of anti-TNF agents revolutionised therapy for patients with IMIDs, and two anti-TNFs are currently approved for use in CD in Europe: infliximab and adalimumab. The chronic transmural inflammation associated with CD commonly leads to intestinal complications such as intra-abdominal abscesses, which present a challenge to a multidisciplinary medical team. While surgical management may ultimately be required in some patients, it is associated with a risk of morbidity and loss of function, particularly in a patient who requires immunosuppression to address their underlying CD. This mini review summarises the current evidence surrounding the use of anti-TNFs in CD complicated by intra-abdominal abscess, including current treatment guidelines, the use of anti-TNFs in combination with conservative (non-surgical) management, and the impact of anti-TNFs on post-operative complications and abscess recurrence.

Specific S100 Proteins Bind Tumor Necrosis Factor and Inhibit Its Activity.

Tumor necrosis factor (TNF) inhibitors (anti-TNFs) represent a cornerstone of the treatment of various immune-mediated inflammatory diseases and are among the most commercially successful therapeutic agents. Knowledge of TNF binding partners is critical for identification of the factors able to affect clinical efficacy of the anti-TNFs. Here, we report that among eighteen representatives of the multifunctional S100 protein family, only S100A11, S100A12 and S100A13 interact with the soluble form of TNF (sTNF) in vitro. The lowest equilibrium dissociation constants (Kd) for the complexes with monomeric sTNF determined using surface plasmon resonance spectroscopy range from 2 nM to 28 nM. The apparent Kd values for the complexes of multimeric sTNF with S100A11/A12 estimated from fluorimetric titrations are 0.1-0.3 µM. S100A12/A13 suppress the cytotoxic activity of sTNF against Huh-7 cells, as evidenced by the MTT assay. Structural modeling indicates that the sTNF-S100 interactions may interfere with the sTNF recognition by the therapeutic anti-TNFs. Bioinformatics analysis reveals dysregulation of TNF and S100A11/A12/A13 in numerous disorders. Overall, we have shown a novel potential regulatory role of the extracellular forms of specific S100 proteins that may affect the efficacy of anti-TNF treatment in various diseases.

Body composition, physical activity, and quality of life in pediatric patients with inflammatory bowel disease on anti-TNF therapy—an observational follow-up study

BackgroundPoor outcome of inflammatory bowel disease (IBD) is associated with malnutrition. Our aim was to compare body composition (BC) and physical activity (PA) between patients with IBD and healthy controls, and to assess the changes in BC, PA and health related quality of life (HRQoL) in children with IBD during anti-TNF therapy.Methods32 children with IBD (21 with Crohn’s disease (CD), (age: 15.2 ± 2.6 years, 9 male) and 11 with ulcerative colitis (UC), (age: 16.4 ± 2.2 years, 5 male) participated in this prospective, observational follow up study conducted at Semmelweis University, Hungary. As control population, 307 children (age: 14.3 ± 2.1) (mean ± SD) were included. We assessed BC via bioelectric impedance, PA and HRQoL by questionnaires at initiation of anti-TNF therapy, and at two and six months later. The general linear model and Friedman test were applied to track changes in each variable.ResultsDuring follow-up, the fat-free mass Z score of children with CD increased significantly (-0.3 vs 0.1, p = 0.04), while the BC of patients with UC did not change. PA of CD patients was lower at baseline compared to healthy controls (1.1 vs. 2.4), but by the end of the follow up the difference disappeared.ConclusionsThe fat-free mass as well as PA of CD patients increased during the first six months of anti-TNF treatment. As malnutrition and inactivity affects children with IBD during an important physical and mental developmental period, encouraging them to engage in more physical activity, and monitoring nutritional status should be an important goal in patient care.

Cardiovascular risk assessment after anti-TNF treatment in patients with rheumatoid arthritis and ankylosing spondylitis with Strain Echocardiography

Cardiovascular risk assessment after anti-TNF treatment in patients with rheumatoid arthritis and ankylosing spondylitis with Strain Echocardiography

How sepsis parallels and differs from COVID-19.

How sepsis parallels and differs from COVID-19.

