scholarly journals Reliability evaluation of four different assays for therapeutic drug monitoring of infliximab levels

2018 ◽  
Vol 11 ◽  
pp. 175628481878361 ◽  
Author(s):  
Irene Pérez ◽  
Lidia Fernández ◽  
Silvia Sánchez-Ramón ◽  
Cristina Alba ◽  
Ana Zatarain ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Qualitative Agreement ◽  
Intraclass Correlation ◽  
Cross Sectional Study ◽  
Therapeutic Drug ◽  
Target Interval ◽  
Serum Samples ◽  
Cross Sectional ◽  
Trough Levels

Background: The aim of this study was to evaluate reliability of four different assays for measuring infliximab trough levels and antibodies to infliximab (ATI). Methods: In this non-interventional, cross-sectional study including IBD patients, infliximab levels and ATI were measured using four different assays: Lisa-Tracker, Promonitor, Q-Inflixi and Sanquin. Reliability and agreement for infliximab levels was assessed using the intraclass correlation coefficient (ICC) and Bland–Altman plots. Qualitative agreement for infliximab (based on a pre-established target window of trough levels between 3 µg/ml and 7 µg/ml) and for ATI were estimated by Cohen’s kappa. Results: Serum samples of 84 IBD patients were evaluated for infliximab using the four assays. Reliability was ‘substantial’ between Lisa-Tracker versus Promonitor and ‘almost perfect’ between the remaining assay pairs, with ICCs [95% confidence interval (CI)] ranging from 0.93 (0.70–0.97) for Lisa-Tracker versus Promonitor to 0.97 (0.95–0.98) for Q-Inflixi versus Sanquin. Bland–Altman plots showed significant bias between assays except Promonitor versus Q-Inflixi, which had excellent agreement. The greatest differences in mean infliximab were found between Promonitor versus Lisa-Tracker (–0.91 µg/ml) and Lisa-Tracker versus Q-Inflixi (0.69 µg/ml). Qualitative agreement for infliximab was ‘almost perfect’ for Promonitor versus Q-Inflixi (kappa 0.84) and Q-Inflixi versus Sanquin (kappa 0.81), and ‘substantial’ for the remaining pairs. More than 10% of patients who had infliximab levels within the target interval by Lisa-Tracker had suboptimal concentrations (<3 µg/ml) with Promonitor and Q-Inflixi. Furthermore, 11% of patients within the target interval by Q-Inflixi had supra-optimal levels (>7 µg/ml) by Lisa-Tracker. In the remaining paired comparisons, fewer than 5% of patients were placed in different subgroups. Qualitative agreement for ATI fluctuated between ‘moderate’ and ‘almost perfect’. Conclusions: All four assays seem suitable for therapeutic drug monitoring of infliximab. Promonitor and Q-Inflixi had the best agreement, making those assays fully interchangeable. Systematic biases between Lisa-Tracker with Promonitor and Q-Inflixi suggest that these assays should not be interchanged during the follow up of an individual patient.

scholarly journals N22 Nurse led therapeutic drug monitoring (TDM) of Infliximab in IBD

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S667-S668
Author(s):  
S Gleeson ◽  
K Sugrue ◽  
M Buckley ◽  
J McCarthy
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Trough Concentration ◽  
Drug Monitoring ◽  
Response Assessment ◽  
Symptom Improvement ◽  
Therapeutic Drug ◽  
Serum Samples ◽  
Drug Concentrations ◽  
Biologic Response ◽  
Trough Levels

Abstract Background Therapeutic drug monitoring (TDM) is the clinical practice of measuring serum drug concentrations to guide clinical decision making. Achieving therapeutic drug concentrations has been associated with clinical, endoscopic and histological outcomes in IBD. The use of TDM offers a more personalised treatment approach and is associated with sustained clinical remission. Proactive TDM was introduced to the Mercy University Hospital in 2014 for all patients on biologics. Methods One hundred patients receiving biologic infusion (Infliximab) were evaluated post induction (week 12) for therapeutic drug trough concentration and for clinical response. Serum samples were taken from all IBD patients at week 12. Biologic response assessment forms were complete for all patients to assess symptom improvement. Results Thirty-five per cent of patients had sub therapeutic trough levels at week 12. They subsequently received 3 increased doses of 10mgs/kg and levels were rechecked. Of these 90% achieved therapeutic levels after the dose escalation. 65% of patients had therapeutic levels at week 12. There was a correlation between therapeutic trough levels and patient reported improvement of clinical symptoms in 85% of respondents. Conclusion TDM in our unit facilitates appropriate dose 100 patients receiving biologic infusion (Infliximab) were evaluated post induction (week 12) for therapeutic drug trough concentration and for clinical response. Serum samples were taken from all IBD patients at week 12. Biologic response assessment forms were complete for all patients to assess symptom improvement.

