scholarly journals P671 Effect of genetic polymorphisms in the folate pathway on the efficacy and safety of methotrexate in Crohn’s disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S593-S593
Author(s):  
J Salazar ◽  
J Gordillo Abalos ◽  
A Fernández ◽  
M Esteve ◽  
J Pérez Gisbert ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Events ◽  
Genetic Polymorphisms ◽  
Multivariable Analysis ◽  
Efficacy And Safety ◽  
Second Line Therapy ◽  
Steroid Dependent ◽  
Folate Pathway ◽  
Maintenance Of Remission

Abstract Background Methotrexate (MTX) is currently used in steroid-dependent patients with moderate-to-severe Crohn’s disease (CD) when thiopurines have failed or are contraindicated. Although its efficacy has been proved for both induction and maintenance of remission, its use is limited due to the rate of associated adverse events. Polymorphisms in the folate pathway might predict the efficacy and toxicity of MTX. Our aims were to evaluate the predictive value of these polymorphisms of MTX efficacy and safety in CD. Methods Patients from ENEIDA registry of GETECCU who were treated with MTX on monotherapy and of whom genomic DNA was available, were identified. Clinical efficacy and MTX-related toxicity were collected, and 10 variants from ATIC, DHFR, MTHFR, RFC1, ABCB1 and ABCC3 genes were genotyped with TaqMan assays. Results One hundred and twenty nine patients were included, 55% were female and 31% active smokers. MTX was used as first and second-line therapy in 10% and 60% of patients, respectively, at a mean dose of 22 mg and for a median time of 14 months. Thirty-seven per cent of patients achieved clinical remission, whereas 34% were non-responders (MTX failure). Forty patients (30%) developed MTX-related toxicity, with nausea and vomiting, myelotoxicity and hepatotoxicity as the most frequent adverse events (37%, 15% and 15%, respectively). MTX was discontineud in 19% of the patients due to toxicity. In the multivariable analysis, patients with the AA genotype for the rs408626 DHFR variant was predictive of a higher efficacy as compared to the G allele carriers (RR 0.372, p=0.026), and smoking was associated with a higher risk of MTX therapy failure (RR 2.676, p=0.015). Moreover, the CC genotype for the rs1476413 MTHFR variant and the TT genotype for the rs4793665 ABCC3 variant were independently associated with a higher risk of MTX toxicity (RR 2.357, p=0.038 and RR 2.368, p=0.044, respectively). Conclusion Genetic polymorphisms related to the folate pathway (mainly the variant rs408626 of DHFR, rs1476413 of MTHFR and rs4793665 of ABCC3) seem to impact on MTX efficacy and toxicity in CD. Smoking could also influence MTX efficacy.

scholarly journals Anti-TNFα-terápiában részesülő gyulladásos bélbetegek hosszú távú utánkövetése

2020 ◽  
Vol 161 (47) ◽  
pp. 1989-1994
Author(s):  
Péter Bacsur ◽  
Soma Skribanek ◽  
Ágnes Milassin ◽  
Klaudia Farkas ◽  
Renáta Bor ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Treatment Period ◽  
Efficacy And Safety ◽  
Loss Of Response ◽  
Term Efficacy ◽  
Steroid Dependent ◽  
Inflammatory Bowel

