Anti-tumor Necrosis Factor Alpha Treatment Research Articles

Evaluation of adverse clinical outcomes in patients with inflammatory bowel disease receiving different sequences of first- and second-line biologic treatments: findings from ROTARY

BackgroundPatients with inflammatory bowel disease (IBD) are at risk of developing dysplasia and, subsequently, colorectal cancer (CRC) owing to chronic inflammation. Patients may also experience other severe disease complications, such as hospitalization and surgery. Several biologics are available for the treatment of patients with IBD and some patients require multiple lines of treatment owing to loss of response or tolerability to their prescribed biologic. Previous studies suggest that the choice of initial biologic treatment may impact the outcomes of later treatment lines. In this study, we assessed adverse clinical outcomes in patients with Crohn’s disease (CD) or ulcerative colitis (UC) who received different biologic treatment sequences.MethodsROTARY part B was a retrospective cohort study using the Optum® Clinical Database that evaluated the incidences of IBD-related hospitalization, IBD-related surgery, dysplasia, CRC, and infections in patients with CD or UC who received two biologics successively. First-line biologics included adalimumab, infliximab, ustekinumab (CD only), and vedolizumab; second-line biologics included infliximab and adalimumab.ResultsIn patients with CD, the treatment sequence of ustekinumab to infliximab was associated with the highest overall incidences of hospitalization (51.9%), surgery (40.7%), CRC (3.7%), and infection (37.0%). Vedolizumab followed by an anti-tumor necrosis factor alpha (anti-TNFα) treatment was associated with a significantly lower risk of experiencing an adverse medical event (hospitalization, surgery, or infection) than two successive anti-TNFα treatments (odds ratio, 1.526; 95% confidence interval, 1.004–2.320; P < 0.05). In patients with UC, the treatment sequence of vedolizumab to adalimumab resulted in the lowest overall incidence of adverse outcomes (20.3%, 6.3%, 0.0%, 6.3%, and 4.7% for hospitalization, surgery, CRC, dysplasia, and infection, respectively).ConclusionsWe describe differences in adverse clinical outcomes associated with sequencing of biologics in patients with CD or UC and demonstrate favorable results in patients who received vedolizumab as a first-line biologic. These results provide potential guidance to clinicians choosing sequences of biologic treatments in patients with IBD.

Impact of Anti-Tumor Necrosis Factor Alpha Treatment on Lipid Profile in Patients with Rheumatoid Arthritis

Impact of Anti-Tumor Necrosis Factor Alpha Treatment on Lipid Profile in Patients with Rheumatoid Arthritis

Long-term efficacy, safety, and cumulative retention rate of antitumor necrosis factor-alpha treatment for patients with Behcet's uveitis: A systematic review and meta-analysis.

This study aims to evaluate the long-term efficacy, safety, and cumulative retention rate of antitumor necrosis factor-alpha (anti-TNF-α) therapy for patients with Behcet's uveitis (BU) using meta-analysis. We searched the Web of Science and PubMed databases for eligible studies up to December 1, 2022. The quality of each identified study was assessed using the Joanna Briggs Institute's case series literature quality assessment tool. Statistical analysis was conducted using Stata 16.0 software with a random-effects model. Twelve studies comprising 1156 patients with BU were included in our analysis. We found that 85.0% of patients achieved ocular inflammation remission after receiving anti-TNF-α treatment, with a 95% confidence interval (CI) ranging from 78.7% to 90.5%. Additionally, 77.4% (95% CI: 57.5%-92.5%) experienced an improvement in visual acuity (VA). Moreover, the pooled dose reduction of glucocorticoids (GCs) was 11.08 mg (95% CI: -13.34 mg to -8.83 mg). Throughout the follow-up period, the cumulative retention rate of the medication was 67.3% (95% CI: 53.7%-79.6%). Serious adverse events occurred in 5.8% (95% CI: 3.1%-8.9%) of cases, with the three most common types being severe infusion or injection reactions (2.7%; 95% CI: 0.8%-5.4%), tuberculosis (1.3%; 95% CI: 0.0%-3.9%), and bacterial pneumonia (1.3%; 95% CI: 0.1%-3.4%). Subgroup analysis revealed that ocular inflammation remission rates were 89.3% (95% CI: 81.2%-95.5%) for adalimumab treatment and 83.7% (95% CI: 75.3%-90.8%) for infliximab treatment. The drug retention rate after adalimumab therapy was 70.3% (95% CI: 62.0%-78.0%) compared to 66.4% (95% CI: 48.6%-82.2%) for infliximab treatment. Furthermore, the incidence of severe infusion or injection reactions was 2.2% (95% CI: 0.1%-5.8%) following adalimumab treatment and 3.5% (95% CI: 0.7%-7.7%) following infliximab treatment. Anti-TNF-α therapy represents an effective treatment for BU patients with favorable safety profile and high drug retention rate and a potential advantage of adalimumab over infliximab in terms of ocular inflammation remission, drug retention, and the incidence of severe infusion or injection reactions.