scholarly journals P312 Erythrocyte methotrexate polyglutamate concentrations in patients with Crohn’s Disease: towards a new therapeutic drug monitoring tool

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S339-S339
Author(s):  
M Van de Meeberg ◽  
M Lin ◽  
M Seinen ◽  
H Fidder ◽  
B Oldenburg ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Therapeutic Drug Monitoring ◽  
Crohn's Disease ◽  
Drug Monitoring ◽  
Cross Sectional Study ◽  
Individual Species ◽  
Therapeutic Drug ◽  
Physician Global Assessment ◽  
Cross Sectional ◽  
Large Variability

Abstract Background Methotrexate (MTX) is an immunomodulatory drug for patients with Crohn’s Disease (CD), used as first-line therapy, as a second-line in case of failure to thiopurine, and concomitantly with anti-TNFα agents to decrease production of anti-drug antibodies. Nevertheless, MTX is underutilised in the treatment of CD, despite its proven efficacy and good safety profile. This is for a large part due to the lack of therapeutic drug monitoring (TDM) of MTX because no stable plasma MTX levels are reached. Intracellular MTX-polyglutamates (MTX-PGs), formed after folylpolyglutamate synthetase attaches glutamate residues to MTX, could be used as a TDM tool as MTX-PG is thought to mediate MTX’s efficacy. We present the results of our cross-sectional study in CD patients, aiming to gain insight into erythrocyte MTX-PG levels. Methods CD adults on MTX treatment who visited the outpatient clinic of Amsterdam UMC between May 2019 and February 2020 were included consecutively. An established LC-ESI-MS/MS method1 was used to measure erythrocyte MTX-PGs. Results Nineteen patients were included. Mean disease duration was 17 years (SD±13.7). Montreal disease location and behaviour were as follows (n=): L1 = 2, L2 = 4, L3 = 13; B1 = 11, B2 = 5, B3 = 3. Only 4 patients had a flare according to Physician Global Assessment. Twelve patients received MTX monotherapy, whereas 7 patients were on concomitant anti-TNFα agents. The mean dose of MTX was 15.5 mg (SD±2.8) and 12 (63%) patients had subcutaneous (sc.) MTX. We successfully measured MTX-PG2-5 in 18 patients, showing substantial variability in measured concentrations of total MTX-PG(tot) and the individual species. The median MTX-PGtot was 117.1 nmol/L [min:46.4-max:358.7] with preferential accumulation of MTX-PG3 (43.1 [15.3-96.1]); the least predominant species being MTX-PG5 (9.4 [1.1-24.1]). Patients on sc. compared to oral MTX had higher MTX-PGtot levels (177.8 [58.8-358.7] vs. 93.2 [46.4-120.8] nmol/L, p=0.067) and significantly higher long-chain MTX-PG4-5 levels (55 [3.7-84.3] vs. 8.9 [2.4-15.0] nmol/L, p=0.010); see figure. Conclusion We showed that erythrocyte MTX-PGs can be measured in CD patients by tandem MS. Large variability in concentrations was demonstrated, similar to our previously published results in rheumatoid and juvenile arthritis2,3 which is a pre-requisite for MTX-PG use as a TDM tool. We showed for the first time that MTX-PG accumulation was higher in sc. MTX vs. oral MTX treatment. This work provides the first step towards establishing TDM for MTX in CD, a goal we aim to realize in our upcoming longitudinal study. References

scholarly journals Evaluation of the knowledge of Health Care Professionals regarding Therapeutic Drug Monitoring in Public Hospitals of Lahore, Pakistan

2020 ◽  
Vol V (I) ◽  
pp. 9-16
Author(s):  
Anam Arshad ◽  
Malik Irfan Zulfiqar ◽  
Zahra Hassan Kiani ◽  
Maria Hassan Kiani ◽  
Muhammad Rauf ul Hassan
Keyword(s):  
Health Care ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Health Care Professionals ◽  
Medical Science ◽  
Cross Sectional Study ◽  
Public Hospitals ◽  
Therapeutic Drug ◽  
Cross Sectional ◽  
Developed Country

A cross sectional study was performed among 250 health care professionals from Children Hospital, Jinnah hospital and Services Institute of Medical science Lahore, through a self-designed questionnaire to assess the knowledge of therapeutic drug monitoring (TDM). A total 300 questionnaires were distributed and 250 were returned, giving a response 83%. Out of 300 health care professionals 50 participants do not even know the term TDM. Only 40% participants strongly agreed that TDM is done for all patients. Only 26.8% participants agreed that TDM is carried out for all drugs. Only 63.2% participants agreed that the TDM is very costly process. Only 38.4% strongly agreed that TDM requires extra time of health care professionals and only 36% participants remain neutral to the perception that TDM is requested by patient rather than health care professionals. Limited resources and lack of technical skills are barriers in performing TDM in under-developed country like Pakistan.

