Dosage Adjustment of Anti-Tumor Necrosis Factor-α Inhibitor in Ankylosing Spondylitis Is Effective in Maintaining Remission in Clinical Practice

2012 ◽  
Vol 39 (7) ◽  
pp. 1418-1423 ◽  
Author(s):  
JULIEN PACCOU ◽  
MARIE-ASTRID BACLÉ-BOUTRY ◽  
ELISABETH SOLAU-GERVAIS ◽  
PEGGY BELE-PHILIPPE ◽  
RENÉ-MARC FLIPO
Keyword(s):  
Ankylosing Spondylitis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Dosage Adjustment ◽  
Treatment Frequency ◽  
Response Predictors ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Objective.While remission is possible in patients with ankylosing spondylitis (AS), it is often unclear what attitude should be adopted once remission has occurred. We investigated whether dosage adjustment is an effective means of maintaining remission.Methods.This was a retrospective study drawn from clinical situations. Remission was defined using clinical measures [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≤ 20/100 and no peripheral joint disease] and biological measures [C-reactive protein (CRP) levels ≤ normal value]. The tumor necrosis factor-α (TNF-α) inhibitors used were infliximab, adalimumab, and etanercept. Response predictors of remission were evaluated by logistic regression (age, CRP, HLA-B27 positivity, sex, duration of disease, and anti-TNF-α naivety). CRP and BASDAI were evaluated before and after dosage adjustment at about 6, 12, 24, and 36 months.Results.One hundred eighty-nine patients with AS were included in the study, with a mean followup of 43.5 (± 17.9) months after the introduction of the first anti-TNF-α inhibitor. Mean age was 45.6 (± 12.5) years. Remission had occurred in 65 patients (35%). Significant response predictors of remission were male sex (p = 0.003) and anti-TNF-α naivety (p < 0.001). Dosage adjustment was observed 49 times, and progressively reducing treatment frequency was effective to maintain remission in a large number of patients for 36 months. The cumulative probability of continuing anti-TNF-α after dosage adjustment was 79.0% at 12 months, 70.5% at 24 months, and 58.8% at 36 months.Conclusion.Remission had occurred in 35% of the patients with AS under anti-TNF-α inhibitor therapy. Dosage adjustment and progressively reducing treatment frequency was effective in maintaining remission.

scholarly journals Association of adipokines, interleukin-6, and tumor necrosis factor-α concentrations with clinical characteristics and presence of spinal syndesmophytes in patients with ankylosing spondylitis: A cross-sectional study

2017 ◽  
Vol 45 (3) ◽  
pp. 1024-1035 ◽  
Author(s):  
Laura Gonzalez-Lopez ◽  
Nicte S. Fajardo-Robledo ◽  
A. Miriam Saldaña-Cruz ◽  
Inocente V. Moreno-Sandoval ◽  
David Bonilla-Lara ◽  
...  
Keyword(s):  
Body Composition ◽  
Ankylosing Spondylitis ◽  
Tumor Necrosis Factor ◽  
Clinical Characteristics ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Serum Leptin ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Objective To identify correlations of the serum leptin, adiponectin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) concentrations with the clinical characteristics, presence of spinal syndesmophytes, and body composition in patients with ankylosing spondylitis (AS). Methods Forty-eight patients with AS were compared with 41 sex- and age-matched controls. Assessment included clinical characteristics and the presence of spinal syndesmophytes. The serum leptin, adiponectin, TNF-α, and IL-6 concentrations were determined. Body composition was evaluated using dual-energy X-ray absorptiometry. Results Patients with AS and controls had similar fat mass and lean mass. Patients with AS had higher serum TNF-α and leptin concentrations than controls (52.3 vs. 1.5 pg/mL and 17.2 vs. 9.0 µg/mL, respectively). The IL-6 and adiponectin concentrations were not significantly different between the two groups. Patients with syndesmophytes had higher leptin concentrations than those without syndesmophytes (22.1 vs. 10.9 µg/mL); this difference remained after adjustment for the body mass index. Conclusion Elevated leptin concentrations are associated with spinal radiographic damage in patients with AS and can serve as a biomarker. Future studies should evaluate whether leptin might be a potential target for treatments to avoid structural damage.

