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Current Gastroenterology Reports Nov 2023This review focuses on recent advancements in anti-TNF therapeutic drug monitoring (TDM), pharmacogenetics and personalized drug selection for children with inflammatory... (Review)
Review
PURPOSE OF THE REVIEW
This review focuses on recent advancements in anti-TNF therapeutic drug monitoring (TDM), pharmacogenetics and personalized drug selection for children with inflammatory bowel disease (IBD).
RECENT FINDINGS
Several real-world studies and one clinical trial in children have demonstrated that proactive TDM, targeting higher exposure concentrations (> 5 µg/mL), can improve disease remission rates and enhance durability of the anti-TNF biologics. Recent data from both adult and pediatric IBD patients have revealed an association between a genetic polymorphism (HLA-DQA1*05) and the development of auto-drug antibodies. The impact of this association on clinical outcomes, considering more routine use proactive TDM and dose optimization in children, is still under investigation. Additionally, recent studies have identified potential inflammatory signatures and biomarkers that may serve as companion diagnostics for anti-TNF biologics. The effective management of anti-TNF therapies in children with IBD requires evidence-based precision dosing strategies, including routine TDM and proactive pharmacodynamic assessments.
Topics: Adult; Humans; Child; Tumor Necrosis Factor Inhibitors; Gastrointestinal Agents; Tumor Necrosis Factor-alpha; Inflammatory Bowel Diseases; Biological Products; Drug Monitoring; Infliximab
PubMed: 37695555
DOI: 10.1007/s11894-023-00895-4 -
Cells Feb 2021The effect of switching from originator infliximab to biosimilar infliximab in patients with sarcoidosis is unknown. The objective of this study is to investigate the... (Review)
Review
The effect of switching from originator infliximab to biosimilar infliximab in patients with sarcoidosis is unknown. The objective of this study is to investigate the effect of switching from Remicade or Inflectra to Flixabi in patients with severe refractory sarcoidosis. This single center retrospective cohort study was performed at St Antonius Hospital Nieuwegein, The Netherlands. All patients diagnosed with severe refractory sarcoidosis receiving Remicade or Inflectra switched to Flixabi. The primary outcome was infliximab discontinuation within 6 months of switching. Secondary endpoints included adverse events and loss of clinical, functional, or inflammatory response. Out of 86 patients who switched to Flixabi, 79 patients had complete data. None of the 79 patients discontinued infliximab during the first 6 months after switching. Five patients reported an adverse event related to Flixabi treatment. We found no change from baseline in FVC, FEV1, DLCOc, 6MWT, and infliximab trough levels 26 weeks after switching. An improvement in physical functioning of 7.3 ± 13.4 points ( = 0.002) with RAND/SF36 and in biomarker sIL-2R (-475.58 ± 1452.39; = 0.005) was observed. Switching from originator infliximab Remicade or biosimilar infliximab Inflectra to biosimilar infliximab Flixabi did not result in treatment discontinuation or loss of clinical/functional/inflammatory remission.
Topics: Antirheumatic Agents; Humans; Infliximab; Sarcoidosis; Sweden; Treatment Outcome
PubMed: 33669641
DOI: 10.3390/cells10020441 -
Journal of Clinical Gastroenterology Feb 2017The incidence of inflammatory bowel disease (IBD) has increased steadily worldwide, both in adult and in children; approximately 25% of IBD patients are diagnosed before... (Review)
Review
The incidence of inflammatory bowel disease (IBD) has increased steadily worldwide, both in adult and in children; approximately 25% of IBD patients are diagnosed before the age of 18. The natural history of IBD is usually more severe in children than in adults, and can be associated with linear growth impairment, delayed puberty onset, reduced bone mass index, malnutrition, and the need for surgery. Biological therapies, especially blocking tumor necrosis factor-α (TNFα), have radically modified the treatment strategies and disease course of IBD in children. In particular, drugs such as Infliximab and Adalimumab are routinely used in the treatment of pediatric IBD. The role of Infliximab and Adalimumab in the management of pediatric IBD has been recently updated in the Consensus guidelines of ECCO/ESPGHAN. Data regarding short-term and long-term efficacy and safety of these drugs in children, and the effects of "top-down" and "step-up" strategies, are lacking. In this paper, the authors will review current indications, efficacy, and safety of biological therapy in pediatric IBD patients, evaluating all articles published after ECCO/ESPGHAN guidelines publication. The authors carried out a systematic search through MEDLINE through PubMed (http://www.ncbi.nlm.nih.gov/pubmed/) Embase, CINAHL, Cochrane Library, and gray literature, from January 2013 to January 2016. Anti-TNFα has been shown to be effective and safe to maintain remission and to achieve mucosal healing. Multicenter trials based on large sample size cohorts are needed to better clarify long-term efficacy of anti-TNFα and the real incidence of treatment-related complications in pediatric IBD.