scholarly journals Feasibility of Extrapolating Randomly Taken Plasma Samples to Trough Levels for Therapeutic Drug Monitoring Purposes of Small Molecule Kinase Inhibitors

2021 ◽  
Vol 14 (2) ◽  
pp. 119
Author(s):  
Ruben A. G. van Eerden ◽  
Esther Oomen-de Hoop ◽  
Aad Noordam ◽  
Ron H. J. Mathijssen ◽  
Stijn L. W. Koolen
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Small Molecule ◽  
Trough Concentration ◽  
Drug Monitoring ◽  
Half Life ◽  
Kinase Inhibitors ◽  
Therapeutic Drug ◽  
Blood Samples ◽  
Elimination Half ◽  
Trough Levels

Small molecule kinase inhibitors (SMKIs) are widely used in oncology. Therapeutic drug monitoring (TDM) for SMKIs could reduce underexposure or overexposure. However, logistical issues such as timing of blood withdrawals hamper its implementation into clinical practice. Extrapolating a random concentration to a trough concentration using the elimination half-life could be a simple and easy way to overcome this problem. In our study plasma concentrations observed during 24 h blood sampling were used for extrapolation to trough levels. The objective was to demonstrate that extrapolation of randomly taken blood samples will lead to equivalent estimated trough samples compared to measured Cmin values. In total 2241 blood samples were analyzed. The estimated Ctrough levels of afatinib and sunitinib fulfilled the equivalence criteria if the samples were drawn after Tmax. The calculated Ctrough levels of erlotinib, imatinib and sorafenib met the equivalence criteria if they were taken, respectively, 12 h, 3 h and 10 h after drug intake. For regorafenib extrapolation was not feasible. In conclusion, extrapolation of randomly taken drug concentrations to a trough concentration using the mean elimination half-life is feasible for multiple SMKIs. Therefore, this simple method could positively contribute to the implementation of TDM in oncology.

Patient-led Remote IntraCapillary pharmacoKinetic Sampling (fingerPRICKS) for therapeutic drug monitoring in patients with inflammatory bowel disease

2021 ◽  
Author(s):  
Desmond Chee ◽  
Rachel Nice ◽  
Ben Hamilton ◽  
Edward Jones ◽  
Sarah Hawkins ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Blood Sampling ◽  
Therapeutic Drug ◽  
Linear Regression Models ◽  
Cross Sectional ◽  
Immune Mediated ◽  
Low Volume ◽  
Antibody Levels ◽  
At Home

Abstract Background & Aims Because of COVID-19 public health restrictions, telemedicine has replaced conventional outpatient follow up for most patients with chronic immune-mediated inflammatory disorders treated with biologic drugs. Innovative solutions to facilitate remote therapeutic drug monitoring are therefore required. Low-volume intracapillary blood sampling can be undertaken by patients at home and samples returned by post to central laboratories. We sought to report the effect of the COVID-19 pandemic on requests for therapeutic drug monitoring and the equivalence, acceptability and effectiveness of low volume Patient-led Remote IntraCapillary pharmacoKinetic Sampling (fingerPRICKS) compared to conventional venepuncture. Methods We undertook a cross-sectional blood sampling methods comparison study and compared sample types using linear regression models. Drug and antidrug antibody levels were measured using standard ELISAs. Acceptability was assessed using a purpose-designed questionnaire. Results Therapeutic drug monitoring requests for adalimumab (96.5 [70.5 - 106] per week to 52 [33.5 - 57.0], p &lt; 0.001) but not infliximab (184.5 [161.2 - 214.2] to 161 [135 – 197.5], p = 0.34) reduced during the first UK stay-at-home lockdown compared with the preceding six months. Fingerprick sampling was equivalent to conventional venepuncture for adalimumab, infliximab, vedolizumab, and ustekinumab drug, and anti-adalimumab and -infliximab antibody levels. The median (IQR) volume of serum obtained using intracapillary sampling was 195µL (130-210). More than 87% (90/103) patients agreed that intracapillary testing was easy and 69% (71/103) preferred it to conventional venepuncture. In routine care, 75.3% (58/77) patients returned two blood samples within 14 days to permit remote assessment of biologic therapeutic drug monitoring. Conclusions Therapeutic drug monitoring can be undertaken using patient-led remote intracapillary blood sampling and has the potential to be a key adjunct to telemedicine in patients with immune-mediated inflammatory diseases.