Fat Mass Lowers the Response to Tumor Necrosis Factor-α Blockers in Patients with Ankylosing Spondylitis

2017 ◽  
Vol 44 (9) ◽  
pp. 1355-1361 ◽  
Author(s):  
Sebastián E. Ibáñez Vodnizza ◽  
Michael T. Nurmohamed ◽  
Ingrid M. Visman ◽  
J. Christiaan van Denderen ◽  
Willem F. Lems ◽  
...  
Keyword(s):  
Body Composition ◽  
Ankylosing Spondylitis ◽  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Body Fat ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Objective.Our main objective was to assess the relationship between body composition (BC) and response to tumor necrosis factor-α (TNF-α) blocker treatment in patients with ankylosing spondylitis (AS). Our secondary objective was to evaluate the change of BC after treatment, accounting for sex and age.Methods.All included patients fulfilled the modified New York criteria for AS and were naive to TNF-α blocker. They were followed for at least 6 months after the start of etanercept or adalimumab. The Ankylosing Spondylitis Disease Activity Score containing C-reactive protein (ASDAS-CRP) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were reported. BC was assessed by whole body dual-energy X-ray absorptiometry. Body fat percentage (BF%), fat mass index (FMI), and fat free mass index (FFMI) were reported as absolute values and as percentiles.Results.Forty-one patients were included (61% men). The median followup was 14.3 months (interquartile range 8.4–19.4). After multivariate regression analysis, more fat at baseline (BF%, FMI, or FMI percentile) was significantly related with a lower chance of achieving a clinically important improvement of the ASDAS-CRP or BASDAI after treatment. The body composition did not change significantly after treatment, but there was a trend toward muscle recovery in men (FFMI change from 34.0th to 37.4th percentile).Conclusion.Higher body fat content at baseline was independently associated with a worse response to treatment with TNF-α blockers, measured by ASDAS-CRP and BASDAI change, and might contribute to the lower response rates in female patients. Also, there is a trend toward muscle mass recovery in male patients after treatment.

In Vivo Peripheral Blood Proinflammatory T Cells in Patients with Ankylosing Spondylitis

2012 ◽  
Vol 39 (4) ◽  
pp. 830-835 ◽  
Author(s):  
LEONARDO LIMÓN-CAMACHO ◽  
MARÍA INÉS VARGAS-ROJAS ◽  
JANITZIA VÁZQUEZ-MELLADO ◽  
JULIO CASASOLA-VARGAS ◽  
JOSÉ F. MOCTEZUMA ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Th1 Cells ◽  
Healthy Controls ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Objective.Previous reports have shown an increase in peripheral blood mononuclear cells’ (PBMC) Th17 cell subpopulation and tumor necrosis factor-α (TNF-α) secretion after in vitro stimulation with anti-CD3/CD28 or phorbol myristate acetate/ionomycin in ankylosing spondylitis (AS). The aim of our study was to determine whether there is a Th17 polarization not subjected to in vitro stimulation in patients with AS.Methods.Nonstimulated PBMC were analyzed from 46 patients with AS, including 7 (15.2%) receiving tumor necrosis factor-α (TNF-α) inhibitors, 20 patients with rheumatoid arthritis, and 25 healthy controls. The surface phenotype of freshly isolated PBMC was determined by flow cytometry. Th1, Th2, Th17, and Treg subsets were defined as CD3+CD4+IFN-γ+, CD3+CD4+IL-4+, CD3+CD4+IL-17A+, and CD3+CD4+FoxP3+, respectively. Serum cytokines and interleukin 8 (IL-8) levels were quantified by Luminex technology.Results.The percentages of Th17 and Th1 cells in AS were higher than in healthy controls (7.4% ± 1.8% vs 0.7% ± 0.2% and 4.0% ± 1.3% vs 1.1% ± 0.3%, respectively; p < 0.0001). Th17 and Th1 cell subsets in patients taking TNF-α inhibitors were lower than in those naive to such therapeutics and similar to healthy controls. Serum levels of IL-6, IL-17A, TNF-α, and IL-8 were significantly higher in patients with AS compared to controls.Conclusion.The percentages of Th17 and Th1 cells in PBMC without in vitro stimulation, as well as cytokine and IL-8 levels, were significantly increased in patients with AS compared with healthy controls. These T cell subsets and cytokine profiles of patients with AS taking TNF-α inhibitors were similar to those of healthy controls.

scholarly journals The interchangeability of original tumor necrosis factor- α inhibitors and biosimilars in rheumatology: experience in replacing original infliximab with Flammagis for ankylosing spondylitis

2020 ◽  
Vol 14 (2) ◽  
pp. 104-109
Author(s):  
Yu. V. Muravyev ◽  
V. V. Lebedeva ◽  
A. S. Starkova ◽  
D. G. Rumyantseva ◽  
M. M. Urumova ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Quality Care ◽  
Pharmacovigilance System ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor ◽  
Clinical Cases

The paper discusses prospects for prescribing tumor necrosis factor-α (TNF-α) inhibitor biosimilars, their interchangeability with original drugs for inflammatory joint diseases. It describes clinical cases when original infliximab is replaced with its biosimilar Flammagis for ankylosing spondylitis. The authors emphasize that it is difficult to predict the interchangeability of original TNF-α inhibitors and biosimilars in rheumatology, and this is confirmed by the above clinical cases. They also indicate that the optimal use of biosimilars requires a constant cooperation of rheumatologists, pharmacologists, and regulatory authorities, which is aimed at protecting the rights of a patient in order to ensure safe, effective and high-quality care. It is concluded that it is advisable to conduct further investigations to develop a special pharmacovigilance system in this area.

#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

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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