Delaying an infliximab infusion by more than 3 days is associated with a significant reduction in trough levels but not with clinical worsening
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ABSTRACT: Background:
Higher infliximab trough levels (TLs) correlate with better clinical,
SUBMITTER: Ben-Shatach Z
PROVIDER: S-EPMC9133860 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundExposure-response studies have shown that higher infliximab concentrations are associated with better outcomes in inflammatory bowel disease. There is little agreement about the optimal time to measure infliximab levels in children.ObjectivesWe aimed to evaluate whether trough levels at week 6 or week 14 predict sustained remission. The secondary aim was to define target trough levels at weeks 6 and 14.DesignWe used routinely collected electronic healthcare data of 70 anti-tumour necrosis factor naïve children with inflammatory bowel disease treated with a standard infliximab induction- and variable maintenance scheme.MethodsTrough levels and blood and faecal markers for disease activity were measured before every infliximab administration. Sustained remission was defined as the absence of symptoms and low inflammatory markers between weeks 26 and 52 after the start of infliximab therapy. Optimal infliximab levels at weeks 6 and 14 were determined using the receiver operating characteristic curve.ResultsThe median infliximab level at week 6 was not significantly higher in children who achieved sustained remission compared to those who did not (16.9 mg/L versus 12.0 mg/L; p = 0.058) but the median infliximab level at week 14 was significantly higher in those with sustained remission (7.7 mg/L versus 3.8 mg/L; p = 0.006). The area under the receiver operating characteristics curves at weeks 6 and 14 to predict sustained remission was 0.67 (95% CI 0.51-0.83) and 0.75 (95% CI 0.60-0.90), respectively. Target trough levels at weeks 6 and 14 were ⩾13.2 and ⩾6.9 mg/L, respectively.ConclusionAn infliximab measurement at week 14 with a target through level ⩾6.9 mg/L best predicted sustained remission.
| S-EPMC10757796 | biostudies-literature
Project description:Although infliximab (IFX) is an efficient therapy for ulcerative colitis (UC) patients, a considerably high rate of therapeutic failures still occurs. This study aimed at a better understanding of IFX pharmacokinetics and pharmacodynamics among clinically-asymptomatic UC patients. This was a multicentric and prospective study involving 65 UC patients in the maintenance phase of IFX therapy. There were no significant differences between patients with positive and negative clinical, endoscopic and histological outcomes concerning their IFX trough levels (TLs), area under the IFX concentration vs. time curve (AUC), clearance and antibodies to infliximab (ATI) levels. However, the need to undergo therapeutic escalation later in disease development was significantly associated with higher ATI levels (2.62μg/mL vs. 1.15μg/mL, p=0.028). Moreover, and after adjusting for disease severity, the HR (hazard ratio) for therapeutic escalation was significantly decreased for patients with an ATI concentration below 3μg/mL (HR=0.119, p=0.010), and increased for patients with fecal calprotectin (FC) level above 250μg/g (HR=9.309, p=0.018). In clinically-stable UC patients, IFX pharmacokinetic features cannot predict therapeutic response on a short-term basis. However, high levels of ATIs or FC may be indicative of a future therapeutic escalation.
| S-EPMC5514398 | 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:Background and aimsRecent adult evidence suggests that infliximab (IFX) trough levels (TL) in patients with severe ulcerative colitis (UC) may be decreased. The aims of our study were to compare post-induction IFX TL of children with severe versus moderate UC and to evaluate short- and long-term outcomes.MethodsIn this single-center retrospective study, children with a diagnosis of UC starting IFX with a Pediatric Ulcerative Colitis Activity Index (PUCAI) ≥35 and with available post-induction TL were recruited. UC characteristics, IFX dosage and interval, primary non-response, IFX failure, and surgery after 24 months were collected. Post induction TL, anti-IFX antibodies, and laboratory evaluations at the time of starting IFX were also acquired.ResultsA total of 90 children were enrolled, of whom 39 (43.3%) were classified as severe UC and 51 (56.6%) as moderate UC. Median post-induction IFX TL were lower in severe UC versus moderate group (5.5 vs 10.3; p = 0.03), despite a more frequently intensified IFX regimen. Children in the higher TL quartiles showed increased rates of clinical, biological, and combined remission (p = 0.04, p < 0.001, and p = 0.01, respectively). In a multivariate analysis, a PUCAI ≥65 and time interval from last IFX infusion were the only predictors associated with IFX TL. At 24 months, children in the higher TL quartiles had a decreased risk of IFX failure (p = 0.002). The severe UC group showed a higher risk of IFX failure at 24 months (16/23 (41%) vs. 11/40 (21.6%); p = 0.05). Kaplan-Meier methods demonstrated a trend toward statistical significance, with a two-year cumulative colectomy rate of 15.38% (95% confidence interval (CI) 8.1-15.6%) in children with severe UC and 3.92% (95% CI 2.9-10.8%) in patients with moderate UC (logrank test p = 0.06).ConclusionsChildren starting IFX with severe UC showed lower post-induction TL and poor disease outcomes. Achieving adequate TL was associated with better efficacy outcomes.
