Comparative Analysis of the 3-Year Persistence Rate with Second-Line Vedolizumab and Tumor Necrosis Factor-α Inhibitors in Patients with Inflammatory Bowel Disease Followed in Gastroenterology Practices in Germany

2020 ◽  
Vol 38 (6) ◽  
pp. 466-473
Author(s):  
Ulf Helwig ◽  
Fiona Braegger ◽  
Karel Kostev ◽  
Carsten Schmidt
Keyword(s):  
Tumor Necrosis ◽  
Matched Pair ◽  
Second Line ◽  
Matched Pair Analysis ◽  
Therapy Initiation ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Pair Analysis ◽  
Necrosis Factor

<b><i>Background:</i></b> Our goal was to investigate the 3-year persistence rates with second-line vedolizumab and tumor necrosis factor-α (TNF-α) inhibitors (i.e., adalimumab, golimumab, infliximab) in patients with inflammatory bowel disease (IBD) who were followed in gastroenterology practices in Germany. <b><i>Methods:</i></b> This study included patients aged ≥18 years who had received prescriptions for second-line biological drugs in Germany between 2014 and 2017 (<i>n</i> = 5,150) retrieved from the longitudinal prescription database. Vedolizumab users were matched to adalimumab, golimumab, and infliximab users based on age, sex, and index year. The primary outcome of the study was the rate of persistence with vedolizumab compared with the rate of persistence with adalimumab, golimumab, and infliximab within 3 years of second-line therapy initiation in IBD patients. Persistence was estimated as therapy time without discontinuation, with discontinuation being defined as at least 90 days without any prescription for the biological drug of interest. <b><i>Results:</i></b> After matching patients who had received vedolizumab with those who had received adalimumab, the rate of persistence after 3 therapy years was 30.3% for vedolizumab and 27.9% for adalimumab (log-rank <i>p</i> = 0.005). The corresponding figures were 27.8 and 20.8% in the vedolizumab-golimumab matched-pair analysis (log-rank <i>p</i> &#x3c; 0.001) and 29.5 and 25.2% in the vedolizumab-infliximab matched-pair analysis (log-rank <i>p</i> value = 0.008). Vedolizumab was associated with a significant 0.85-, 0.72-, and 0.86-fold decrease in the risk of discontinuation within 3 years of therapy initiation compared to adalimumab, golimumab, and infliximab, respectively. <b><i>Conclusions:</i></b> Treatment persistence was higher for vedolizumab than for TNF-α inhibitors up to 3 years after initiating second-line biological therapy.

scholarly journals Review: Local Tumor Necrosis Factor-α Inhibition in Inflammatory Bowel Disease

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 539
Author(s):  
Bahez Gareb ◽  
Antonius T. Otten ◽  
Henderik W. Frijlink ◽  
Gerard Dijkstra ◽  
Jos G. W. Kosterink
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Genetically Modified Organisms ◽  
Intestinal Inflammation ◽  
Systemic Exposure ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Necrosis Factor

Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterized by intestinal inflammation. Increased intestinal levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) are associated with disease activity and severity. Anti-TNF-α therapy is administered systemically and efficacious in the treatment of IBD. However, systemic exposure is associated with adverse events that may impede therapeutic treatment. Clinical studies show that the efficacy correlates with immunological effects localized in the gastrointestinal tract (GIT) as opposed to systemic effects. These data suggest that site-specific TNF-α inhibition in IBD may be efficacious with fewer expected side effects related to systemic exposure. We therefore reviewed the available literature that investigated the efficacy or feasibility of local TNF-α inhibition in IBD. A literature search was performed on PubMed with given search terms and strategy. Of 8739 hits, 48 citations were included in this review. These studies ranged from animal studies to randomized placebo-controlled clinical trials. In these studies, local anti-TNF-α therapy was achieved with antibodies, antisense oligonucleotides (ASO), small interfering RNA (siRNA), microRNA (miRNA) and genetically modified organisms. This narrative review summarizes and discusses these approaches in view of the clinical relevance of local TNF-α inhibition in IBD.