P731 Relapse rate following withdrawal of anti-TNF therapy in patients with inflammatory bowel disease: A single-center experience

Abstract Background Discontinuation of anti–tumor necrosis factor alpha treatment (anti-TNFα) in patients with inflammatory bowel disease (IBD) poses a significant risk for relapse. The aim of this study is to analyze relapse rates and to possibly identify factors associated with relapse in IBD patients after treatment cessation with anti-TNFα. Methods This is a prospective study conducted at University Clinic of Gastroenterology in Albania from 2019-2022. IBD patients who discontinued biologic therapy with infliximab (IFX) or adalimumab (ADA) were included. All the patients discontinued therapy due to reimbursement issues. Demographic, clinical,laboratory and endoscopic data were collected for each patient. Relapse rates and predictors for relapse were studied using survival and Cox regression analysis. Results A total of 52 IBD patients, mean age 50.8±14.7 years (46 UC and 6 CD), 25(48%) males, were included in the study. Mean follow-up was 29 months. 47.4% were treated with ADA and 51.5 % with IFX. The mean period of biologic therapy was 33.3 months for all patients. Upon treatment cessation, 55.8% of patients were in complete clinical remission, and 30.8% were in partial clinical remission. Cumulative relapse rates at 6, 12, 24 and 36 months were 23.9%, 39.1%, 44.2% and 69.7% respectively for all UC patients while 66.7% of CD patients relapsed within 6 months. The mean time to relapse was 13 months for UC and 5 months for CD patients. Among all IBD patients in complete clinical remission at the time of treatment discontinuation, the cumulative relapse rates at 6, 12, 24 and 36 months, were: 6.9%, 24.8%, 57.7%, and 58% respectively. Significantly higher cumulative relapse rates were found in patients with partial remission, the at the same time points: 37.5%, 50%, 75%, and 81.2% respectively (p=0.01). Multivariable Cox analysis revealed that the only factor associated with lower risk of relapse was mucosal healing (vs nonmucosal healing: HR, 0.322; 95% CI, 1.26 to 6.677; p=0.012). Conclusion The majority of IBD patients relapsed within 3 years after anti TNFα discontinuation, Mucosal healing was the only factor associated with a lower risk of relapse. These results emphasise the crucial role of mucosal healing in guiding treatment decisions for IBD patients.

P922 A multicenter retrospective real-world study to determine the optimal cases of vedolizumab-treated UC patients