Topics: Adalimumab; Adolescent; Anti-Inflammatory Agents; Biological Products; Child; Humans; Inflammatory Bowel Diseases; Infliximab; Practice Guidelines as Topic; Treatment Outcome
PubMed: 27636407
DOI: 10.1097/MCG.0000000000000696 -
Journal For Immunotherapy of Cancer Nov 2021Current treatment guidelines for immune-mediated diarrhea and colitis (IMDC) recommend steroids as first-line therapy, followed by selective immunosuppressive therapy...
BACKGROUND
Current treatment guidelines for immune-mediated diarrhea and colitis (IMDC) recommend steroids as first-line therapy, followed by selective immunosuppressive therapy (SIT) (infliximab or vedolizumab) for refractory cases. We aimed to compare the efficacy of these two SITs and their impact on cancer outcomes.
METHODS
We performed a two-center, retrospective observational cohort study of patients with IMDC who received SITs following steroids from 2016 to 2020. Patients' demographic, clinical, and overall survival data were collected and analyzed.
RESULTS
A total of 184 patients (62 vedolizumab, 94 infliximab, 28 combined sequentially) were included. The efficacy of achieving clinical remission of IMDC was similar (89% vs 88%, p=0.79) between the two groups. Compared with the infliximab group, the vedolizumab group had a shorter steroid exposure (35 vs 50 days, p<0.001), fewer hospitalizations (16% vs 28%, p=0.005), and a shorter hospital stay (median 10.5 vs 13.5 days, p=0.043), but a longer time to clinical response (17.5 vs 13 days, p=0.012). Longer durations of immune checkpoint inhibitors treatment (OR 1.01, p=0.004) and steroid use (OR 1.02, p=0.043), and infliximab use alone (OR 2.51, p=0.039) were associated with higher IMDC recurrence. Furthermore, ≥3 doses of SIT (p=0.011), and fewer steroid tapering attempts (p=0.012) were associated with favorable overall survival.
CONCLUSIONS
Treatment with vedolizumab as compared with infliximab for IMDC led to comparable IMDC response rates, shorter duration of steroid use, fewer hospitalizations, and lower IMDC recurrence, though with slightly longer time to IMDC response. Higher number of SIT doses was associated with better survival outcome, while more steroid exposure resulted in worse patient outcomes.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Colitis; Diarrhea; Female; Humans; Infliximab; Male; Middle Aged; Neoplasms
PubMed: 34789551
DOI: 10.1136/jitc-2021-003277 -
BioDrugs : Clinical Immunotherapeutics,... Feb 2017Biological therapies represent a fundamental innovation for the management of inflammatory bowel diseases (IBD). However, many biological originators have reached, or... (Review)
Review
BACKGROUND
Biological therapies represent a fundamental innovation for the management of inflammatory bowel diseases (IBD). However, many biological originators have reached, or are about to reach, patent expiry and long-term therapy costs have become progressively unsustainable. CT-P13, a biosimilar of the anti-tumor necrosis factor (anti-TNF) monoclonal antibody infliximab, might represent a significant alternative to its originator, with the potential to decrease medical care costs and, therefore, become available to a large number of patients.
OBJECTIVES
In this systematic review, we analyzed the data from available clinical trials that recently investigated the validity of indication extrapolation of CT-P13 for the treatment of IBD in naïve patients and in patients who switched from its originator infliximab, focusing on clinical efficacy, safety and immunogenicity.
METHODS
A detailed literature search was developed a priori to identify articles that investigated the validity of indication extrapolation of CT-P13 for the treatment of IBD in TNF inhibitor treatment-naïve patients and in patients who switched from the originator infliximab. This was applied to Ovid MEDLINE, In-Process and Other Non-Indexed Citations, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus for content from 2012 to September 2016.
RESULTS
We based our review on the available data from 11 studies that included a total of 1007 IBD patients: 570 patients suffering from Crohn's disease (294 switched and 276 naïve), 435 patients suffering from ulcerative colitis (127 switched and 308 naïve), and two IBD unclassified patients (switched). Overall, no significant difference in efficacy and safety between the originator infliximab and its biosimilar CT-P13 was observed. When assessing the safety of CT-P13, we found that 9.2% of patients experienced adverse effects (4.1% infusion-related reactions and 4.3% infections).