Prediction of response to anti-TNF treatment using laboratory biomarkers in patients with rheumatoid arthritis: a systematic review

ObjectivesIn this systematic review, we aim to identify laboratory biomarkers that predict response to tumour necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA).MethodsEMBASE, PubMed and Cochrane Library (CENTRAL)...

Real-World Evidence Comparing Vedolizumab and Ustekinumab in Antitumor Necrosis Factor-Experienced Patients With Crohn's Disease.

Many patients with Crohn's disease (CD) lose response or become intolerant to antitumor necrosis factor (TNF) therapy and subsequently switch out of class. We compared the effectiveness and safety of ustekinumab to vedolizumab in a large, geographically diverse US population of TNF-experienced patients with CD. We conducted a retrospective cohort study using longitudinal claims data from a large US insurer (Anthem, Inc.). We identified patients with CD initiating vedolizumab or ustekinumab with anti-TNF treatment in the prior 6 months. Our primary outcome was treatment persistence for >52 weeks. Secondary outcomes included (i) all-cause hospitalization, (ii) hospitalization for CD with surgery, (iii) hospitalization for CD without surgery, and (iv) hospitalization for infection. Propensity score fine stratification was used to control for demographic and baseline clinical characteristics and prior treatments. Among 885 new users of ustekinumab and 490 new users of vedolizumab, we observed no difference in treatment persistence (adjusted risk ratio 1.09 [95% confidence interval 0.95-1.25]). Ustekinumab was associated with a lower rate of all-cause hospitalization (adjusted hazard ratio 0.73 [0.59-0.91]), nonsurgical CD hospitalization (adjusted hazard ratio 0.58 [0.40-0.83]), and hospitalization for infection (adjusted hazard ratio 0.56 [0.34-0.92]). This real-world comparative effectiveness study of anti-TNF-experienced patients with CD initiating vedolizumab or ustekinumab showed similar treatment persistence rates beyond 52 weeks, although secondary outcomes such as all-cause hospitalizations, nonsurgical CD hospitalizations, and hospitalizations for infection favored ustekinumab initiation. We, therefore, advocate for individualized decision making in this medically refractory population, considering patient preference and other factors such as cost and route of administration.

Takayasu’s Arteritis Associated with Crohn’s Disease and Autoimmune Thyroiditis: An Unusual Association with Diagnostic and Therapeutic Difficulties

The coexistence of Crohn's disease (CD) and Takayasu's disease (TD) does not seem to be accidental and does not seem to modify the natural course of the 2 pathologies. The granulomatous character of the inflammatory infiltrate of the vascular wall appears to be the result of the pro-inflammatory effect of several cytokines, such as TNF and the IL-6, -8, -12 and -18 common to both entities. The literature reports more than 40 cases of Takayasu's disease associated with Crohn's disease. However, the association of these two pathologies with autoimmune thyroiditis has never been described before in the literature. In a case hospitalized in the gastroenterology department of the Mohammed VI University Hospital in Marrakech, of a woman with autoimmune thyroiditis treated by total thyroidectomy and hormone replacement therapy, Crohn's disease and Takayasu's disease for which she was treated by antiTNF treatment and the evolution was marked by a good clinical response.

Th2 Cytokines (Interleukin-5 and -9) Polymorphism Affects the Response to Anti-TNF Treatment in Polish Patients with Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is an inflammatory disease that belongs to the spondyloarthritis family. IL-5 and IL-9 belong to the group of Th2 cytokines of anti-inflammatory nature. Polymorphisms in their coding genes have been so far associated with various inflammatory diseases, but there are no reports regarding their involvement in AS pathogenesis to date. The purpose of the study was to investigate relationships between IL5 and IL9 genetic variants with AS susceptibility, clinical parameters as well as response to therapy with TNF inhibitors. In total 170 patients receiving anti-TNF therapy and 218 healthy controls were enrolled in the study. The genotyping of IL5 rs2069812 (A > G) and IL9 rs2069885 (G > A) single nucleotide polymorphisms was performed using the Real-Time PCR method based on LightSNiP kits assays. The present study demonstrated significant relationships between IL5 rs2069812 and IL9 rs2069885 polymorphisms and response to anti-TNF therapy. Presence of the IL5 rs2069812 A allele in patients positively correlated with better response to treatment (p = 0.022). With regard to IL9 rs2069885, patients carrying the A allele displayed better outcomes in anti-TNF therapy (p = 0.046). In addition, IL5 rs2069812 A and IL9 rs2069885 A alleles were associated with lower CRP and VAS values. The obtained results may indicate a significant role for IL-5 and IL-9 in the course of AS and response to anti-TNF therapy.

