Longterm Efficacy of an Antipneumococcal Polysaccharide Vaccine among Patients with Autoimmune Inflammatory Rheumatic Diseases

Objective.To estimate the longterm humoral response of an antipneumococcal polysaccharide vaccine (PPSV23) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or inflammatory bowel disease (IBD)-associated spondyloarthropathy (SpA), and the effect of demographic and clinical factors and treatment on the longterm efficacy of the vaccine.Methods.A total of 145 consecutive patients treated with biologics [tumor necrosis factor-α (TNF-α) or interleukin 6 (IL-6) receptor inhibitors] or methotrexate (MTX) participated in this study. Fifteen were excluded because of absent information regarding their vaccination status (n = 9) or because of technical problems in obtaining their serum sample (n = 6). They were diagnosed with RA (n = 63, 48.5%), PsA (n = 29, 22.3%), AS (n = 28, 21.5%), or IBD-associated SpA (n = 3, 2.3%). Their mean age was 54.6 years, and 61.5% were women. Data were collected on the timing of vaccination, demographic and clinical characteristics, and treatment, and patients’ serum antipneumococcal antibody levels were tested.Results.Two-thirds of the patients (67.7%) had received PPSV23 45 months (mean) earlier. Treatment included TNF-α inhibitors (73.9%), IL-6 receptor inhibitors (13.1%), or MTX without a biological treatment (13%). The uptake of vaccination was significantly higher in the older population (> 65 yrs). Vaccinated patients had significantly higher antibody levels compared with vaccine-naive patients. The antibody levels had been preserved after 10 years. MTX use, but not biologics, was associated with significantly lower antibody levels.Conclusion.The longterm efficacy of the PPSV23 vaccination seems to be preserved among patients with RA, PsA, AS, and IBD-associated SpA for at least 10 years. Efficacy is slightly impaired by MTX, but it is not affected by biologics. These findings suggest that revaccination after 5 years might not be needed for all, and testing the antibody titers should be considered to identify those who may benefit from revaccination.

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

Pharmaceutics ◽

10.3390/pharmaceutics12060539 ◽

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.

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Effects of tumor necrosis factor α on leptin-sensitive intestinal vagal mechanoreceptors in the cat

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2013-0025 ◽

2013 ◽

Vol 91 (11) ◽

pp. 941-950 ◽

Cited By ~ 3

Author(s):

Nathalie Quinson ◽

Véronique Vitton ◽

Michel Bouvier ◽

Jean-Charles Grimaud ◽

Anne Abysique

Keyword(s):

Tumour Necrosis ◽

Discharge Frequency ◽

Tumour Necrosis Factor Α ◽

Tnf Α ◽

Inflammatory Bowel ◽

Pre Treatment ◽

Factor Α ◽

Necrosis Factor

The involvement of tumour necrosis factor α (TNF-α) in inflammatory bowel disease (IBD) has been established, and anti-TNF-α has been suggested as a therapeutic approach for the treatment of these pathologies. We studied the effects of TNF-α on leptin-sensitive intestinal vagal units to determine whether TNF-α exerts its effects through the intestinal vagal mechanoreceptors and to investigate its interactions with substances regulating food intake. The activity of intestinal vagal mechanoreceptors was recorded via microelectrodes implanted into the nodose ganglion in anesthetized cats. TNF-α (1 μg, i.a.) increased the discharge frequency of leptin-activated units (type 1 units; P < 0.05) and had no effect on the discharge frequency of leptin-inhibited units (type 2 units). When TNF-α was administered 20 min after sulfated cholecystokinin-8 (CCK), its excitatory effects on type 1 units were significantly enhanced (P < 0.0001) and type 2 units were significantly (P < 0.05) activated. Pre-treatment with Il-1ra (250 μg, i.a.) blocked the excitatory effects of TNF-α on type 1 units whereas the excitatory effects of TNF-α administration after CCK treatment on type 2 units were not modified. The activation of leptin-sensitive units by TNF-α may explain, at least in part, the weight loss observed in IBD.

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P415 Paradoxical onset of Takayasu’s arteritis in patients with inflammatory bowel disease treated with anti-tumour necrosis factor-α agents

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.539 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S422-S422

Author(s):