Összefoglaló. Bevezetés: A gyulladásos bélbetegségek kezelésében a tumornekrózisfaktor-alfa-ellenes (anti-TNFα) antitestek elsődleges választási lehetőséget jelentenek a kortikoszteroid- és immunmoduláns kezelésre refrakter páciensek kezelési stratégiájában. Ezek a hatóanyagok hatékonyak, ám hosszú távú hatásosságukkal kapcsolatban sok az ellentmondás. Célkitűzés: Vizsgálatunk célja megvizsgálni az anti-TNFα-terápia (infliximab [IFX], adalimumab [ADA]) hosszú távú hatékonyságát gyulladásos bélbetegek körében. Módszerek: Retrospektív, adatgyűjtéses vizsgálatunkba a Szegedi Tudományegyetem I. Sz. Belgyógyászati Klinikáján gondozott, 18–65 év közötti gyulladásos bélbetegeket vontunk be. Az adatgyűjtést a Klinika informatikai rendszeréből végeztük a betegek ambuláns megjelenéseinek kezelőlapjaiból, illetve a zárójelentésekből. Eredmények: 102 beteg adatait elemeztük (Crohn-beteg: 67 fő, colitis ulcerosás: 35 fő). A Crohn-betegség diagnózisát követően átlagosan 7,84 év, a colitis ulcerosa diagnózisát követően átlagosan 9,86 év telt el az első anti-TNFα-terápia elkezdéséig. Az első kezelési ciklus átlagosan 2,64 évig tartott, a ciklus végén az IFX-t kapó betegek 50%-ánál, az ADA-t kapó betegek 46%-ánál volt remisszióban a betegség. A második kezelési ciklus átlagosan 4,67 évig tartott, a ciklus végén az IFX-t kapó betegek 36%-a, az ADA-t kapó betegek 40%-a volt remisszióban. Az első, illetve a második kezelési ciklus alatt az allergiás reakciók gyakorisága IFX esetében 13% és 18%, ADA esetében 4% és 3% volt. A primer hatástalanság és a másodlagos hatásvesztés az első ciklusban IFX esetében 4% és 10,5%, ADA esetében 11,5% és 19% volt. A második kezelési ciklusban IFX esetében 9%-ban és 18%-ban, ADA esetében 23%-ban és 10%-ban jelentették a ciklus végét. Következtetés: Az anti-TNFα-terápiák eredményeink alapján hosszú távon is hatékonynak és biztonságosnak bizonyultak. Másodlagos hatásvesztés kisebb arányban fordult elő a vizsgált populációban az irodalmi adatokhoz képest. Orv Hetil. 2020; 161(47): 1989–1994. Summary. Introduction: Anti-tumor necrosis factor-alpha (anti-TNFα) treatment is reserved for steroid-dependent or steroid/immunomodulator-refractory inflammatory bowel diseases patients. These agents are effective, however, their long-term safety is still questionable. Objective: We aimed to assess the long-term efficacy and safety of two anti-TNFα therapies. Methods: In our retrospective study, we reviewed medical records via the administration system of the First Department of Medicine, University of Szeged. Female and male patients, aged between 18–65 years who received anti-TNFα therapy between 2010–2019 were enrolled. Results: 102 patients with inflammatory bowel disease were enrolled (Crohn’s disease: 67, ulcerative colitis: 35). The first anti-TNFα therapy was introduced after an average 7.84 and 9.86 years from diagnosis of Crohn’s disease and ulcerative colitis. The first treatment period lasted for 2.64 years; 50% of patients receiving IFX and 46% of patients receiving ADA were in remission at the end of the period. The second treatment period lasted for 4.67 years, 36% of IFX-treated patients and 40% of ADA-treated patients were in remission at the end of the period. 13% and 18% of patients treated by IFX and 4% and 3% of patients treated by ADA experienced infusion reaction during the first and the second treatment period. Primary non-response and loss of response rates were 4% and 10.5% (IFX) and 11.5% and 19% (ADA) during the first treatment period. These rates were 9% and 18% (IFX) and 23% and 10% (ADA) during the second treatment period. Conclusion: Our study confirmed the long-term efficacy and safety of the anti-TNFα therapies. Loss of response rate is lower in our population compared to the literature. Orv Hetil. 2020; 161(47): 1989–1994.

scholarly journals Will the Inducing and Maintaining Remission of Non-biological Agents and Biological Agents Differ for Crohn's Disease? The Evidence From the Network Meta-Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Mingjun Rui ◽  
Zhengyang Fei ◽  
Yingcheng Wang ◽  
Fenghao Shi ◽  
Rui Meng ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Biological Agents ◽  
Biologic Agents ◽  
Controlled Trials ◽  
Second Line Therapy ◽  
Randomized Controlled ◽  
First Line Therapy ◽  
Line Therapy ◽  
Maintenance Of Remission