Abstract Background Vedolizumab (VDZ) is a gut-selective monoclonal antibody approved for ulcerative colitis (UC). This real-world study aimed to evaluate the effectiveness of VDZ in the treatment of UC, with the goal of further treatment optimization. Methods In this multicenter, retrospective, observational chart review, 370 patients with UC who received at least one dose of VDZ in clinical practice at 16 tertiary hospitals in Japan were enrolled. Comprehensive analyses of predictors of 2- and 54-week remission, drug persistence, and the development of loss of response were performed. Results Lower partial Mayo scores and lower Mayo endoscopic subscores were significantly associated with 2-week remission in the multivariate analysis. More 2-week remitters achieved clinical remission at Week 52 than non-2-week remitters. Clinical remission rates were significantly higher in biologic-naïve than in biologic-non-naïve patients across Weeks 2 to 54. Higher clinical remission rates at Week 54 were significantly associated with lower baseline disease severity and no prior anti-tumor necrosis factor alpha (anti- TNFα) treatment. Among patients with prior anti-TNFα treatment, longer duration of anti-TNFα treatment was associated with higher clinical remission rates at Week 54 (28.1%, 32.7%, and 60.0% for ≤3 months, &amp;gt;3 to &amp;lt;12 months, and ≥12 months, respectively, p=0.001 between groups). In addition, clinical remission rate at Week 54 was higher in patients who had loss of response to anti-TNFα treatment than in those who had primary nonresponse (54.4% vs 24.6%; p=0.001). The 54-week persistence rate was 64.5%. Concomitant use of tacrolimus (OR 2.76, 95% CI 1.00, 7.62, p=0.05) and shorter disease duration (median:7.8 years), (OR 0.33, 95% CI 0.13, 0.82 for ≥7.8 years vs &amp;lt;7.8 years p=0.017) were associated with loss of response to VDZ in the multivariate analysis, but prior use of anti- TNFα treatment was not. Conclusion This retrospective study confirms favorable outcomes with VDZ in patients without prior exposure to anti-TNFα treatment. However, among patients with history of anti-TNFα- exposure, better outcomes were observed among those who experienced loss of response than those with primary nonresponse, as well as those who had a longer duration of anti-TNFα treatment.

Dose Escalation of Biologics in Biologic-Naïve Patients With Ulcerative Colitis: Outcomes From the ODESSA-UC Study.

Dose escalation of biologics may regain treatment response in patients with ulcerative colitis (UC). However, dose escalation rates and associated outcomes and costs are not well characterized in biologic-naïve patients receiving antitumor necrosis factor-alpha (anti-TNF-α) treatments, such as infliximab or adalimumab or vedolizumab. ODESSA-UC, a retrospective cohort study investigating dose escalation in patients with UC who had received first-line biologics, used data from IBM MarketScan databases. Adults with UC and ≥1 claim for an index drug (adalimumab, infliximab, or vedolizumab) were eligible. A Cox proportional hazards model was used to evaluate the adjusted rate of dose escalation. Logistic regression was used to evaluate the odds of experiencing adverse outcomes (corticosteroid use, infection, sepsis, or inflammatory bowel disease-related hospitalization) and incurring index drug costs. A year after the start of maintenance, a lower proportion of patients experienced dose escalation with vedolizumab (22.3%) than adalimumab (43.0%). The dose escalation risk was significantly higher for infliximab (hazard ratio [HR], 1.894; 95% confidence interval [CI], 1.486-2.413) and adalimumab (HR, 2.120; 95% CI, 1.680-2.675) than for vedolizumab. The odds of experiencing an adverse outcome after dose escalation were higher for anti-TNF-α treatments than for vedolizumab (odds ratio, 2.052; 95% CI, 1.200-3.507). Index drug costs after dose escalation were lowest for vedolizumab. Patients with UC receiving vedolizumab had a lower risk of dose escalation and lower subsequent costs than patients receiving anti-TNF-α treatments. Our study demonstrates the possible clinical and economic implications of dose escalation.

Comparison of surgery rates in biologic-naïve patients with Crohn’s disease treated with vedolizumab or ustekinumab: findings from SOJOURN

BackgroundCrohn’s disease (CD) is a chronic inflammatory bowel disease characterized by relapsing and remitting inflammation that leads to progressive bowel damage. Despite advances in medical treatment for CD, many patients require surgical intervention. Most studies of surgery rates are from patients treated with anti-tumor necrosis factor alpha (anti-TNFα) treatments, with comparatively little data on the surgery rates of patients treated with vedolizumab and ustekinumab. SOJOURN aimed to estimate the hazard rate and incidence of the first CD-related surgery following initiation of treatment with vedolizumab or ustekinumab in biologic-naïve patients with CD.MethodsSOJOURN was a retrospective, observational cohort study examining administrative claims data from the Optum® Research Database between July 1, 2017 and March 31, 2020. Included participants were adults with a diagnosis of CD and a claim for vedolizumab or ustekinumab (defined as the index treatment) between January 1, 2018 and December 31, 2019, with no claims for a biologic in the 6 months before initiation of this treatment. The variable follow-up started on the day after the index date and continued until whichever came first of discontinuation of the index treatment, surgery event, switching of the index treatment, initiation of combination biologic treatment, disenrollment, or March 31, 2020. The time to the first CD-related surgery on biologic treatment was estimated by Kaplan–Meier analysis. The hazard ratio and incidence rate ratio of CD-related surgery for each treatment cohort was compared using a Cox proportional hazards model and a Poisson regression model, respectively.ResultsOf the 1,122 included patients, 578 received vedolizumab and 544 received ustekinumab. After 1 year of the variable follow-up, 7.7% of patients receiving vedolizumab and 11.6% of patients receiving ustekinumab had undergone a CD-related surgery. Vedolizumab was associated with a 34.2% lower hazard rate of surgery (hazard ratio 0.658, 95% confidence interval [CI] 0.436–0.994, p = 0.047) and a 34.5% lower incidence of surgery (rate ratio 0.655, 95% CI 0.434–0.988, p = 0.044) than ustekinumab.ConclusionsThis real-world analysis of biologic-naïve patients with CD suggests that vedolizumab is associated with greater effectiveness in reducing the rate of CD-related surgery than ustekinumab.

