Predictive factors of response to infliximab therapy in Brazilian inflammatory bowel disease patients
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PROVIDER: S-EPMC10652804 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundNo models predict future outcomes in inflammatory bowel disease (IBD) patients receiving maintenance infliximab therapy. We created a predictive model for unfavorable outcomes.MethodsAdult patients with IBD receiving maintenance infliximab therapy at 2 centers with matched serum infliximab concentrations and blinded histologic scores (Robarts Histopathologic Index [RHI]) were included. The primary endpoint was an unfavorable outcome of active objective inflammation or need for IBD-related surgery or hospitalization at 6-18 months follow-up. Internal variables were identified using univariable analyses, modeling used multivariable analysis, and performance was assessed (area under receiver-operating curve [AUC]) and externally validated.ResultsIn 81 patients, 40.7% developed unfavorable outcomes at follow-up. Infliximab concentration <9.3 µg/mL (odds ratio [OR] 5.3, P = .001) and RHI > 12 (OR 3.4, P = .03) were the only factors associated with developing the primary unfavorable outcome. A prediction score assigning 1 point to each variable had good discrimination and performed similarly on internal (AUC 0.71) and external (AUC 0.73) cohorts. The risk of primary unfavorable outcomes in internal and external cohorts, respectively, was 23% and 15% for a score of 0, 46% and 50% for a score of 1, and 100% and 75% for a score of 2. Infliximab concentration alone performed similar to the 2-predictor model in internal (AUC 0.65, P = .5 vs. 2-predictor model) and external (AUC 0.70, P = .9, vs. 2-predictor model) cohorts.ConclusionsUsing unbiased variable selection, a 2-predictor model using infliximab concentrations and histology identified IBD patients on maintenance infliximab therapy at high risk of future unfavorable outcomes. For practical applicability, infliximab concentrations alone performed similarly well.
| S-EPMC11645457 | biostudies-literature
Project description:Infliximab is commonly used in inflammatory bowel disease (IBD), however, differences in clinical response among patients are common. Several studies have considered the possibility that these differences are caused by genetic variability even if no unique marker has been yet identified in pediatric patients. We evaluated the impact of two candidate single-nucleotide polymorphisms (SNPs) rs396991 in FCGR3A and rs1800629 in TNFα genes on infliximab response in an Italian cohort of 76 pediatric patients with IBD. Results showed that patients with the variant FCGR3A allele had a reduced clinical response at the end of induction (p value = 0.004), at 22 weeks (p value = 0.001), and at 52 weeks of treatment (p value = 0.01). A significant association between the FCGR3A variant and median infliximab levels measured during maintenance therapy was also observed: patients with wild type genotype had higher infliximab levels compared to patient with variant allele. Furthermore, patients with the variant allele had a higher probability to produce antidrug antibodies (ADAs). No association was found among the TNFα SNP, clinical response, and infliximab levels. This study addressed for the first time in pediatric patients with IBD, the association of FCGR3A SNP, infliximab response, and ADA production.
| S-EPMC8604212 | biostudies-literature
Project description:ObjectivesTo evaluate the efficiency and the predictive factors of clinical response of infliximab in active nonradiographic axial spondyloarthritis patients.MethodsActive nonradiographic patients fulfilling ESSG criteria for SpA but not fulfilling modified New York criteria were included. All patients received infliximab treatment for 24 weeks. The primary endpoint was ASAS20 response at weeks 12 and 24. The abilities of baseline parameters and response at week 2 to predict ASAS20 response at weeks 12 and 24 were assessed using ROC curve and logistic regression analysis, respectively.ResultsOf 70 axial SpA patients included, the proportions of patients achieving an ASAS20 response at weeks 2, 6, 12, and 24 were 85.7%, 88.6%, 87.1%, and 84.3%, respectively. Baseline MRI sacroiliitis score (AUC = 0.791; P = 0.005), CRP (AUC = 0.75; P = 0.017), and ASDAS (AUC = 0.778, P = 0.007) significantly predicted ASAS20 response at week 12. However, only ASDAS (AUC = 0.696, P = 0.040) significantly predicted ASAS20 response at week 24. Achievement of ASAS20 response after the first infliximab infusion was a significant predictor of subsequent ASAS20 response at weeks 12 and 24 (wald χ(2) = 6.87, P = 0.009, and wald χ(2) = 5.171, P = 0.023).ConclusionsInfliximab shows efficiency in active nonradiographic axial spondyloarthritis patients. ASDAS score and first-dose response could help predicting clinical efficacy of infliximab therapy in these patients.