Effectiveness of tumor necrosis factor α inhibitors and their concentration and immunogenicity: features in various immune-mediated diseases

2021 ◽  
pp. 47-52
Author(s):  
T. Yu. Nuriakhmetova ◽  
I. Kh. Valeeva ◽  
Ya. O. Shevnina ◽  
N. A. Cheremina ◽  
E. V. Sukhorukova ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Certolizumab Pegol ◽  
Low Concentration ◽  
Immune Mediated ◽  
Tnf Α ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Necrosis Factor

Aim. To compare the concentration and immunogenicity of TNF-α inhibitors (TNFi) and their relationship with efficacy in patients with rheumatic diseases (RD) and inflammatory bowel diseases (IBD).Materials and methods. The study included 104 patients with RD (48.1%) and IBD (51.9%) who received infliximab (INF, 30.8%), adalimumab (ADA, 38.5%) and certolizumab pegol (CZP, 30.8%). We assessed the efficacy of the drug, trough concentration of TNFi and the level of antibodies. In 30 patients, the concentration of TNFi and the level of antibodies were assessed twice with an interval of 15 [13; 17] months.Results. TNF-α inhibitors were effective in 77 (74%) patients. In the group of IBD and RD, the incidence of inefficiency was 33.3% and 18.0%, the ineffectiveness of CZP was found only in IBD group (p = 0.024). A low concentration of TNFi was detected at the first visit in 29 (53.7%) patients with IBD and 24 (48.0%) with RD, at the second visit in 4 (36.4%) patients with IBD and 9 (47.4%) with RD. In all patients with RD who did not respond to IFN and CZP, the subtherapeutic concentration was determined (p = 0.047), in the IBD group – only in 64.3% cases (p > 0.050). At the first visit, antibodies to TNFi were found in 24 (23.1%) patients, at the second visit in 7 (23.3%) exclusively in the RD group (p = 0.019), in 5 of them repeatedly. The formation of Ab was associated with 27.8% of cases of escape of the effect of TNF-α in IBD and 22.2% of cases of ineffectiveness in RD (p > 0.050).Conclusions. The incidence of TNF-α efficacy did not differ between RD and IBD, CZP ineffectiveness was observed exclusively in patients with IBD. In patients with RD, a significant relationship was found between ineffectiveness and low concentration of TNFi. The frequency of Ab formation did not differ between the groups of diseases.

scholarly journals Tumor Necrosis Factor-α in Serum of Patients with Inflammatory Bowel Disease as Measured by a Highly Sensitive Immuno-PCR

2001 ◽  
Vol 47 (7) ◽  
pp. 1297-1301 ◽  
Author(s):  
Momoko Komatsu ◽  
Daisuke Kobayashi ◽  
Kaori Saito ◽  
Daisuke Furuya ◽  
Atsuhito Yagihashi ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Pcr Amplification ◽  
Median Serum ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Necrosis Factor

Abstract Background: The significance of serum concentrations of tumor necrosis factor-α (TNF-α) in the pathogenesis of inflammatory bowel disease (IBD) is uncertain. We measured TNF-α in serum from IBD patients by immuno-PCR to analyze the relationship between TNF-α and pathophysiologic state in IBD. Methods: Serum samples were collected from 54 healthy blood donors, 29 patients with ulcerative colitis (UC; 46 samples), and 7 patients with Crohn disease (CD; 8 samples). DNA label was generated by PCR amplification using biotinylated primer and was bound with streptavidin to biotinylated third antibody. TNF-α sandwiched by antibodies was detected by PCR amplification of the DNA label. Results: TNF-α could be measured in all samples. The median serum concentration in IBD patients overall was ∼390-fold higher than in healthy donors (median increase, 380-fold for UC, 640-fold for CD). The median serum TNF-α concentration was 1.7-fold higher in the active stage of UC than in the inactive stage (P &lt;0.05), and this difference could be detected in individual patients. Conclusions: Sensitive measurement of serum TNF-α could provide an important pathophysiologic marker for the presence and activity of IBD.