Anti-tumor necrosis factor alpha treatment does not influence serum levels of the markers associated with radiographic progression in ankylosing spondylitis.

The study aimed to determine the levels of change of the markers related to radiographic progression, such as Dickkopf-1 (DKK-1), sclerostin (SOST), bone morphogenetic protein (BMP)-2 and -4, and interleukin (IL)-17 and -23, in ankylosing spondyloarthritis (AS) during anti-tumor necrosis factor alpha (TNF-α) treatment. Fifty-three anti-TNF-α naïve AS patients (34 males, 19 females; median: 38 years; range, 20 to 52 years) refractory to conventional treatments meeting the modified New York criteria or Assessment of SpondyloArthritis International Society classification criteria were enrolled to this cross-sectional, controlled study between October 2015 and January 2017. Fifty healthy volunteers (35 males, 15 females; median: 36 years; range, 18 to 55 years) with similar age and sex characteristics were recruited. Serum DKK-1, BMP-2, BMP-4, SOST, IL-17, and IL-23 levels were measured in both groups. The serum levels of the markers were measured again after about two years (mean follow-up duration of 21.7±6.4 months) in AS patients who started anti-TNF-α treatment. Demographic, clinical characteristics, and laboratory parameters were recorded. The disease activity at the time of inclusion was assessed through the Bath Ankylosing Spondylitis Disease Activity Index. Serum DKK-1, SOST, IL-17, and IL-23 levels in the AS group before anti-TNF-a treatment were significantly higher compared to the control group (p<0.01 for DKK-1, p<0.001 for others). There was no difference regarding serum BMP-4 levels, whereas BMP-2 levels were significantly higher in the control group (p<0.01). Forty (75.47%) AS patients had serum marker levels measured after anti-TNF-α treatment. No significant change was observed in the serum levels of these 40 patients measured 21.7±6.4 months after the initiation of anti-TNF-α treatment (p>0.05 for all). In AS patients, there was no change in DKK-1/SOST, BMP, and IL-17/23 cascade with anti-TNF-α treatment. This finding may suggest that these pathways act independently of each other, and their local effects are not influenced by systemic inflammation.

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

Identified potential biomarkers may predict primary nonresponse to infliximab in patients with ulcerative colitis

Primary nonresponse to infliximab in patients with ulcerative colitis (UC) is common. However, there are currently no effective biomarkers for this prediction. This study aimed to identify potential predictors for precision anti-tumor necrosis factor-alpha treatment in patients with UC. Four GPL570 datasets (GSE14580, GSE12251, GSE23597, and GSE16879) were included in this study. Sixty-nine differentially expressed genes (DEGs) were identified, while 67 were up-regulated and two were down-regulated by comparing the gene expression in response samples with the nonresponse samples. Gene Ontology analysis showed that DEGs were mostly enriched in neutrophil-mediated immunity, neutrophil activation, neutrophil activation involved in the immune response, neutrophil degranulation, and leukocyte migration. Kyoto Encyclopaedia of Genes and Genomes analysis indicated that these DEGs were mostly enriched in cytokine-cytokine receptor interactions and interleukin (IL)-17 signalling pathways. After protein-protein interaction network analysis, verification by test set, and confirmation of clinical UC samples, S100 calcium-binding protein A8 (S100A8), S100A9, triggering receptor expressed on myeloid cells 1 (TREM1), toll-like receptor 2 (TLR2), IL1B, and formyl peptide receptor 1 (FPR1) were identified as the hub genes. We found that the immune cell composition in the intestinal tissues of UC patients with primary nonresponse included naïve CD4+ T cells, memory resting CD4+ T cells, resting natural killer cells, resting dendritic cells, activating dendritic cells, eosinophils, and neutrophils. Among these, neutrophils showed the most significant differences. In addition, all six potential predictors were significantly associated with the neutrophil count. Our study identified six potential biomarkers, namely S100A8, S100A9, TREM1, TLR2, IL1B, and FPR1, and one type of immune cell, neutrophils, between UC patients with response and primary nonresponse to infliximab. We speculated that changes in the expression of these six potential biomarkers combined with changes in the activity or local quantity of neutrophils might help predict primary nonresponse to infliximab in patients with UC.