Systemic and T cell-associated responses to SARS-CoV-2 immunisation in gut inflammation (STAR SIGN study): effects of biologics on vaccination efficacy of the third dose of mRNA vaccines against SARS-CoV-2.

Immunosuppressed patients with inflammatory bowel disease (IBD) experience increased risk of vaccine-preventable diseases such as COVID-19. To assess humoral and cellular immune responses following SARS-CoV-2 booster vaccination in immunosuppressed IBD patients and healthy controls. In this prospective, multicentre, case-control study, 139 IBD patients treated with biologics and 110 healthy controls were recruited. Serum anti-SARS-CoV-2 spike IgG concentrations were measured 2-16 weeks after receiving a third mRNA vaccine dose. The primary outcome was to determine if humoral immune responses towards booster vaccines differ in IBD patients under anti-TNF versus non-anti-TNF therapy and healthy controls. Secondary outcomes were antibody decline, impact of previous infection and SARS-CoV-2-targeted T cell responses. Anti-TNF-treated IBD patients showed reduced anti-spike IgG concentrations (geometric mean 2357.4 BAU/ml [geometric SD 3.3]) when compared to non-anti-TNF-treated patients (5935.7 BAU/ml [3.9]; p< 0.0001) and healthy controls (5481.7 BAU/ml [2.4]; p< 0.0001), respectively. In multivariable modelling, prior infection (geometric mean ratio 2.00 [95% CI 1.34-2.90]) and vaccination with mRNA-1273 (1.53 [1.01-2.27]) increased antibody concentrations, while anti-TNF treatment (0.39 [0.28-0.54]) and prolonged time between vaccination and antibody measurement (0.72 [0.58-0.90]) decreased anti-SARS-CoV-2 spike antibodies. Antibody decline was comparable in IBD patients independent of anti-TNF treatment and antibody concentrations could not predict breakthrough infections. Cellular and humoral immune responses were uncoupled, and more anti-TNF-treated patients than healthy controls developed inadequate T cell responses (15/73 [20.5%] vs 2/100 [2.0%]; p= 0.00031). Anti-TNF-treated IBD patients have impaired humoral and cellular immunogenicity following SARS-CoV-2 booster vaccination. Fourth dose administration may be beneficial for these patients.

Risk of adverse outcomes in inflammatory bowel disease patients infected with SARS-CoV-2: a systematic review and meta-analysis.

BackgroundBetween people with and without inflammatory bowel disease (IBD), there was no statistically significant difference in the probability of contracting the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the risk of adverse outcomes in IBD patients after virus infection remains unclear.MethodsEligible studies conducted from January 1, 2020 to March 17, 2022 were obtained by searching PubMed, Embase, and Web of Science. Information was collected in tables from the included studies. Random-effects and fixed-effects models were used as measures for the pooled estimates. All data were estimated by R version 4.1.3.ResultsTwenty-four studies were included. The risk ratio (RR) of adverse outcomes in COVID-19 patients with IBD increased by 32% (RR 1.32; 95% CI 1.06–1.66) relative to COVID-19 patients without IBD. The RR of mortality was higher in COVID-19 patients with IBD from Europe (RR 1.72; 95% CI 1.11–2.67) than in those that were not from Europe (RR 1.00; 95% CI 0.79–1.26; χ2 = 4.67; P = 0.03). Patients with ulcerative colitis were at higher risk of adverse outcomes after SARS-CoV-2 infection than patients with Crohn’s disease patients (RR1.38; 95% CI 1.27–1.50). The IBD drugs treatment was associated with the risk of adverse outcomes, the pooled odds ratio (OR) of mesalazine (1.79; 95% CI 1.59–2.02), immunomodulators (1.30; 95% CI 1.10–1.53), and anti-TNF (0.47; 95% CI 0.41–0.53) were assessed.ConclusionCOVID-19 patients with IBD had an increased risk of adverse outcomes than those without IBD, whereas anti-TNF treatment might reduce the risk.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00384-022-04265-w.