| S-EPMC4529933 | biostudies-literature
Project description:Tenascin-C (TNC) is an extracellular matrix glycoprotein expressed in response to inflammation and tissue damage. The role of TNC in patients with inflammatory bowel disease (IBD) is not well understood. In this study, we analyzed the expression of TNC in the inflamed mucosa of patients with ulcerative colitis (UC) and Crohn's disease (CD). Serum TNC levels were determined by the enzyme-linked immunosorbent assay (ELISA), and the levels of TNC in patients with different disease activities were compared. The expression of TNC was derived from a GEO dataset. THP-1 cells were stimulated with TNC to evaluate the proinflammatory role of TNC. We found higher TNC expression in the inflamed mucosa of patients with UC and CD compared with normal controls (NCs). TNC was mainly expressed in the stromal area of the intestinal mucosa. The median serum levels of TNC were significantly higher in UC (median 74.1 ng/ml, range 42.6-102.1 ng/ml) and CD (median 59.2 ng/ml, range 44.0-80.9 ng/ml). We also found that serum TNC levels were correlated with Mayo scores in UC and Crohn's disease activity index (CDAI) in CD. Through GSE14580, we demonstrated that patients who were nonresponsive to infliximab treatment had higher mucosal TNC mRNA expression. High TNC mRNA expression in the inflamed intestinal mucosa was associated with poor response to infliximab therapy in patients with UC. Furthermore, THP-1 cells stimulated with TNC showed increased expression of IL-6, but not TNF-α, IL-8, MCP-1, or IL-1β. Thus, increased TNC levels may participate in the pathogenesis of IBD and may serve as a biomarker for disease activity and response to treatment with infliximab.
| S-EPMC6893280 | biostudies-literature
Project description:Background and aimFatigue is a common and bothersome symptom in inflammatory bowel disease (IBD) patients. The study was aimed to determine the relationship of biological and psychological factors with IBD-related fatigue.MethodsConsecutive clinically inactive IBD outpatients receiving immunosuppressants or biological drugs were enrolled between January and December 2013. Patients completed a Fatigue score (FACIT-F), various psychological, quality of life (IBDQ-9), and IBD activity scores. Biological parameters were assessed, including levels of interleukins (IL-5, IL-8 and IL-12) and micronutrients.ResultsWe prospectively recruited 202 patients (28% ulcerative colitis and 72% Crohn's disease) for the study. Fatigue measured by FACIT-F score was prevalent in the studied population (54%, 96/177) and higher than in the general population. In the univariate analysis no relation was found between IL levels or micronutrient deficiencies and fatigue. Fatigue was significantly related to female sex, Crohn's disease, joint disorders, body mass index (BMI), psychological tests, thiopurine use, and anti-TNF treatment. All these variables were included in the multivariate analysis. Female sex (OR: 4.8), high BMI (OR:1.2) and higher depression rates (OR:1.2) were predictors of increased fatigue. High IBDQ-9 score (OR: 0.82) was significantly related to lower degrees of fatigue.ConclusionFatigue was prevalent in quiescent IBD patients with moderate-to-severe disease. It was associated with high levels of depression, low quality of life, and female sex. No association was found with the other biological and psychological factors evaluated.