Y Matsune ◽

J Kouyama ◽

Y Tsuru ◽

K Shimizu ◽

S Asami ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Clinical Features ◽

Bowel Disease ◽

Tumour Necrosis ◽

Rare Complication ◽

Tumour Necrosis Factor Α ◽

Tnf Α ◽

Inflammatory Bowel ◽

Factor Α ◽

Necrosis Factor

Abstract Background Takayasu’s arteritis (TA) is a rare complication associated with inflammatory bowel disease (IBD). TA is a granulomatous systemic vasculitis of uncertain aetiology affecting large arteries, predominantly the aorta and its main branches, leading to stenotic and expansible lesions. The estimated prevalence of coexisting of TA in patients with ulcerative colitis (UC) is 0.3%, and that in patients with Crohn’s disease (CD) is 0.1%. Anti-tumour necrosis factor-α (TNF-α) agents are used to treat both TA and IBD, although some patients with IBD paradoxically develop TA during treatment with anti-TNF-α agents. However, data regarding the incidence and clinical features of TA in such cases are lacking. This study was performed to clarify the prevalence, risk factors, and clinical features of TA that develops paradoxically during treatment with anti-TNF-α agents in patients with IBD. Methods Consecutive patients with IBD who were regularly seen at our centre, a tertiary IBD centre in Japan, from 2000 to 2019 were included in this retrospective single-centre study. We evaluated the prevalence of TA according to the presence or absence of treatment with anti-TNF-α agents and the patients’ clinical manifestations. Results Of 1846 patients with UC and 1249 patients with CD, 7 (0.23%) patients with UC developed TA. The prevalence of TA in patients treated with anti-TNF-α agents was significantly higher (4/254, 1.6%) than that in patients without anti-TNF-α agent treatment (3/1592, 0.19%) (p=0.0087, Fisher’s exact test). Among four patients with UC who paradoxically developed TA during treatment with anti-TNF-α agents, three (75%) received infliximab, one (25%) received adalimumab, and one (25%) received golimumab. One was male and three (75%) were female. The median interval from starting treatment with anti-TNF-α agents to diagnosis of TA was 49.0 (34–63) months. All patients had pancolitis as well as persistent active colitis resistant to anti-TNF-α antibody treatment. The treatments for TA administered after anti-TNF-α therapy were as follows: Two (50%) patients discontinued anti-TNF-α agent therapy, three (75%) were treated with prednisolone, and one (25%) received tocilizumab. No patient required an operation for TA. Conclusion To our knowledge, this is the first study to show the prevalence and clinical features of TA in patients with IBD following administration of anti-TNF-α agent therapy. Although TA is a rare complication, our results suggest that it can develop as paradoxical reaction following administration of anti-TNF-α agents.

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Food and Drug Administration guidances on biosimilars: an update for the gastroenterologist

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284818799600 ◽

2018 ◽

Vol 11 ◽

pp. 175628481879960 ◽

Cited By ~ 3

Author(s):

Michael Epstein

Keyword(s):

Drug Administration ◽

Food And Drug Administration ◽

The United States ◽

Biologic Therapies ◽

Tnf Α ◽

The Us ◽

Guidance Documents ◽

Inflammatory Bowel ◽

Factor Α ◽

Necrosis Factor

The management of inflammatory bowel disease (IBD), a significant cause of morbidity in the United States (US), has been revolutionized over the last two decades by the introduction of biologic therapies. These include antitumor necrosis factor α (TNF-α) agents. Since 2016, five biosimilar TNF-α inhibitors have been approved by the US Food and Drug Administration (FDA) for use in the treatment of IBD. The FDA has published a series of guidance documents related to the evaluation, licensing, and approval of biosimilars. The aim of this review is to provide an overview of these FDA guidances and the issues associated with biosimilars in the US.

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

Medical alphabet ◽

10.33667/2078-5631-2021-16-47-52 ◽

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.

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Antitumor Necrosis Factor-α Therapy Associated with Inflammatory Bowel Disease: Three Cases and a Systematic Literature Review

The Journal of Rheumatology ◽

10.3899/jrheum.160952 ◽

2017 ◽

Vol 44 (7) ◽

pp. 1088-1095 ◽

Cited By ~ 6

Author(s):

Amir Bieber ◽

Abdallah Fawaz ◽

Irina Novofastovski ◽

Reuven Mader

Keyword(s):

Inflammatory Bowel Disease ◽

Literature Review ◽

Bowel Disease ◽

Gastrointestinal Symptoms ◽

Case Series ◽

Patient Specific ◽

Tnf Α ◽

Inflammatory Bowel ◽

Factor Α ◽

Necrosis Factor

Objective.Antitumor necrosis factor-α (anti-TNF-α) therapy is the most prescribed biologic agent therapy in rheumatology and gastroenterology. However, a number of serious side effects have been reported with these drugs. Only a handful of cases of new-onset inflammatory bowel disease (IBD), mostly in children diagnosed with juvenile idiopathic arthritis (JIA), have been reported during anti-TNF-α therapy. We present 3 cases of adult IBD following anti-TNF-α therapy and a literature review on this topic.Methods.We searched PubMed MESH for all relevant terms, papers were reviewed, and patient-specific data were extracted. Relevant clinical data were calculated and presented.Results.The PubMed search resulted in 137 articles, of which 11 articles and 4 cited publications were included in our analysis. We found 53 cases of IBD after anti-TNF-α therapy reported in the literature; most of them were case series collected retrospectively from national databases or studies. Almost all the patients developed IBD after the introduction of etanercept (ETN); 2 patients with rheumatoid arthritis were also included. The average age at IBD onset was 17.3 years and the average time from ETN introduction to IBD onset was 27 months (± 24). Gastrointestinal symptoms have been reported as improving or subsiding in most of the patients after discontinuing ETN.Conclusion.Although this manifestation is not common, it should be taken into consideration as an adverse effect of ETN. Rheumatologists, and in particular rheumatologists treating adult patients, should be aware of this possible complication. Further investigation about the pathogenic process underlying this phenomenon is warranted.