Synovial Inflammatory Pathways Characterize Anti-TNF-Responsive Rheumatoid Arthritis Patients.

This study was undertaken to understand the mechanistic basis of response to anti-tumor necrosis factor (anti-TNF) therapies and to determine whether transcriptomic changes in the synovium are reflected in peripheral protein markers. Synovial tissue from 46 rheumatoid arthritis (RA) patients was profiled with RNA sequencing before and 12 weeks after treatment with anti-TNF therapies. Pathway and gene signature analyses were performed on RNA expression profiles of synovial biopsies to identify mechanisms that could discriminate among patients with a good response, a moderate response, or no response, according to the American College of Rheumatology (ACR)/EULAR response criteria. Serum proteins encoded by synovial genes that were differentially expressed between ACR/EULAR response groups were measured in the same patients. Gene signatures predicted which patients would have good responses, and pathway analysis identified elevated immune pathways, including chemokine signaling, Th1/Th2 cell differentiation, and Toll-like receptor signaling, uniquely in good responders. These inflammatory pathways were correspondingly down-modulated by anti-TNF therapy only in good responders. Based on cell signature analysis, lymphocyte, myeloid, and fibroblast cell populations were elevated in good responders relative to nonresponders, consistent with the increased inflammatory pathways. Cell signatures that decreased following anti-TNF treatment were predominately associated with lymphocytes, and fewer were associated with myeloid and fibroblast populations. Following anti-TNF treatment, and only in good responders, several peripheral inflammatory proteins decreased in a manner that was consistent with corresponding synovial gene changes. Collectively, these data suggest that RA patients with robust responses to anti-TNF therapies are characterized at baseline by immune pathway activation, which decreases following anti-TNF treatment. Understanding mechanisms that define patient responsiveness to anti-TNF treatment may assist in development of predictive markers of patient response and earlier treatment options.

The impact of smoking status on radiographic progression in patients with ankylosing spondylitis on anti-tumor necrosis factor treatment.

Ankylosing spondylitis (AS) is characterized by back pain which can lead to spinal ankylosis. Anti-tumor necrosis factor (TNF) dramatically alleviates symptoms, but spinal damage can still be progressive even during anti-TNF treatment. Smoking is a one of well-known risk factors for structural damage in AS. However, it has not been confirmed that smoking can affect radiographic progression even during anti-TNF treatment. To investigate factors associated with radiographic progression during anti-TNF treatment with a focus on smoking status which is known as one of poor prognostic factors for AS. We conducted a retrospective cohort study of AS patients who began the first-line anti-TNF treatment between 2001 and 2018 according to availability of smoking data. All enrolled patients were observed until the last visit, the first-line anti-TNF discontinuation, or December 2019. Radiographic damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). The mSASSS progression rate (units/year) was calculated using the baseline mSASSS, the final mSASSS during observation period, and the duration between them. Univariable and multivariable logistic regression analyses were performed to identify associated factors of mSASSS progression rate > 1 unit/year. Among 459 AS patients, 185 (40.3%) patients were never smokers, 62 (13.5%) were ex-smokers and 212 (46.2%) were current smokers at baseline. Ex- and current smokers had higher mSASSS progression rates than never smokers [never smoker 0.1 (0.0-0.7), ex-smoker 0.6 (0.0-1.5), and current smoker 0.6 (0.0-1.5) units/year, P < 0.001]. In the multivariable logistic analysis, current smoking [adjusted odds ratio (OR) 1.69, 95% CI 1.01-2.82, P = 0.047] and higher baseline mSASSS [adjusted OR 1.03, 95% CI 1.01-1.04, P < 0.001] were associated with a mSASSS progression rate > 1 unit/year. Current smoking is a modifiable risk factor for radiographic progression in patients with AS on anti-TNF treatment. Quitting smoking should be strongly recommended.

