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2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Kosuke Ebina ◽  
Toru Hirano ◽  
Yuichi Maeda ◽  
Wataru Yamamoto ◽  
Motomu Hashimoto ◽  
...  

AbstractThis multi-center, retrospective study aimed to clarify the factors affecting drug retention of the Janus kinase inhibitors (JAKi) including baricitinib (BAR) and tofacitinib (TOF) in patients with RA. Patients were as follows; females, 80.6%; age, 60.5 years; DAS28-ESR, 4.3; treated with either BAR (n = 166) or TOF (n = 185); bDMARDs- or JAKi-switched cases (76.6%). The reasons for drug discontinuation were classified into four major categories. The drug retention was evaluated at 24 months using the Kaplan–Meier method and multivariate Cox proportional hazards modelling adjusted by confounders. Discontinuation rates for the corresponding reasons were as follows; ineffectiveness (22.3%), toxic adverse events (13.3%), non-toxic reasons (7.2%) and remission (0.0%). Prior history of anti-interleukin-6 receptor antibody (aIL-6R) ineffectiveness significantly increased the risk of treatment discontinuation due to ineffectiveness (p = 0.020). Aging (≥ 75 years) (p = 0.028), usage of PSL ≥ 5 mg/day (p = 0.017) and female sex (p = 0.041) significantly increased the risk of treatment discontinuation due to toxic adverse events. Factors not associated with treatment discontinuation were: number of prior bDMARDs or JAKi, concomitant MTX usage, difference of JAKi, and prior use of TNF inhibitor, CTLA4-Ig or other JAKi.


2021 ◽  
Vol 11 (1) ◽  
pp. 55
Author(s):  
Georgiana Strugariu ◽  
Cristina Pomîrleanu ◽  
Codruța Bran ◽  
Andrei Costea ◽  
Andrei Vicovan ◽  
...  

(1) Background: Recent data shed light on the association between atopic disorders (ADs) (atopic dermatitis, allergic asthma, allergic rhinitis) and spondyloarthropathies (SpAs), underpinning the critical role of T helper (Th)1-Th17/Th2-T regulatory cells disbalance. We evaluated the prevalence of AD in axial SpAs (axSpAs) and psoriatic arthritis (PsA) and explored the potential association between atopic status, disease-related parameters, and biological therapy. (2) Methods: A monocentric, retrospective study was conducted that enrolled 200 patients taking biologics. Demographics, disease, and drug-related variables, along with a screening questionnaire focused on Ads, were systematically collected. (3) Results: Overall, 51 patients (25.5%) had atopy—namely, 24.4% of axSpA and 28% of PsA, with a higher frequency of rhinitis (43%) vs. atopic dermatitis (37.2%) or asthma (21.5%). We failed to demonstrate any statistically significant difference in demographics, SpA-related parameters excepting concomitant inflammatory bowel disease, and biologic drug exposure in patients with and without atopy (p > 0.05). However, significantly more non-atopic patients need only one TNF inhibitor (54%) vs. atopic patients (28%) (p < 0.05) to control active SpA. (4) Conclusions: We successfully demonstrated that AD is associated with one out of four SpA. Irrespective of the SpA subtype, atopic patients require more frequent switching among biologics, as significantly more non-atopic patients remain on their first anti-TNF.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ke Gong ◽  
Gao Guo ◽  
Nicole A. Beckley ◽  
Xiaoyao Yang ◽  
Yue Zhang ◽  
...  

AbstractInhibition of RTK pathways in cancer triggers an adaptive response that promotes therapeutic resistance. Because the adaptive response is multifaceted, the optimal approach to blunting it remains undetermined. TNF upregulation is a biologically significant response to EGFR inhibition in NSCLC. Here, we compared a specific TNF inhibitor (etanercept) to thalidomide and prednisone, two drugs that block TNF and also other inflammatory pathways. Prednisone is significantly more effective in suppressing EGFR inhibition-induced inflammatory signals. Remarkably, prednisone induces a shutdown of bypass RTK signaling and inhibits key resistance signals such as STAT3, YAP and TNF-NF-κB. Combined with EGFR inhibition, prednisone is significantly superior to etanercept or thalidomide in durably suppressing tumor growth in multiple mouse models, indicating that a broad suppression of adaptive signals is more effective than blocking a single component. We identify prednisone as a drug that can effectively inhibit adaptive resistance with acceptable toxicity in NSCLC and other cancers.