| S-EPMC7226697 | biostudies-literature
Project description:Background/aimsThe clinical efficacy and safety of CT-P13 are comparable to originator infliximab for Crohn's disease in CT-P13 3.4 study (NCT02096861). We performed a multivariate logistic analysis to demonstrate the association between early infliximab trough levels and treatment outcomes of CT-P13 and originator infliximab.MethodsEarly serum infliximab trough levels and anti-drug antibody (ADA) levels were compared between CT-P13 (n=100) and originator infliximab (n=98) groups. Receiver operating characteristic (ROC) analysis and multivariate logistic analysis were conducted to identify optimal cutoffs of serum infliximab trough levels and predictive factors for clinical outcomes.ResultsThe median infliximab trough levels were not different between CT-P13 and originator infliximab groups at week 6, week 14, and in median ADA levels at week 14, respectively. ROC analysis found an infliximab concentration threshold of 4.5 μg/mL at week 6 and 4.0 μg/mL at week 14 as the cutoff value with the highest accuracy for the prediction of clinical outcomes. Serum infliximab trough levels at weeks 6 and 14 predicted clinical remission at weeks 30 and 54, and endoscopic remission at week 54. The combinations of clinical remission or C-reactive protein normalization with an early infliximab trough level improved the prediction of long-term clinical or endoscopic remission.ConclusionsA threshold in serum infliximab trough level at week 6 and week 14 was highly predictive for long-term clinical outcomes. There were no statistical differences in serum infliximab trough levels and ADA levels between CT-P13 and originator infliximab.
| S-EPMC10191793 | biostudies-literature
Project description: Not available
| S-EPMC11574158 | biostudies-literature
Project description:Introduction: Up to 40% of patients with Crohn's disease do not respond to treatment with anti-TNF or lose response after the initial benefit. Low drug concentrations have been proposed as the main predictor of treatment failure. Our aim was to study the immunological profile and clinical evolution of patients with Crohn's disease according to the anti-TNF dose and serum trough levels. Methods: Crohn's disease patients in remission treated with infliximab or adalimumab at stable doses for at least for 3 months were included. Serum levels of anti-TNF, TNF-α, interferon-γ, and interleukin IL-12, IL-10, and IL-26 were determined in blood samples taken just before drug administration. Patients were classified according to anti-TNF levels below, within, or above the target level range and the use of intensified doses. Clinical evolution at 6 months was analyzed. Results: A total of 62 patients treated with infliximab (8 on intensified schedule) and 49 treated with adalimumab (7 on intensified schedule) were included. All infliximab-treated patients showed levels within the recommended range, but half of adalimumab-treated patients were below the recommended range. A significant negative relationship between body weight and adalimumab levels was observed, especially in patients treated with intensified doses. Patients with infliximab levels over 8 µg/ml presented higher median IL-10 than patients with in-range levels (84.0 pg/ml, interquartile range [IQR] 77.0-84.8 vs. 26.2 pg/mL, IQR 22.6-38.0; p < 0.001), along with lower values of interferon-γ (312.9 pg/ml, IQR 282.7-350.4 vs. 405.6 pg/ml, IQR 352.2-526.6; p = 0.005). Patients receiving intensified versus non-intensified doses of infliximab showed significantly higher IL-26 levels (91.8 pg/ml, IQR 75.6-109.5 vs. 20.5 pg/ml, IQR 16.2-32.2; p = 0.012), irrespective of serum drug levels. Patients with in-range levels of adalimumab showed higher values of IL-10 than patients with below-range levels (43.3 pg/ml, IQR 35.3-54.0 vs. 26.3 pg/ml, IQR 21.6-33.2; p = 0.001). Patients treated with intensified vs regular doses of adalimumab had increased levels of IL-12 (612.3 pg/ml, IQR 570.2-1353.7 vs. 516.4 pg/mL, IQR 474.5-591.2; p = 0.023). Four patients with low adalimumab levels (19%) and four treated with intensified doses were admitted to a hospital during a follow-up compared to none of the patients with levels within the range. Conclusion: Patients with Crohn's disease treated with infliximab and adalimumab exhibit differences in serum levels of cytokines depending on the drug, dose intensification, and steady state trough serum levels.