VDR Polymorphic Variants Are Related to Improvements in CRP and Disease Activity in Patients with Axial Spondyloarthritis That Undergo Anti-TNF Treatment.

Vitamin D deficiency is related with susceptibility or progression of various autoimmune diseases. The aim of the study was to assess potential relations between single nucleotide polymorphisms (SNPs) in the vitamin D receptor-coding gene (VDR): rs1544410 (BsmI), rs2228570 (FokI), rs731236 (TaqI), rs7975232 (ApaI), and disease activity in patients with axial spondyloarthritis (axSpA) undergoing anti-TNF therapy. The VDR rs731236 CT genotype was statistically more common among female patients (p = 0.027). An improvement of CRP equal to or higher than 50% after 3 months of anti-TNF therapy was observed for rs2228570 T allele (p = 0.002). After 6 months, CRP improvement equal to or higher than 75% was related to presence of the rs1544410 AA genotype (p = 0.027) and the rs731236 CC homozygotes (p = 0.047). Baseline BASDAI values were lower in individuals with the rs2228570 TT genotype (p = 0.036) and rs7975232 C allele (p = 0.029). After 6 months of treatment, lower BASDAI values were observed in AC heterozygotes (p = 0.005). The same AC genotype was more frequently detected in patients with remission (BASDAI ≤ 2) (p = 0.001) and in those achieving BASDAI improvement equal to or higher than 75% (p = 0.006). In conclusion, VDR SNPs were found to relate to CRP and BASDAI values at different time points of anti-TNF therapy.

Improved diagnosis of inflammatory bowel disease and prediction and monitoring of response to anti-TNF alpha treatment based on measurement of signal transduction pathway activity.

Objective: Ulcerative colitis (UC) and Crohn's disease (CD) are two subtypes of chronic inflammatory bowel disease (IBD). Differential diagnosis remains a challenge. Anti-TNFα treatment is an important treatment for IBD, yet resistance frequently occurs and cannot be predicted. Consequently, many patients receive ineffective therapy with potentially adverse effects. Novel assays are needed to improve diagnosis, and predict and monitor response to anti-TNF-α compounds. Design: Signal transduction pathway (STP) technology was used to quantify activity of STPs (androgen and estrogen receptor, PI3K, MAPK, TGFβ, Notch, Hedgehog, Wnt, NFκB, JAK-STAT1/2, and JAK-STAT3 pathways) in colon mucosa samples of CD and UC patients, based on transcriptome analysis. Previously described STP assay technology is based on computational inference of STP activity from mRNA levels of target genes of the STP transcription factor. Results: Results show that NFκB, JAK-STAT3, Wnt, MAPK, and androgen receptor pathways were abnormally active in CD and UC. Colon and ileum-localized CD differed with respect to STP activity, the JAK-STAT1/2 pathway being abnormally active in ileal CD. High activity of NFκB, JAK-STAT3, and TGFβ pathways was associated with resistance to anti-TNFα treatment in UC and colon-located CD, but not in ileal CD. Abnormal STP activity decreased with successful treatment. Conclusion: We believe that measuring mucosal STP activity provides clinically relevant information to improve differential diagnosis of IBD and prediction of resistance to anti-TNFα treatment in patients with colon-localized IBD, and provides new targets for treatment and overcoming anti-TNFα resistance.