Anti-tumor necrosis factor-alpha treatment in pediatric patients with pars planitis: a single-center experience from Turkey.

To evaluate the effectiveness and safety of anti-tumor necrosis factor-alpha (anti-TNF-alpha) treatment (Adalimumab [ADA]) combined with immunomodulatory agents (IMAs) in the treatment of pars planitis (PP). The patients with PP who were treated with anti-TNF-alpha agents for at least six months were qualified for the chart review. The outcome parameters were the steroid-free remission state, the best-corrected visual acuity (BCVA) and the central macular thickness (CMT) of the patients at the last visit. After a mean total follow-up time of 15.5 ± 5.8months (8-24months), all the cases were in steroid-free remission at the last visit. The mean BCVA increased, and the mean CMT decreased significantly at the last visit (p < 0.001, p < 0.001, respectively). ADA combined with IMAs offers effective and safe treatment modalities in the control of chronic intraocular inflammation in PP cases.

The Effects of TNF-α Inhibition on the Metabolism of Cartilage: Relationship between KS, HA, HAPLN1 and ADAMTS4, ADAMTS5, TOS and TGF-β1 Plasma Concentrations in Patients with Juvenile Idiopathic Arthritis.

We assessed the effect of 24-month anti-tumor necrosis factor alpha (TNF-α) treatment on the remodeling of the cartilage extracellular matrix (ECM) in patients with juvenile idiopathic arthritis (JIA). Methods: Quantitative evaluation of keratan sulfate (KS), hyaluronic acid (HA), hyaluronan and proteoglycan link protein 1 (HAPLN1), as potential biomarkers of joint dysfunction, and the levels of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 4 and 5, total oxidative status (TOS) and transforming growth factor (TGF-β1) was performed (using immunoenzymatic methods) in blood obtained from patients before and after 24 months of etanercept (ETA) treatment. Results: When compared to the controls, KS, HA and HAPLN1 levels were significantly higher in patients with an aggressive course of JIA qualified for ETA treatment. An anti-cytokine therapy leading to clinical improvement promotes the normalization only of the HA level. Proteolytic and pro-oxidative factors, present in high concentrations in patients before the treatment, correlated with HAPLN1, but not with KS and HA levels. In these patients, negative correlations were found between the levels of TGF-β1 and KS, HA and HAPLN1. Conclusion: The anti-TNF-α therapy used in patients with JIA has a beneficial effect on ECM cartilage metabolism, but it does not completely regenerate it. The changes in the plasma HA level during the anti-cytokine therapy suggest its potential diagnostic utility in monitoring of disease activity and may be used to assess the efficacy of ETA treatment.

P382 High anti-tumor necrosis factor alpha treatment trough concentrations are not associated with higher rate of adverse events in pediatric patients with inflammatory bowel disease