scholarly journals TNF Inhibitor-Induced Psoriasis: Proposed Algorithm for Treatment and Management

2018 ◽  
Vol 4 (2) ◽  
pp. 70-80 ◽  
Author(s):  
Sara Jiayang Li ◽  
Lourdes M. Perez-Chada ◽  
Joseph F. Merola
Keyword(s):  
Tumor Necrosis ◽  
Treatment Algorithm ◽  
Psoriatic Skin ◽  
Tnf Inhibitor ◽  
Novel Treatment ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Necrosis Factor

Tumor necrosis factor α (TNF-α)-targeted therapies have expanded the therapeutic options for patients with inflammatory bowel disease (IBD), rheumatoid arthritis (RA), psoriasis, and psoriatic arthritis (PsA) and have significantly improved patients’ quality of life. Paradoxically, anti-TNF-α agents may induce psoriatic eruptions or worsen preexisting psoriatic skin disease. Currently, there is no standard approach for the management of TNF inhibitor-induced psoriasis. Here, we conduct a literature review on TNF inhibitor-induced psoriasis and introduce a novel treatment algorithm for maintaining otherwise effective anti-TNF therapy versus switching to a different class as appropriate in the management of patients with IBD, RA, psoriasis, or PsA.

#50 Gestational exposure of tumor necrosis factor-α (TNF-α) inhibitor drugs

2019 ◽  
Vol 88 ◽  
pp. 149-150 ◽  
Author(s):  
Erkoseoglu Ilknur ◽  
Kadioglu Mine ◽  
Cavusoglu Irem ◽  
Sisman Mulkiye ◽  
Aran Turhan ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Gestational Exposure ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Tumor Necrosis Factor-α Production-Enhancing Properties of Novel Adamantylalkylthio Derivatives of Some Heterocyclic Compounds

2005 ◽  
Vol 60 (4) ◽  
pp. 471-475 ◽  
Author(s):  
Barbara Orzeszko ◽  
Tomasz Świtaj ◽  
Anna B. Jakubowska-Mućka ◽  
Witold Lasek ◽  
Andrzej Orzeszko ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Heterocyclic Compounds ◽  
Tumor Necrosis ◽  
The Novel ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Factor Α ◽  
Derivatives Of ◽  
Necrosis Factor

Certain adamantylated heterocycles were previously shown to enhance the secretion of tumor necrosis factor alpha (TNF-α) by murine melanoma cells that have been transduced with the gene for human TNF-α and constitutively expressed this cytokine. The stimulatory potency of those compounds depended, among other factors, on the structure of the linker between the adamantyl residue and the heterocyclic core. In the present study, a series of (1-adamantyl)alkylsulfanyl derivatives of heterocyclic compounds was prepared by alkylation of the corresponding thioheterocyles. Of the novel adamantylalkylthio compounds tested in the aforementioned cell line, 2-(2-adamantan-1-ylethylsulfanyl)- 4-methyl-pyrimidine was found to be the most active

scholarly journals Tumor necrosis factor α Inhibition for Alzheimer’s Disease

2017 ◽  
Vol 9 ◽  
pp. 117957351770927 ◽  
Author(s):  
Rudy Chang ◽  
Kei-Lwun Yee ◽  
Rachita K Sumbria
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Short Review ◽  
Tnf Α ◽  
Factor Α ◽  
Ad Therapy ◽  
Necrosis Factor

Tumor necrosis factor α (TNF-α) plays a central role in the pathophysiology of Alzheimer’s disease (AD). Food and Drug Administration–approved biologic TNF-α inhibitors are thus a potential treatment for AD, but they do not cross the blood-brain barrier. In this short review, we discuss the involvement of TNF-α in AD, challenges associated with the development of existing biologic TNF-α inhibitors for AD, and potential therapeutic strategies for targeting TNF-α for AD therapy.