CONCLUSION
The analyzed studies did not report a significant difference in terms of efficacy, safety and immunogenicity when comparing the clinical experience with CT-P13 with the available literature data on the originator treatment in IBD. However, some debate is ongoing regarding interchangeability and immunogenicity.
Topics: Animals; Antibodies, Monoclonal; Biosimilar Pharmaceuticals; Humans; Inflammatory Bowel Diseases; Infliximab; Retrospective Studies; Treatment Outcome
PubMed: 28035633
DOI: 10.1007/s40259-016-0206-1 -
Gastroenterology Clinics of North... Sep 2023The use of biologic therapies has changed the treatment landscape for children with inflammatory bowel disease. While the novel biologics have improved clinical... (Review)
Review
The use of biologic therapies has changed the treatment landscape for children with inflammatory bowel disease. While the novel biologics have improved clinical outcomes, there remains a significant gap in achieving endoscopic remission, prolonged steroid-free remission, and drug durability. Contributing to this gap is the paucity of real-world pharmacokinetic studies in children and a failure to dose optimize therapy during induction. Emerging data from a pediatric clinical trial and several observational studies have shown that the combination of proactive therapeutic drug monitoring and achievement of early therapeutic concentrations is effective in achieving improved outcomes. The next steps will be to leverage these past studies to develop more innovative clinical trials to properly assess the safety and effectiveness of proactive therapeutic drug monitoring in children.
Topics: Humans; Child; Drug Monitoring; Inflammatory Bowel Diseases; Treatment Outcome; Remission Induction; Biological Products; Gastrointestinal Agents; Infliximab
PubMed: 37543399
DOI: 10.1016/j.gtc.2023.05.002 -
Journal of Translational Medicine Mar 2024Inflammatory bowel disease (IBD) is a chronic gastrointestinal condition characterized by severe gut inflammation, commonly presenting as Crohn's disease, ulcerative... (Review)
Review
Inflammatory bowel disease (IBD) is a chronic gastrointestinal condition characterized by severe gut inflammation, commonly presenting as Crohn's disease, ulcerative colitis or categorized as IBD- unclassified. While various treatments have demonstrated efficacy in adult IBD patients, the advent of anti-TNF therapies has significantly revolutionized treatment outcomes and clinical management. These therapies have played a pivotal role in achieving clinical and endoscopic remission, promoting mucosal healing, averting disease progression, and diminishing the necessity for surgery. Nevertheless, not all patients exhibit positive responses to these therapies, and some may experience a loss of responsiveness over time. This review aims to present a comprehensive examination of predictive biomarkers for monitoring the therapeutic response to anti-TNF therapy in IBD patients. It will explore their limitations and clinical utilities, paving the way for a more personalized and effective therapeutic approach.
Topics: Adult; Humans; Infliximab; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Inflammatory Bowel Diseases; Colitis, Ulcerative; Biomarkers
PubMed: 38493113
DOI: 10.1186/s12967-024-05058-1 -
Journal of Clinical Pharmacology Feb 2021Treatment of patients with biologics such as infliximab may trigger development of antidrug antibodies, which are associated with faster drug clearance, reduced... (Randomized Controlled Trial)
Randomized Controlled Trial
Treatment of patients with biologics such as infliximab may trigger development of antidrug antibodies, which are associated with faster drug clearance, reduced treatment efficacy, and increased risk of infusion-related reactions. The aim of this study was to identify predictors of baseline infliximab clearance and early antidrug antibody formation. Pharmacokinetic and pharmacokinetic/pharmacodynamic models for infliximab were developed using 21 178 observations from 859 patients from the PLANETRA (ClinicalTrials.gov identifier: NCT01217086) and PLANETAS (NCT01220518) studies in rheumatoid arthritis and ankylosing spondylitis, respectively, to address the specified aims. Infliximab pharmacokinetics were well described by a 2-compartment model with linear mean estimated baseline clearance of 0.26 L/day. Alongside increased body weight, serum C-reactive protein, and antidrug antibody concentrations and decreased serum albumin, elevated serum glucose levels predicted higher clearance. In patients with rheumatoid arthritis, baseline infliximab clearance and body weight were the only identified predictors of early antidrug antibody detection. The odds ratio for antidrug antibody detection for each 0.1 L/day increase in baseline infliximab clearance was 1.78 (95% confidence interval, 1.50-2.12); for each 10-kg increase in body weight, this was 1.19 (1.06-1.33). Here we describe increased serum glucose levels as a novel independent predictor of baseline infliximab clearance. Estimates of baseline infliximab clearance should be incorporated to guide dosing modifications and/or antidrug antibody prophylaxis in clinical practice.