Abstract Background Anti-tumor necrosis factor alpha (anti-TNFα) therapy is commonly used to treat refractory pediatric inflammatory bowel disease (IBD). Prolonged use of anti-TNFα therapy has been linked to a number of adverse events. We aimed to assess the relationship between serum trough concentrations (TC) of anti-TNFα and adverse events rate among patients with pediatric IBD. Methods The medical records of 135 pediatric patients with IBD who were treated with anti-TNFα agents from 2015 to 2020 and had sequential monitoring of TC were reviewed retrospectively for the presence of adverse events (infusion reactions, infections, acute cutaneous reactions, psoriatiform rashes, elevated transaminases and others). The association between demographic or disease related variables and adverse events were analyzed using multivariate analysis. Results Out of 135 patients, [59 (43.7%) female, mean age at diagnosis 12.9 (±3)years, 111 (82.2%) Crohn’s disease] who had 1645 measurements of TC [1037(63%) infliximab, range 0-46 µgr/ml] during a median follow-up period of 1.7 years (1.1-2.7), we recorded 120 adverse events in 42 patients (31%). When analyzing TC as continuous measure or as a categorical measure (&amp;gt; or &amp;lt;10 µgr/ml) there were not associated with a higher rate of adverse events (p=0.9).Patients who reported non-infusion related adverse events were younger at the time of diagnosis (mean age 11.4±3.9 vs.13.3±2.8years) than those without adverse effect (p=0.029). There was no statistically significant correlation between other variables (gender, disease type, Paris classification, extra-intestinal manifestation, perianal disease, and the pediatric disease activity index) and the occurrence of adverse events. Conclusion Based on our cohort, higher TCs were not associated with higher rate of anti-TNF related adverse events whereas younger age at diagnosis increased the risk for such events. The study protocol was approved by the local Internal Review Board at the Rabin/Schneider Medical Center (RMC0320-10).

Clinical course of central nervous system demyelinating neurological adverse events associated with anti-TNF therapy.

Previous studies have reported an association between anti-tumor necrosis factor alpha (anti-TNFα) treatment and central nervous system (CNS) events. We described eight patients presenting with demyelinating CNS events while on treatment with anti-TNFα for autoimmune diseases and followed up for a medium period of 4years. Four patients presented with isolated demyelinating events, three patients fulfilled the criteria for multiple sclerosis (MS), and one patient showed worsening of pre-existing MS after anti-TNF therapy initiation. All patients except one, showed a good medium-term prognosis. Our observation supports an association between anti-TNFα treatment and demyelinating events and suggests that a prompt discontinuation of the drug may lead to a favorable demyelinating disease outcome.

Real-world clinical effectiveness and safety of vedolizumab and anti-tumor necrosis factor alpha treatment in ulcerative colitis and Crohn\u2019s disease patients: a German retrospective chart review

BackgroundReal-world comparisons of biologic treatment outcomes for ulcerative colitis (UC) or Crohn’s disease (CD) patients are limited. We sought to evaluate the real-world effectiveness of vedolizumab (VDZ) and anti-tumor necrosis factor alpha (anti-TNFα) in UC and CD patients in Germany.MethodsA retrospective chart review (15 sites) investigated UC and CD patients who were biologic-treatment naïve (biologic-naïve) or had received no more than one prior anti-TNFα before initiating treatment with VDZ or anti-TNFα between 15 July 2014 and 20 October 2015. Kaplan-Meier analyses assessed time to first chart-documented clinical remission (CR) and symptom resolution (UC: rectal bleeding [RB], stool frequency [SF]; CD: abdominal pain [AP], liquid stools [LS]) and outcome duration.ResultsA total of 133 UC (76 VDZ; 57 anti-TNFα) and 174 CD (69 VDZ; 105 anti-TNFα) patients were included. By Week 26, estimated cumulative rates of patients achieving CR or symptom resolution with VDZ vs anti-TNFα treatment were for UC: CR, 53.7% vs 31.7%; RB, 66.8% vs 55.8%; and SF, 59.8% vs 50.7%, respectively; and for CD: CR, 14.4% vs 32.8%; AP, 62.5% vs 56.0%; and LS, 29.9% vs 50.3%, respectively. Outcomes were sustained similarly between treatments, except RB (VDZ vs anti-TNFα: median 38.1 vs 15.1 weeks, P = 0.03). Treatment-related adverse events occurred in 5.3% vs 7.0% (UC) and 8.7% vs 19.0% (CD) of VDZ vs anti-TNFα patients, respectively.ConclusionsAlthough there were differences in CR, symptom resolution, and safety profiles, real-world data support both VDZ and anti-TNFα as effective treatment options in UC and CD.