| S-EPMC5531543 | biostudies-literature
Project description:BackgroundInadequate infliximab (IFX) drug exposure remains a clinical challenge and leads to high loss of response rates and therapy failure in inflammatory bowel disease (IBD). We aimed to determine the feasibility and pilot effectiveness of a novel, web-based, mobile IFX dosing calculator (mIDC) for therapy optimization.MethodsWe developed an mIDC leveraging the known clinical variables of C-reative protein (CRP), albumin, patient's weight, disease activity indices, calprotectin, drug trough levels, and antibodies to IFX that significantly affect pharmacokinetics and/or outcomes. A prospective observational cohort study in pediatric and young adult IBD patients receiving maintenance IFX was performed. System-wide practice adoption of mIDC was achieved through a quality improvement (QI) initiative within a hospital-based infusion unit.ResultsForty-nine patients (median age: 16.0 years; 55% female; 65% Crohn's disease) were followed over 9 months. mIDC recommendations for dose optimization were followed by the treating physicians in 198 (89%) out of 222 infusions. Twenty-eight (13%) of 222 mIDC recommendations were to escalate IFX dosing; 15 (54%) of 28 escalation recommendations were declined, and these patients were more likely to already be receiving IFX dose intensification compared with those in whom escalation recommendations were followed (P < 0.05). From mIDC initiation to end of follow-up, mean albumin levels remained unchanged at 3.8 g/dL. Median CRP remained unchanged at 2 g/L. Median calprotectin levels showed a downward trend from 30 to 27 μg/g (n = 9, P < 0.05). The percentage of patients undergoing therapeutic drug monitoring in clinical care increased from 34% to 86% with the QI initiative. The target median IFX trough goal of >5 μg/mL was achieved with 81% probability throughout the QI initiative, an increase of 12% compared with pre-QI values.ConclusionsThe use of a novel mIDC is feasible and potentially effective, facilitating both standardization and individualization of therapy in clinical care. mIDC appears to be a practical IFX dosing tool for point-of-care use, leveraging individual pharmacokinetic considerations.
| S-EPMC6048868 | biostudies-literature
Project description:ObjectiveInvestigate the association between infliximab trough levels and quality of life in inflammatory bowel disease patients in maintenance therapy.MethodsWe carried out a transversal study with inflammatory bowel disease patients in infliximab maintenance therapy. Infliximab trough levels were determined using a quantitative rapid test. Disease activity indices (partial Mayo Score and Harvey-Bradshaw Index) and endoscopic scores (endoscopic Mayo Score or Simple Endoscopic Score in Crohn's disease) were obtained. Quality of life was assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ).ResultsSeventy-one consecutive subjects were included in the study (55 with Crohn's disease and 16 with ulcerative colitis). Drug levels were considered satisfactory (≥3 μg/mL) in 28 patients (39.4%) and unsatisfactory (<3 μg/mL) in 43 (60.6%). Satisfactory trough levels were associated with higher rates of clinical remission and mucosal healing. Higher trough levels were also associated with improved IBDQ scores, particularly regarding bowel symptoms, systemic function, and social function.ConclusionSatisfactory trough levels of infliximab were associated with higher rates of clinical remission, mucosal healing, and improved quality of life in inflammatory bowel disease patients on maintenance therapy.
| S-EPMC5964568 | biostudies-literature
Project description:BackgroundOne-third of inflammatory bowel disease (IBD) patients show no response to infliximab (IFX) induction therapy, and approximately half of patients responding become unresponsive over time. Thus, identification of potential treatment response biomarkers are of great clinical significance. This study employs spectroscopy-based metabolic profiling of serum from patients with IBD treated with IFX and healthy subjects (1) to substantiate the use of spectroscopy as a semi-invasive diagnostic tool, (2) to identify potential biomarkers of treatment response and (3) to characterise the metabolic changes during management of patients with tumour necrosis factor-α inhibitors.MethodsSuccessive serum samples collected during IFX induction treatment (weeks 0, 2, 6 and 14) from 87 IBD patients and 37 controls were analysed by 1H nuclear magnetic resonance (NMR) spectroscopy. Data were analysed with principal components analysis and orthogonal projection to latent structures discriminant analysis using SIMCA-P+ v12 and MATLAB.ResultsMetabolic profiles were significantly different between active ulcerative colitis and controls, active Crohn's disease and controls, and quiescent Crohn's disease and controls. Metabolites holding differential power belonged primarily to lipids and phospholipids with proatherogenic characteristics and metabolites in the pyruvate metabolism, suggestive of an intense inflammation-driven energy demand. IBD patients not responding to IFX were identified as a potentially distinct group based on their metabolic profile, although no applicable response biomarkers could be singled out in the current setting.Conclusion1H NMR spectroscopy of serum samples is a powerful semi-invasive diagnostic tool in flaring IBD. With its use, we provide unique insights into the metabolic changes taking place during induction treatment with IFX. Of distinct clinical relevance is the identification of a reversible proatherogenic lipid profile in IBD patients with active disease, which partially explains the increased risk of cardiovascular disease associated with IBD.