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Mycobacterial diseases developed during anti-tumour necrosis factor-α therapy

European Respiratory Journal ◽

10.1183/09031936.00063514 ◽

2014 ◽

Vol 44 (5) ◽

pp. 1289-1295 ◽

Cited By ~ 22

Author(s):

Jung-Wan Yoo ◽

Kyung-Wook Jo ◽

Bo-Hyung Kang ◽

Mi Young Kim ◽

Bin Yoo ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Tumour Necrosis Factor ◽

Tumour Necrosis ◽

Clinical Characteristics ◽

Underlying Disease ◽

Radiological Feature ◽

Tnf Α ◽

Inflammatory Bowel ◽

Factor Α ◽

Necrosis Factor

Nontuberculous mycobacterial (NTM) disease and tuberculosis (TB) develop during anti-tumour necrosis factor (TNF)-α therapy. We compared clinical characteristics and outcomes between the two diseases.A total of 1165 patients were screened for TB and treated with TNF-α antagonists from July 2004 to July 2013 for the following conditions: inflammatory bowel disease (n = 422), rheumatoid arthritis (n = 320), and ankylosing spondylitis (n = 389).TB and NTM disease were diagnosed at baseline screening in four and three patients, respectively, and developed during anti-TNF-α therapy in 19 and six patients, respectively. The incidence rate of TB and NTM disease was 747.7 per 100 000 and 238.2 per 100 000 person-years, respectively. Patients with NTM disease were older, with a greater proportion of females. All cases of NTM disease involved the lung, with rheumatoid arthritis (83.3%) being the most frequent underlying disease. The most common radiological feature was consolidation in NTM disease, and honeycombing was present in two rheumatoid arthritis patients with NTM disease. The most common pathogen wasMycobacterium intracellulare(n = 3) followed byMycobacterium avium(n = 2). Both the NTM and TB group showed favourable outcomes.The clinical characteristics differed between NTM disease and TB that developed on anti-TNF-α agents, but clinical outcomes were favourable in both diseases.

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

Clinical Chemistry ◽

10.1093/clinchem/47.7.1297 ◽

2001 ◽

Vol 47 (7) ◽

pp. 1297-1301 ◽

Cited By ~ 140

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 <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.

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Acyclic Triterpenoid Isolated from Alpinia katsumadai Alleviates Formalin-Induced Chronic Mouse Paw Inflammation by Inhibiting the Phosphorylation of ERK and NF-κB

Molecules ◽

10.3390/molecules25153345 ◽

2020 ◽

Vol 25 (15) ◽

pp. 3345 ◽

Cited By ~ 1

Author(s):

Hyung Jin Lim ◽

Seon Gyeong Bak ◽

Hee Ju Lim ◽

Seung Woong Lee ◽

Soyoung Lee ◽

...

Keyword(s):

Mouse Model ◽

Inflammatory Diseases ◽

Extracellular Signal ◽

Tnf Α ◽

J774 Cells ◽

Inflammatory Bowel ◽

Anti Inflammatory ◽

Factor Α ◽

Necrosis Factor

Chronic and excessive inflammation can destroy host organs and cause inflammatory diseases such as inflammatory bowel disease, asthma, and rheumatoid arthritis. In this study, we investigated the anti-inflammatory effects of Alpinia katsumadai seed-derived 2,3,5,22,23-pentahydroxy-2,6,10,15,19,23-hexamethyl-tetracosa-6,10,14,18-tetraene (PHT) using lipopolysaccharide (LPS)-stimulated J774 cells and a formalin-induced chronic paw inflammation mouse model. The in vitro results showed that PHT exhibited no cytotoxicity and decreased LPS-induced NO secretion. Additionally, PHT inhibited LPS-induced inducible NO synthase (iNOS) and cyclooxygenase 2 (COX2) protein expression. The quantitative real-time PCR results showed that PHT downregulated the gene expression of the proinflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6) but not tumor necrosis factor α (TNF-α). PHT inhibited the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB). In a mouse model, oral administration of 50 mg/kg PHT significantly alleviated both mouse paw thickness and volume. These results indicate that PHT has potential anti-inflammatory effects and should be considered a possible functional material.

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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

Digestive Diseases ◽

10.1159/000506121 ◽

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

Background: 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. Methods: This study included patients aged ≥18 years who had received prescriptions for second-line biological drugs in Germany between 2014 and 2017 (n = 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. Results: 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 p = 0.005). The corresponding figures were 27.8 and 20.8% in the vedolizumab-golimumab matched-pair analysis (log-rank p < 0.001) and 29.5 and 25.2% in the vedolizumab-infliximab matched-pair analysis (log-rank p 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. Conclusions: Treatment persistence was higher for vedolizumab than for TNF-α inhibitors up to 3 years after initiating second-line biological therapy.

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