Current Diagnostic and Therapeutic Approaches to Cytomegalovirus Infections in Ulcerative Colitis Patients Based on Clinical and Basic Research Data.

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus (the human herpesvirus 5) and an opportunistic pathogen that primarily infects HIV-positive and other immuno-compromised patients. Retrospective studies in the field of inflammatory bowel disease (IBD) have suggested a relationship between a concomitant colonic HCMV infection and poor outcomes in patients with an ulcerative colitis (UC) due to the presence of HCMV in surgical specimens of patients with a toxic megacolon or a steroid-resistant UC. Therefore, gastroenterologists have focused on the contribution of HCMV infections in the exacerbation of UC. Numerous studies have addressed the benefits of treating colonic HCMV reactivation in UC using an antiviral treatment. However, its clinical relevance remains uncertain as only a few prospective studies have assessed the direct relationship between clinical outcomes and the viral load of HCMV in colonic tissues. HCMV reactivation can be triggered by inflammation according to fundamental research studies. Thus, optimal control of intestinal inflammation is essential for preventing an HCMV reactivation in the intestinal mucosa. Indeed, several reports have indicated the effectiveness of an anti-tumor necrosis factor-alpha (TNFα) treatment in patients with an active UC and concomitant HCMV infections. In this review, we describe the mechanism of HCMV reactivation in UC cases and discuss the current issues regarding diagnosis and treatment of HCMV infections in UC patients.

Levels of Intestinal Inflammation and Fibrosis in Resection Specimens after Preoperative Anti-Tumor Necrosis Factor Alpha Treatment in Patients with Crohn's Disease: A Comparative Pilot Study.

Background Strictures are a common complication in Crohn's disease (CD), found in more than 50% of patients. They are characterized by the excessive deposition of extracellular proteins in the tissue as a result of the chronic inflammatory process. The effect of anti-tumor necrosis factor alpha (TNF-α) therapy on the development of fibrosis is not yet fully understood. Aim To investigate whether the degree of intestinal inflammation and fibrosis is correlated with preoperative anti-TNF-α) therapy on the development of fibrosis is not yet fully understood. Methods This unblinded, prospective, single tertiary center, pilot cohort study included all adult patients with CD who underwent elective, laparoscopic, or open intestinal resection. Preoperative investigations included measurement of blood TNF-α) therapy on the development of fibrosis is not yet fully understood. Results Histopathological specimens from 10 patients with CD who underwent ileocecal or ileocolic resections were retrieved. Four of those patients were on anti-TNF-α) therapy on the development of fibrosis is not yet fully understood. α) therapy on the development of fibrosis is not yet fully understood. α) therapy on the development of fibrosis is not yet fully understood. p=0.01). Anti-TNF-α) therapy on the development of fibrosis is not yet fully understood. α) therapy on the development of fibrosis is not yet fully understood. α) therapy on the development of fibrosis is not yet fully understood. Conclusions Patients who underwent preoperative anti-TNF-α treatment had a higher fibrosis score than controls.α) therapy on the development of fibrosis is not yet fully understood.

Factors that influence rheumatologists\u2019 anti-tumor necrosis factor alpha prescribing decisions: a qualitative study