Background: Several drugs currently are available for the treatment of Crohn's disease, including non-biological agents such as anti-inflammatory agents, steroids, immunosuppressive agents, and biologic agents such as anti-tumor necrosis factor (TNF), anti-α4β7 integrin, anti-alpha-4 integrin and anti-interleukin 12/23. However, the choice of treatments for induction and maintenance is still a challenge. The relevant comparison between non-biologic agents and biologic agents is few. In our research, we aimed to help making decisions, as well as providing clinicians and patients with medication references.Methods: We searched MEDLINE, Embase, and the Cochrane Central Register of controlled trials for relevant randomized controlled trials published through to July 2020 and systematic reviews published from January 2011 to December 2020. Search results were screened by 2 independent reviewers first by title and abstract and then by full text. Disagreements were resolved through discussion with a third reviewer.Results: 54 randomized controlled trials were included in our analysis. For induction of remission, azathioprine (OR, 3.5; 95% Crl, 1.4–8.9), infliximab (OR, 4.1; 95% Crl, 1.2–16.0), infliximab + azathioprine (OR, 7.0; 95% Crl, 1.2–41.0) and infliximab+ methotrexate (OR, 7.8; 95% Crl, 1.2–65.0) were more effective in first-line therapy than placebo. Adalimumab showed superiority to placebo in second-line therapy, but the range of SD was wide. For maintenance of remission, adalimumab (OR,2.24;95% Crl,1.17–4.76) and azathioprine (OR,2.05; 95% Crl,1.14–3.96) were more effective than placebo. Adalimumab (OR,0.56; 95%Crl,0.27–1.2), budesonide (OR,0.63; 95%Crl,0.26–1.6) and natalizumab (OR,0.65; 95%Crl,0.30–1.4) was associated with less risk of withdrawals when compared with placebo.Conclusion: For induction of remission, azathioprine, infliximab, and infliximab + azathioprine were more effective in first-line therapy. In second-line therapy, adalimumab was more effective but should be interpreted carefully. For maintenance of remission, adalimumab and azathioprine were more effective. Besides, adalimumab, budesonide, natalizumab had lower withdrawals. Therefore, biological agents were not always better than non-biological agents and they have their own advantages in different treatment methods of Crohn's disease.

scholarly journals P560 Clinical outcomes of vedolizumab maintenance treatment for Korean patients with inflammatory bowel disease who failed anti-TNF therapy: A KASID prospective multicenter cohort study

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S523-S524
Author(s):  
K Oh ◽  
J Kim ◽  
N Kim ◽  
H Yoon ◽  
K M Lee ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Events ◽  
Clinical Remission ◽  
Maintenance Treatment ◽  
Multivariable Analysis ◽  
Real Life ◽  
Life Effectiveness ◽  
The Real ◽  
Korean Patients

Abstract Background We investigated the real-life effectiveness and safety of vedolizumab maintenance treatment among Korean patients with Crohn’s disease (CD) or ulcerative colitis (UC) who previously failed anti-tumour necrosis factor (anti-TNF) therapy. Methods Adult patients with CD or UC who have previously failed anti-TNF therapy and received vedolizumab were prospectively enrolled from 16 hospitals in Korea. The primary outcome was clinical remission at week 54. Clinical remission was defined as a Crohn’s disease activity index (CDAI) <150 and a partial Mayo score ≤2 with a combined rectal bleeding and stool frequency subscore ≤1. We also analyzed factors associated with clinical remission at week 54. Results Between August 2017 to July 2020, a total of 165 patients (81 with CD and 84 with UC) received vedolizumab therapy, of whom 154 patients (93.3%) (75 with CD and 79 with UC) received vedolizumab maintenance therapy (Table 1). Clinical remission and response rates at week 54 were 22.2% and 24.1% among patients with CD and 41.4% and 45.7% among patients with UC, respectively (Figure 1A and 1B). Among 70 patients with UC with baseline Mayo endoscopic subscore ≥2, endoscopic remission (Mayo endoscopic subscore ≤1) at week 54 was observed in 19 patients (27.1%). Out of 50 patients with CD with ulcers in baseline endoscopy, 2 patients (4%) showed a disappearance of ulcers at week 54 (Figure 1C). In the multivariable analysis, age at baseline (adjusted odds ration [aOR] 1.065, 95% confidence interval [CI] 1.003–1.131, P=0.041) and Mayo endoscopic subscore at baseline (aOR 0.141, 95% CI 0.026–0.746, P=0.021) were significantly associated with clinical remission at week 54 among patients with UC (Table 2). No factors were found to be associated with clinical remission at week 54 among patients with CD. Among patients who experienced one or more adverse events (n=134, 81.2%), serious adverse events occurred in 82 patients (49.7%) (Table 3). Disease exacerbation was the most common adverse events (n=89, 53.9%). Conclusion The real-life effectiveness of vedolizumab maintenance treatment for Korean patients with UC who failed anti-TNF therapy was generally similar with the outcomes reported from the previous Western studies. A substantial proportion of patients with CD experienced a loss of response during the first year of treatment. Less severe disease at baseline was associated with clinical remission at 1 year of vedolizumab therapy among patients with UC.

scholarly journals Clinical effectiveness and cost-effectiveness of elemental nutrition for the maintenance of remission in Crohn’s disease: a systematic review and meta-analysis