| S-EPMC5641999 | biostudies-literature
Project description:Vaccination is a promising strategy to protect vulnerable groups like inflammatory bowel disease (IBD) patients against COVID-19 and associated severe outcomes. COVID-19 vaccine clinical trials excluded IBD patients taking infliximab with azathioprine or 6-mercaptopurine (infliximab combination). Therefore, we sought to evaluate serologic responses to COVID-19 vaccination with the mRNA vaccine, BNT162b2, in patients with IBD receiving infliximab combination therapy compared with healthy participants. This was a multicenter prospective study. Patients with IBD were recruited at the time of attendance at infusion center between 1 August 2021, and 15 September 2021. Our primary outcome were the concentrations of SARS-CoV-2 antibodies 4-10 weeks after vaccination with two doses of BNT162b2 vaccine in patients with IBD taking infliximab combination therapy (study group) compared with a healthy participants group (control group). Both study and control groups were matched for age, sex, and time-since-last-vaccine-dose using optimal pair-matching method. In total, 116 participants were recruited in the study, 58 patients in the study group and 58 in the control group. Median (IQR) IgG concentrations were lower in the study group (99 BAU/mL (40, 177)) than the control group (139 BAU/mL (120, 188)) following vaccination (p = 0.0032). Neutralizing antibodies were also lower in the study group compared with the control group (64% (23, 94) vs. 91% (85, 94), p < 0.001). The median IgA levels in the study group were also significantly lower when compared with the control group (6 U/mL (3, 34) vs. 13 U/mL (7, 30), p = 0.0097). In the study group, the percentages of patients who achieved positive IgG, neutralizing antibody and IgA levels were 81%, 75%, and 40%, respectively. In the control group, all participants (100%) had positive IgG and neutralizing antibody levels while 62% had positive IgA levels. In patients with IBD receiving infliximab combination therapy, SARS-CoV2 IgG, IgA, and neutralizing antibody levels after BNT162b2 vaccination were lower compared with healthy participants. However, most patients treated with infliximab combination therapy seroconverted after two doses of the vaccine.
| S-EPMC8623980 | biostudies-literature
Project description:Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammation of the gastrointestinal tract with a highly heterogeneous presentation. It has a relapsing and remitting clinical course that necessitates lifelong monitoring and treatment. Although the availability of a variety of effective therapeutic options including immunomodulators and biologics (such as TNF, CAM inhibitors) has led to a paradigm shift in the treatment outcomes and clinical management of IBD patients, some patients still either fail to respond or lose their responsiveness to therapy over time. Therefore, according to the recent Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) recommendations, continuous disease monitoring from symptomatic relief to endoscopic healing along with short- and long-term therapeutic responses are critical for providing IBD patients with a tailored therapy algorithm. Moreover, considering the high unmet need for novel therapeutic approaches for IBD patients, various new modulators of cytokine signaling events (for example, JAK/TYK inhibitors), inhibitors of cytokines (for example IL-12/IL-23, IL-22, IL-36, and IL-6 inhibitors), anti-adhesion and migration strategies (for example, β7 integrin, sphingosine 1-phosphate receptors, and stem cells), as well as microbial-based therapeutics to decolonize the bed buds (for example, fecal microbiota transplantation and bacterial inhibitors) are currently being evaluated in different phases of controlled clinical trials. This review aims to offer a comprehensive overview of available treatment options and emerging therapeutic approaches for IBD patients. Furthermore, predictive biomarkers for monitoring the therapeutic response to different IBD therapies are also discussed.
| S-EPMC9266456 | biostudies-literature