Tumor necrosis factor-α-associated lysosomal permeabilization is cathepsin B dependent

2002 ◽  
Vol 283 (4) ◽  
pp. G947-G956 ◽  
Author(s):  
Nathan W. Werneburg ◽  
M. Eugenia Guicciardi ◽  
Steven F. Bronk ◽  
Gregory J. Gores
Keyword(s):  
Tumor Necrosis Factor ◽  
Cathepsin B ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Fluorescent Protein ◽  
Tnf Α ◽  
Calcein Release ◽  
Green Fluorescent ◽  
Factor Α ◽  
Necrosis Factor

Cathepsin B (Cat B) is released from lysososomes during tumor necrosis factor-α (TNF-α) cytotoxic signaling in hepatocytes and contributes to cell death. Sphingosine has recently been implicated in lysosomal permeabilization and is increased in the liver by TNF-α. Thus the aims of this study were to examine the mechanisms involved in TNF-α-associated lysosomal permeabilization, especially the role of sphingosine. Confocal microscopy demonstrated Cat B-green fluorescent protein and LysoTracker Red were both released from lysosomes after treatment of McNtcp.24 cells with TNF-α/actinomycin D, a finding compatible with lysosomal destabilization. In contrast, endosomes labeled with Texas Red dextran remained intact, suggesting lysosomes were specifically targeted for permeabilization. LysoTracker Red was released from lysosomes in hepatocytes treated with TNF-α or sphingosine in Cat B(+/+) but not Cat B(−/−) hepatocytes, as assessed by a fluorescence-based assay. With the use of a calcein release assay in isolated lysosomes, sphingosine permeabilized liver lysosomes isolated from Cat B(+/+) but not Cat B(−/−) liver. C6ceramide did not permeabilize lysosomes. In conclusion, these data implicate a sphingosine-Cat B interaction inducing lysosomal destabilization during TNF-α cytotoxic signaling.

Tumor Necrosis Factor-α −308 Genotypes Influence Inflammatory Activity and TNF-α Serum Concentrations in Children with Juvenile Idiopathic Arthritis

2009 ◽  
Vol 36 (4) ◽  
pp. 837-842 ◽  
Author(s):  
ANA FILIPA MOURÃO ◽  
JOANA CAETANO-LOPES ◽  
PAULA COSTA ◽  
HELENA CANHÃO ◽  
MARIA JOSÉ SANTOS ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Inflammatory Activity ◽  
Serum Concentrations ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Objective.Considering the relevance of tumor necrosis factor-α (TNF-α) in the pathophysiology of juvenile idiopathic arthritis (JIA), it is likely that polymorphisms in its promoter area may be relevant in disease susceptibility and activity. We investigated if clinical measures of JIA activity and TNF-α serum concentrations were associated with TNF-α −308 genotypes.Methods.Portuguese patients with JIA in 5 pediatric rheumatology centers were recruited consecutively, along with a control group of healthy subjects. Demographic and clinical data and blood samples were collected from each patient. DNA was extracted for analysis of TNF-α gene promoter polymorphisms at position −308 by restriction fragment-length polymorphism.Results.One hundred fourteen patients and 117 controls were evaluated; 57% of patients presented the oligoarticular subtype, 25% the polyarticular subtype, 8% the systemic subtype, and 9% had enthesitis-related arthritis and 5% psoriatic arthritis. Twenty-four percent of the patients presented the −308 GA/AA genotypes and 76% the −308 GG genotype, similar to findings in controls. Patients with the −308 GA/AA genotype had higher degree of functional impairment, erythrocyte sedimentation rate, 100-mm visual analog scale score for disease activity, and TNF-α levels compared to those with the −308 GG genotype.Conclusion.TNF-α −308 GA/AA genotypes were found to be related to higher inflammatory activity and worse measures of disease activity in Portuguese patients with JIA. They were not associated with susceptibility to JIA.

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