BackgroundTreatment decisions for any disease are usually informed by reference to published clinical guidelines or recommendations. These recommendations can be developed to improve the relative cost-effectiveness of health care and to reduce regional variation in clinical practice. Anti-tumor necrosis factor alpha (anti-TNF) treatments are prescribed for people with rheumatoid arthritis according to specific recommendations by the National Institute for Health and Care Excellence in England. Evidence of regional variation in clinical practice for rheumatoid arthritis may indicate that different factors have an influence on routine prescribing decisions. The aim of this study was to understand the factors that influence rheumatologists’ decisions when prescribing anti-TNF treatments for people with rheumatoid arthritis in England.MethodsSemi-structured one-to-one telephone interviews were performed with senior rheumatologists in different regions across England. The interview schedule addressed recommendations by the National Institute for Health and Care Excellence, prescribing behavior, and perceptions of anti-TNF treatments. Interviews were recorded digitally, transcribed verbatim, and anonymized. Data were analyzed by thematic framework analysis that comprised six stages (familiarization; coding; developing the framework; applying the framework; generating the matrix; interpretation).ResultsEleven rheumatologists (regional distribution - north 36%; midlands: 36%; south: 27%) participated (response rate: 24% of the sampling frame). The mean duration of the interviews was thirty minutes (range: 16 to 56 min). Thirteen factors that influenced anti-TNF prescribing decisions were categorized by three nested primary themes; specific influences were defined as subthemes: (i) External Environment Influences (National Institute for Health and Care Excellence Recommendations; Clinical Commissioning Groups; Cost Pressures; Published Clinical Evidence; Colleagues in Different Hospitals; Pharmaceutical Industry); (ii) Internal Hospital Influences (Systems to Promote Compliance with Clinical Recommendations; Internal Treatment Pathways; Hospital Culture); (iii) Individual-level Influences (Patient Influence; Clinical Autonomy; Consultant Experience; Perception of Disease Activity Score-28 (DAS28) Outcome).ConclusionsFactors that influenced anti-TNF prescribing decisions were multifaceted, seemed to vary by region, and may facilitate divergence from published clinical recommendations. Strategic behavior appeared to illustrate a conflict between uniform treatment recommendations and clinical autonomy. These influences may contribute to understanding sources of regional variation in clinical practice for rheumatoid arthritis.

Serum levels of inhibitors of wingless / beta-catenin in patients with ankylosing spondylitis and the relationship with anti-tumour necrosis factor alpha treatments

Aim: The primary aim of the study was to compare the serum levels of Dickkopf-1 (DKK-1) and sclerostin in patients with ankylosing spondylitis (AS) and healthy controls. The secondary aim was to evaluate the effects of anti-tumor necrosis factor alpha (TNF-α) treatments on levels of DKK-1 and sclerostin. The last aim was to evaluate any relationship between DKK-1, sclerostin, and radiologic progression in AS. Material and Method: We included 70 patients with AS (35 anti-TNF-α treated, 35 anti-TNF-α naive) and 31 healthy controls in this study. Serum DKK-1, sclerostin, C reactive protein, and erythrocyte sedimentation rate (ESR) were assessed in patients and healthy controls. The Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI), and Bath Ankylosing Spondylitis Functional Index (BASFI) were calculated for the patients. Radiographs were scored according to the modified Stoke AS Spine Score (mSASSS) by an experienced radiologist who was blinded to the patients’ identity. Results: Patients with AS who were treated with anti-TNF-α agent had higher scores of BASMI and mSASSS compared with the anti-TNF-α naive patients. Serum levels of DKK-1 and sclerostin were significantly lower in patients with AS than in healthy controls. There was a negative correlation between DKK-1 levels with ASDAS and BASMI in patients with AS. There was no correlation between DKK-1 or sclerostin levels with mSASSS. There was a positive correlation between BASMI score with mSASSS in patients with AS. Conclusion: DKK-1 levels in patients with AS were negatively correlated with BASMI, on the other hand, BASMI had a strong positive correlation with mSASSS. Therefore, these findings suggest that lower DKK-1 levels in patients with AS may play a role in new bone formation.

Effects of a 15-month anti-TNF-\u03b1 treatment on plasma levels of glycosaminoglycans in women with rheumatoid arthritis

BackgroundIn this study, the effect of 15-month anti-tumor necrosis factor alpha (TNF-α) treatment on circulating levels of plasma sulfated glycosaminoglycans (GAGs) and the nonsulfated GAG hyaluronic acid (HA) in female rheumatoid arthritis (RA) patients was assessed.MethodsPlasma was obtained from healthy subjects and RA women treated with TNF-α antagonists (etanercept or adalimumab or certolizumab pegol) in combination with methotrexate. GAGs were isolated from plasma samples using ion exchange low-pressure liquid chromatography. Total sulfated GAGs were quantified using a hexuronic acid assay. Plasma levels of keratan sulfate (KS) and HA were measured using immunoassay kits.ResultsTotal sulfated GAGs and HA levels were higher in female RA patients before treatment in comparison to healthy subjects. KS levels did not differ between RA women and controls. Anti-TNF-α treatment resulted in normalization of plasma total GAG and HA levels in RA patients, without any effect on KS levels.ConclusionsOur results suggest that anti-TNF-α therapy has a beneficial effect on extracellular matrix remodeling in the course of RA.