55 Predictive factors of infection in patients with systemic autoimmune disease on biotherapy

IntroductionThe increasing use of biologics in chronic inflammatory diseases is accompanied by an increased risk of infectious complications. Our objective was to determine the predictive factors for the occurrence of infection in patients on biotherapy.MethodsWe conducted a single-center retrospective study in an internal medicine department over a period of 14-year [2009–2022], including the records of patients treated with a biologic agent presenting at least one infectious episode.ResultsDuring the study period, 20 patients among 50 treated with biologic agent had at least one infection episode. The patient mean age was 50.8 ± 12.1 [24–76] years and the male to female ratio was 1:2. The mean age at biotherapy first use was 43 ± 12.1 [17–68] years. Infections occurred after a mean duration of 12 months [0.5–36] after the initiation of biotherapy. Eleven patients were followed for chronic inflammatory bowel disease, three patients for ankylosing spondylitis, three patients for vasculitis, two patients for rheumatoid arthritis and one patient for systemic scleroderma. Only three patients were diabetic and two had chronic pulmonary disease. Thirteen patients (65%) were treated by TNFα inhibitors and 35% with anti CD20 (Rituximab). Among TNFα inhibitors, seven infections occurred in patient treated with infliximab (41%), six with adalimumab (35%) and four with etanercept (24%). At the time of infection, half of the patients were treated by corticosteroid with a median dose of 32 mg/d [5–60] and a median duration of 11 months [2–90], while 40% of the patients were on conventional immunosuppressive therapy. The infection was severe, requiring hospitalization in eight cases (40%). A statistically significant correlation was found between the occurrence of infection and a duration of anti-TNFα treatment <6 months (p = 0.003) and history of crohn's disease (p = 004). Age >50 years at the time of biotherapy introduction did not correlate with a higher risk of infection (p = 0.7)ConclusionScreening for infections in patient treated with biologic agents must be systematic, especially at the treatment initiation, in order to ensure better compliance and efficacy of the biotherapy.

Evaluation of anti-TNF treatment efficiency in children with immune-dependent diseases by means of testing the NF-κB activity in lymphocyte populations

Nuclear transcription factor B (NF-B) regulates innate and adaptive immunity functions and mediates inflammatory responses by activating proinflammatory cytokine gene transcription. TNF inhibitors block the NF-B signaling pathway, thus reducing inflammatory activity. The aim of the study was to evaluate the informativity of NF-kB transcription factor determination in the lymphocyte populations in children with inflammatory bowel disease (IBD) and psoriasis to assess the efficacy of anti-TNF therapy. We have examined 124 children with IBD and 55 children with psoriasis vulgaris administered maintenance anti-TNF therapy, and 30 healthy children. Stratification into the study groups was carried out according to PCDIA, PUCAI, PASI indices ( 10, remission). The number of cells with NF-B translocation was determined by flow cytometry with vusualization (Amnis ImageStreamX Mk II). Statistical evaluation was performed using Statistica 10.0 and SPSS 16.0. The highest number of cells with NF-B translocation was detected in B-lymphocytes and NK cells, thus being significantly higher than in T helper cells and cytotoxic T lymphocytes (p = 0.000). The percentage of cells with translocation of NF-B in populations of NK cells, T helper, cytotoxic T lymphocytes, Th17 lymphocytes, cytotoxic Th17 lymphocytes (Tc17) and Treg was increased in the patients at the acute disease stage against the comparison group. In the remission state, NF-B activity in lymphocyte populations was lower than in acute stage. In remission of psoriasis, NF-B activity in B lymphocytes, NK cells, and cytotoxic T lymphocytes was significantly lower than in comparison group. In IBD remission state, the NF-B activity was elevated only in T-helper cells. The level of NF-B translocation in the NK-cell population differed in children with IBD and psoriasis, both in acute phase (IBD, 46.2% (34-58); psoriasis, 36.5% (29-48), p = 0.041), and remission of disease (IBD, 25.4% (22-35); psoriasis, 19.1% (17-22), p = 0.000). ROC analysis of the data from exacerbation/remission states assessed as the NK cell numbers with NF-B translocation showed a good quality of the stratification model (AUC 0.8): The cut-off value in IBD was 41% (Se = 65.4; Sp = 89.1), and in psoriasis it was 23% (Se = 85.2; Sp = 94.7). The informativity of NF-B translocation level in lymphocyte populations in children with IBD and psoriasis was shown to correlate with efficacy of anti-TNF therapy. Exacerbation the disease with decreased therapeutic response is characterized by NF-B activation in lymphocyte populations in the children with IBD and psoriasis.

S983 Baseline Demographics and Disease Characteristics of Patients With Ulcerative Colitis Who Responded to Vedolizumab at Week 6

S983 Baseline Demographics and Disease Characteristics of Patients With Ulcerative Colitis Who Responded to Vedolizumab at Week 6