Author(s):  
Alla Ishchenko ◽  
Johan Joly ◽  
Neerinckx Barbara ◽  
Rik Lories ◽  
Kurt de Vlam

Abstract Objectives Biological treatments revolutionized the management of psoriatic arthritis (PsA) by significantly improving clinical manifestations and preventing structural damage. Both result in better quality of life and improved physical functioning. Since the introduction of the first TNF inhibitor (TNFi) in the early 2000s, therapeutic options for PsA are increasing steadily and a new generation of biologicals, including anti interleukin (IL)-17 and anti IL23 strategies, allows distinct targeted approaches. The purpose of this study was to investigate whether the demographic, clinical and disease characteristics of PsA patients that are selected for first-line biological treatment, changed over time since the introduction of biologicals. Methods Patients with a clinical diagnosis of PsA were included in the KU Leuven BioSPAR registry, a prospective cohort of spondyloarthritis (SpA) and PsA patients treated with biologicals and targeted synthetic disease modifying anti-rheumatic drugs (tsDMARDs) such as apremilast and JAK inhibitors. Demographics, prior DMARD use, disease characteristics and disease activity parameters were recorded at the initiation of biological treatment and subsequently every 3-months for the first 2 years and later every 6 months. The patient data were compared in three treatment periods, corresponding with availability of the first and the second generation of TNF inhibitors and the third generation of biologicals. Results Analysis of 185 Caucasian patients with PsA from our prospective cohort showed longer disease duration and higher disease activity with higher tender joint count (TJC), swollen joint count (SJC) and higher CRP in the first as compared with the later time periods. The demographic characteristics and prior DMARD use did not change over time. Skin and nail psoriasis were more frequent in earlier compared with the later treatment periods. The bio-DMARD survival rate was similar in the early and later treatment periods. Conclusion The population of patients, selected for treatment escalation, changed over time since the introduction of biologicals. Our results suggest that with years of experience, PsA patients might be considered earlier and for therapy intensification in patients with less active disease as compared with profiles in the early days of biological treatment.


2021 ◽  
Vol 97 (4) ◽  
pp. 113-119
Author(s):  
Maria N. Chamurlieva ◽  
Yulia L. Korsakova ◽  
Stefka G. Radenska-Lopovok ◽  
Tatiana V. Korotaeva

Biological disease-modifying anti-rheumatic drugs (bDMARDs) are widely used for the treatment of chronic inflammatory rheumatic diseases. Since the introduction of tumor necrosis factor alpha (TNF-) inhibitors, the treatment of rheumatoid arthritis has been revolutionized. The approach of targeting TNF- has considerably improved the success of the treatment of rheumatoid arthritis. Their effectiveness has been extensively proven in randomized clinical trials and in clinical practice. Randomized clinical trials and post-marketing studies proved that patients undergoing TNF- inhibitors therapy are at increased risk of infectious disease, bacterial, viral, fungal, opportunistic, oncology and skin adverse effects such as psoriasis and angiitis of the skin. In this case report drug-induced cutaneous vasculitis developing during TNF- inhibitor (Etanercept) treatment for rheumatoid arthritis is described.


2021 ◽  
Author(s):  
Boyoon Choi ◽  
Hyun Jin Park ◽  
Yun-Kyoung Song ◽  
Yoon-Jeong Oh ◽  
In-Wha Kim ◽  
...  

Abstract Background Tumor necrosis factor (TNF) inhibitors use in patients with rheumatoid arthritis (RA) has raised safety concerns about cancer risk, but study results remain controversial. This largest nationwide study to date compared cancer risk in TNF inhibitor users to non-biologic disease-modifying anti-rheumatic drug (nbDMARD) users in Korean patients with RA. Methods Data on all the eligible patients diagnosed with RA between 2005 and 2016 were retrieved from the Korean National Health Information Database. The one-to-one matched patients consisted of the matched cohort. The risks for developing all-type and site-specific cancers were estimated using incidence and incidence rate (IR) per 1,000 person-years. Adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using a Cox regression model. Results Of the 22,851 patients in the before matching cohort, 4,592 patients were included in the matched cohort. Treatment with TNF inhibitors was consistently associated with a lower risk of cancer than in the nbDMARD cohort (IR per 1,000 person-years, 6.5 vs. 15.6; adjusted HR, 0.379; 95% CI, 0.255–0.563). The adjusted HR (95% CI) was significantly lower in the TNF inhibitor cohort than the nbDMARD cohort for gastrointestinal cancer (0.432; 0.235–0.797), breast cancer (0.146; 0.045–0.474), and genitourinary cancer (0.220; 0.059–0.820). Conclusions The use of TNF inhibitors was associated with a lower cancer incidence in Korean patients with RA. A further study linking claims and clinical data is needed to confirm our results.