| S-EPMC8762261 | biostudies-literature
Project description:BackgroundTherapeutic drug monitoring (TDM) is important in optimizing use of biologics in inflammatory bowel diseases (IBD). However, the role of proactive TDM during remission remains uncertain.MethodsThis retrospective study included patients receiving infliximab (IFX) therapy at Massachusetts General Hospital or Erasmus University Medical Center. All eligible patients had completed induction phase of IFX and were in clinical and endoscopic remission. Our primary outcome was clinical relapse within 2 years after baseline. Multivariable regression models examined the association between infliximab trough levels during remission and relapse, need for IBD-related surgery or hospitalization.ResultsOur study cohort included 110 patients with IBD (72 CD, 38 UC) on IFX maintenance therapy. In total, 12 patients (10.9%) experienced relapse of disease over 2 years. The mean IFX trough level at baseline was 8.0 µg/mL (± 8.6) and did not differ between the institutions. 49.1% of patients had levels < 5 µg/mL and 2.7% had antibodies to infliximab at baseline. There was no difference in the mean IFX trough levels between patients who relapsed (7.5 µg/mL ± 3.7 µg/mL) over 24 months compared to those who did not (8.1 µg/mL ± 7.9 µg/mL, p = 0.815). On multivariable logistic regression analysis, IFX trough levels at baseline were not associated with relapse of disease over 24 months (OR 1.01, 95% CI 0.93-1.09, p = 0.856).ConclusionThis retrospective multicenter study provides evidence that IFX trough levels during quiescent disease do not predict relapse over 2 years, suggestive that proactive TDM in this setting is not warranted.
| S-EPMC8035364 | biostudies-literature
Project description:ObjectivesTo compare infusion reaction rates between rapid infliximab (REMICADE, Janssen Biotech Inc) infusions and previous standard 2- to 3-hour infusions; additionally, to assess patient satisfaction and reduction in chair time associated with rapid infliximab infusions.MethodsPediatric rheumatology and gastroenterology patients receiving maintenance infliximab therapy using a standard 2- to 3-hour titrated infusion had the opportunity to enroll in the non-titrated rapid 1-hour infusion protocol following tolerance of induction dosing at 0, 2, and 6 weeks. Patients were included from December 1, 2017, to March 31, 2018, via retrospective chart review and patient satisfaction surveys.ResultsData were collected on 55 patients receiving a total of 160 rapid infliximab infusions. There were 2 infusion reactions during the enrollment and data collection period, resulting in an overall infusion reaction rate of 1.3%. The patient satisfaction survey results showed all patients were at minimum satisfied with the information provided regarding rapid infliximab, decreased time spent in clinic, ease of scheduling, and overall process.ConclusionsOur data suggest rapid infliximab infusions are safe in pediatric rheumatology and gastroenterology patients receiving maintenance infliximab infusion therapy. The overall infusion reaction rate of 1.3% in this study is well below the accepted infusion reaction rate of standard-length infliximab infusions of 2% to 3%.
| S-EPMC7671021 | biostudies-literature
Project description:BackgroundThe relationship between vitamin D (vit-D) levels and the effectiveness of infliximab (IFX) in patients with Crohn's disease (CD) remains controversial.ObjectiveTo evaluate the interaction between vit-D levels and the response to IFX therapy in patients with CD.MethodsThis was a retrospective cohort study. Serum vit-D and IFX trough concentrations (TC) were measured in 84 patients, and statistical analyses were performed.ResultsThe total vit-D deficiency rate at enrollment, at week 14 and week 38, was 64.3%, 41.67%, and 37.5%, respectively (P < 0.001). CD activity index (CDAI) (120, range, 93-142.75) and simplified endoscopic activity score for CD (SES-CD) (2, range, 0-4) at week 14 were lower than that of enrollment (CDAI, 136.5, range, 101.25-196; SES-CD 13, range, 5-23) (P < 0.001). The biochemical remission (BR), clinical remission (CR), endoscopic remission (ER), and response (ERe) rates of week 38 were 76.1%, 88.5%, 22.4%, and 67.2%, respectively. vit-D levels at enrollment were positively correlated with CDAI at week 38 (P = 0.024). IFX serum TC was related to BR (P = 0.036), CR (P = 0.032) at week 14, and ERe (P = 0.009) at week 38.ConclusionAmong Chinese patients with CD, vit-D levels prior to IFX therapy are related to CDAI scores, and IFX serum TC is associated with BR, CR, and ERe.
| S-EPMC10575748 | biostudies-literature