2015 ◽  
Vol 19 (26) ◽  
pp. 1-138 ◽  
Author(s):  
Alexander Tsertsvadze ◽  
Tara Gurung ◽  
Rachel Court ◽  
Aileen Clarke ◽  
Paul Sutcliffe
Keyword(s):  
Systematic Review ◽  
Crohn’S Disease ◽  
Cost Effectiveness ◽  
Crohn's Disease ◽  
Enteral Nutrition ◽  
Adverse Events ◽  
Clinical Effectiveness ◽  
Publication Date ◽  
Low Grade ◽  
Maintenance Of Remission

BackgroundAlthough enteral nutrition has been shown to be a viable treatment option for the management of active Crohn’s disease (CD), the evidence regarding its clinical benefits compared with standard treatments (e.g. steroids) for maintaining remission in patients with CD has been inconsistent. If enteral nutrition was to be effective, the use of drugs such as steroids and immunosuppressive drugs could be reduced, thereby reducing the likelihood of adverse events associated with these medications.ObjectivesThis systematic review aimed to assess the clinical effectiveness and cost-effectiveness of elemental nutrition (a type of enteral nutrition) for maintenance of remission in patients with CD.Data sourcesMajor bibliographic databases (e.g. MEDLINE, EMBASE, Cochrane Database of Systematic Reviews) were searched from inception to August/September 2013. Searches were not limited by study design, language or publication date. Websites for relevant organisations and references of included studies were checked.MethodsExperimental randomised and non-randomised controlled trials (RCTs and nRCTs) reporting clinical effectiveness and cost-effectiveness of elemental nutrition in the maintenance of remission in patients with CD were eligible. Study selection, data extraction and risk of bias (RoB) assessment were performed independently. Risk ratios (RRs) and mean differences (MDs) were pooled using a random-effects model. Heterogeneity was assessed via forest plots, Cochran’sQand theI2statistics. Overall, quality of evidence for each outcome was rated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.ResultsEight studies (three RCTs and five nRCTs) were included in the review. RCTs indicated a significant benefit of elemental nutrition vs. no intervention (an unrestricted diet) in maintaining remission at 24 months [one RCT; RR 2.06, 95% confidence interval (CI) 1.00 to 4.43; very low-grade evidence] and preventing relapse at 12–24 months post baseline (two RCTs; pooled RR 0.57, 95% CI 0.38 to 0.84;I2 = 0%; high-grade evidence). Similarly, three nRCTs showed significant benefits of elemental nutrition over no intervention in maintaining remission at 12–48 months and preventing relapse at 12 months post baseline (MD 1.20 months, 95% CI 0.35 to 2.04 months). The incidence of mucosal healing was not significantly different in the intervention and control groups (RR 2.70, 95% CI 0.62 to 11.72). Adherence to an elemental nutrition regime was significantly worse than adherence to polymeric nutrition (RR 0.68, 95% CI 0.50 to 0.92) and, when compared with other active treatments (medications, polymeric nutrition or a combination), elemental nutrition yielded non-significant results with wide 95% CIs, rendering these results inconclusive. Complications and adverse events were too sparse to allow meaningful comparisons. None of the studies reported cost-effectiveness of elemental nutrition. Owing to scarcity of data, subgroup and sensitivity analyses could not be performed to explore methodological and clinical sources of heterogeneity.LimitationsThe findings warrant cautious interpretation given the limitations of the evidence in methodological quality (small samples, short follow-up) and the RoB in individual studies (lack of blinding, confounding).ConclusionsLimited evidence indicates potential benefits of elemental nutrition against no intervention in the maintenance of remission and prevention of relapse in adult patients with CD. There was a lack or insufficient evidence on adverse events and complications. Future large and long-term randomised trials are warranted to draw more definitive conclusions regarding the effects of elemental nutrition in maintaining remission in CD.Trial registrationThis study is registered as PROSPERO CRD42013005134.FundingThe National Institute for Health Research Health Technology Assessment programme.

Safety of switching systemic steroids to budesonide modified-release capsules in steroid-dependent patients with inactive Crohn's disease

2001 ◽  
Vol 120 (5) ◽  
pp. A749-A749
Author(s):  
A CORTOT ◽  
J COLOMBEL ◽  
P RUTGEERTS ◽  
K LAURITSEN ◽  
H MALCHOW ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Modified Release ◽  
Systemic Steroids ◽  
Steroid Dependent
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