2021 ◽  
Vol 10 (20) ◽  
pp. 4655
Author(s):  
Soo-Kyung Cho ◽  
Jun Liu ◽  
Yinzhu Jin ◽  
Seoyoung C. Kim

Objective: To evaluate the risk of non-vertebral fractures in patients with gout compared with those with rheumatoid arthritis (RA). Methods: Using claims data from Medicare (2008–2015), we conducted a cohort study of patients with gout versus RA matched on age, sex, and index date with a 1:1 ratio. The primary outcome was a composite endpoint of non-vertebral fractures including hip, pelvis, humerus, and wrist identified with the validated algorithms. We also assessed hip fractures separately. Multivariable Cox proportional hazards regression estimated the hazard ratio (HR) for the outcomes in gout versus RA adjusted for 45 covariates. Results: We included a total of 134,157 matched pairs of gout and RA patients (mean age: 73.7 years). Risk factors for fracture were more prevalent in RA, while other comorbidities including obesity, coronary heart disease, hypertension, and diabetes were more common in gout. Over the mean 2.8 years follow-up, the incidence rate (IR)/1000 person-year (PY) of non-vertebral fractures was 10.42 in gout and 15.01 in RA. For hip fractures, the IR/1000 PY was 4.86 in gout and 7.73 in RA. The multivariable HR associated with gout versus RA was 0.84 (95% confidence interval (CI) 0.80–0.88) for non-vertebral fractures and 0.76 (95% CI 0.71–0.82) for hip fractures. Stratified analyses by age, sex, prior fractures, steroid use, and TNF inhibitor use showed similar results. Conclusions: In this large cohort of older patients, gout was associated with a modestly decreased risk of non-vertebral or hip fractures versus RA. However, non-vertebral fractures occurred frequently in both gout and RA.


2021 ◽  
pp. annrheumdis-2021-221036
Author(s):  
Nafise Ghalandari ◽  
Erik Kemper ◽  
Ineke (Hubertina) Crijns ◽  
Gertjan Wolbink ◽  
Theo Rispens ◽  
...  

BackgroundTo minimise placental transfer of tumour necrosis factor inhibitors (TNFi), the European League Against Rheumatism (EULAR) created points to consider (PtC) for the use of TNFi during pregnancy. We are the first to validate the EULAR-PtC by analysing TNFi concentrations in cord blood.MethodsPatients were derived from the Preconceptional Counselling in Active Rheumatoid Arthritis Study. TNFi was stopped at the time points recommended by the EULAR. Maternal blood and cord blood were collected and analysed for the concentration of TNFi.Results111 patients were eligible for the analysis. Median stop time points were gestational age (GA) 37.0 weeks for certolizumab pegol, GA 25.0 weeks for etanercept, GA 19.0 weeks for adalimumab and GA 18.4 weeks for infliximab. Certolizumab pegol (n=68) was detectable in 5.9% of cord blood samples, with a median concentration of 0.3 µg/mL (IQR: 0.2–1.3) and a median cord/maternal concentration ratio of 0.010. Etanercept (n=30) was not detected in any cord blood samples. Adalimumab (n=25) was detectable in 48.0% of cord blood samples, with a median concentration of 0.5 µg/mL (IQR: 0.2–0.7) and a median concentration ratio of 0.062 (IQR: 0.018–0.15). Infliximab (n=14) was detectable in 57.1% of cord blood samples, with a median concentration of 0.4 µg/mL (IQR: 0.1–1.2) and a median concentration ratio of 0.012 (IQR: 0.006–0.081).ConclusionCompliance with the EULAR-PtC results in absence or low levels of TNFi in cord blood.


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