Topics: Adolescent; Adult; Aged; Antirheumatic Agents; Arthritis, Rheumatoid; Blood Glucose; Body Weight; C-Reactive Protein; Double-Blind Method; Female; Humans; Infliximab; Male; Metabolic Clearance Rate; Middle Aged; Serum Albumin; Spondylitis, Ankylosing; Young Adult
PubMed: 32905628
DOI: 10.1002/jcph.1732 -
BMJ Case Reports Oct 2021A 70-year-old man was referred to our respiratory department with non-productive cough over the past 6 months. High-resolution CT revealed reticular pattern with basal...
A 70-year-old man was referred to our respiratory department with non-productive cough over the past 6 months. High-resolution CT revealed reticular pattern with basal and peripheral predominance, centrilobular nodules and mild ground glass opacities. Serology tests were normal and bronchoalveolar lavage revealed lymphocytosis. Pulmonary function tests showed functional impairment and reduced diffusing capacity for carbon monoxide. Meticulous evaluation of patient's medical history unveiled longitudinal administration of infliximab due to diagnosis of psoriasis. The working diagnosis of drug-induced interstitial lung disease was proposed following multidisciplinary discussion. Considerable radiological and functional improvement was determined 6 months following infliximab discontinuation without implementation of corticosteroids. To this end, the patient has reported remission of cough and functional improvement.
Topics: Aged; Bronchoalveolar Lavage; Humans; Infliximab; Lung; Lung Diseases, Interstitial; Male; Respiratory Function Tests; Tomography, X-Ray Computed
PubMed: 34645638
DOI: 10.1136/bcr-2021-245726 -
Psychoneuroendocrinology Dec 2018The tumor necrosis factor (TNF) antagonist infliximab was previously found to reduce depressive symptoms in patients with treatment-resistant major depression (TRD) who...
The tumor necrosis factor (TNF) antagonist infliximab was previously found to reduce depressive symptoms in patients with treatment-resistant major depression (TRD) who exhibited high baseline inflammation, as reflected by plasma C-reactive protein (CRP) >5 mg/L. Further predictors of antidepressant response to infliximab included differential expression of peripheral blood gene transcripts that were related not only to inflammation but also to glucose and lipid metabolism. To determine whether plasma biomarkers of glucose and lipid metabolism were similarly associated with antidepressant response to infliximab and with relevant gene transcripts, we measured concentrations of glucose, insulin, and protein hormones that regulate glucose homeostasis and metabolism (leptin, resistin, and adiponectin), as well as cholesterols, triglycerides, and non-esterified fatty acids (NEFA), in medically-stable TRD outpatients at baseline and 2 weeks after the first infusion of infliximab (n = 26) or placebo (n = 26). Treatment response was defined as 50% reduction in depressive symptoms at any point during the 12-week trial. We found that baseline cholesterol (total, low-density lipoprotein [LDL], and non-high-density lipoprotein [non-HDL]), triglycerides and NEFA were elevated in patients who exhibited an antidepressant response to infliximab (all p < 0.05) but not placebo (all p > 0.299). HDL and non-HDL cholesterol concentrations also correlated with two lipid-related gene transcripts that were predictive of antidepressant response (r = 0.33 to 0.39, p < 0.05). Although not associated with response to infliximab, resistin correlated with numerous glucose-related transcripts (r = -0.32 to 0.37, p < 0.05) and was higher at 2 weeks post-infusion in patients treated with infliximab compared to placebo (p = 0.028). Concentrations of cholesterol (total, LDL, HDL, non-HDL) were also lower at 2 weeks in patients treated with infliximab compared to placebo, but only in those patients with CRP >5 mg/L at baseline (all p < 0.05). These results are consistent with previous work showing that high inflammation in patients with depression is associated with metabolic alterations, which together predict response to both traditional and experimental antidepressant therapies. Additionally, our findings suggest a causal relationship between increased inflammation and high cholesterol in depression, as a single infusion of infliximab reduced cholesterol in TRD patients with high CRP compared to placebo.
Topics: Adult; Antidepressive Agents; Biomarkers, Pharmacological; C-Reactive Protein; Cholesterol; Depression; Depressive Disorder, Treatment-Resistant; Fatty Acids, Nonesterified; Female; Glucose; Humans; Inflammation; Infliximab; Lipid Metabolism; Male; Middle Aged; Triglycerides; Tumor Necrosis Factor-alpha
PubMed: 30249443
DOI: 10.1016/j.psyneuen.2018.09.004