scholarly journals A Novel, Rapid, and Low-Volume Assay for Therapeutic Drug Monitoring of Posaconazole and Other Long-Chain Azole-Class Antifungal Drugs

mSphere ◽  
2018 ◽  
Vol 3 (6) ◽  
Author(s):  
Gregory R. Wiedman ◽  
Yanan Zhao ◽  
David S. Perlin
Keyword(s):  
Liquid Chromatography ◽  
Therapeutic Drug Monitoring ◽  
Human Serum ◽  
Drug Monitoring ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Therapeutic Drug ◽  
Serum Samples ◽  
Human Serum Samples ◽  
Long Chain

ABSTRACT Clinicians need a better way to accurately monitor the concentration of antimicrobials in patient samples. In this report, we describe a novel, low-sample-volume method to monitor the azole-class antifungal drug posaconazole, as well as certain other long-chain azole-class antifungal drugs in human serum samples. Posaconazole represents an important target for therapeutic drug monitoring (TDM) due to its widespread use in treating invasive fungal infections and well-recognized variability of pharmacokinetics. The current “gold standard” requires trough and peak monitoring through high-pressure liquid chromatography (HPLC) or liquid chromatography-tandem mass spectroscopy (LC-MS/MS). Other methods include bioassays that use highly susceptible strains of fungi in culture plates or 96-well formats to monitor concentrations. Currently, no method exists that is both highly accurate in detecting free drug concentrations and is also rapid. Herein, we describe a new method using reduced graphene oxide (rGO) and a fluorescently labeled aptamer, which can accurately assess clinically relevant concentrations of posaconazole and other long-chain azole-class drugs in little more than 1 h in a total volume of 100 µl. IMPORTANCE This work describes an effective assay for TDM of long-chain azole-class antifungal drugs that can be used in diluted human serum samples. This assay will provide a quick, cost-effective method for monitoring concentrations of drugs such as posaconazole that exhibit well-documented pharmacokinetic variability. Our rGO-aptamer assay has the potential to improve health care for those struggling to treat fungal infections in rural or resource-limited setting.

scholarly journals Viral load Guided Immunosuppression after Lung Transplantation (VIGILung) – study protocol for a randomized controlled trial

2020 ◽  
Author(s):  
Jens Gottlieb ◽  
Alexander Reuss ◽  
Konstantin Mayer ◽  
Karin Weide ◽  
Carmen Schade-Brittinger ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Lung Transplantation ◽  
Drug Monitoring ◽  
Lung Transplant ◽  
Controlled Trial ◽  
Therapeutic Drug ◽  
Transplant Recipients ◽  
Randomized Controlled ◽  
Lung Transplant Recipients ◽  
Trough Levels

Abstract Background:Immunosuppression including high dose calcineurin-inhibitors (CNI) is essential after lung transplantation. Dosing is usually guided by therapeutic drug monitoring adjusted to target trough levels of CNIs to keep the balance between over-dose causing severe toxicity and increased risk of infections or under-dose with risk of graft-injury.Adaptation of CNI-based immunosuppression by monitoring of Torque-Teno-Virus (TTV) – a latent nonpathogenic DNA virus, measured in whole blood in addition to conventional therapeutic drug monitoring may reduce toxicity of immunosuppression with similar efficacy.Methods/Design:An open-label, randomized, controlled, parallel-group, multicenter trial in lung transplant recipients will be conducted to investigate the safety and efficacy of immunosuppression guided by TTV monitoring as add-on to conventional therapeutic drug monitoring. Adult lung transplant recipients 21 - 42 days after transplantation are eligible to participate. Patients (N = 144) will be randomized 1:1 to the experimental intervention (Arm 1: Immunosuppression guided by TTV monitoring in addition to conventional therapeutic drug monitoring of tacrolimus trough levels) and control intervention (Arm 2: conventional therapeutic drug monitoring). Outcomes will be assessed 12 months after randomization with the change in glomerular filtration rate as the primary endpoint. Secondary endpoints will be additional measurements on renal function, allograft function, incidence of acute rejections, incidence of chronic lung allograft dysfunction, graft loss and infections.Discussion:The results of this randomized controlled trial may reduce toxicity of immunosuppression after lung transplantation while maintaining efficacy of immunosuppression. Study results are transferable to all other solid organ transplantations.Trial registration: ClinicalTrials.gov, NCT04198506. Registered 12 December 2019, https://www.clinicaltrials.gov/show/NCT04198506

scholarly journals P050 Analysis of posaconazole therapeutic drug monitoring in paediatric haematology and oncology patients

2019 ◽  
Vol 104 (7) ◽  
pp. e2.55-e2 ◽  
Author(s):  
Natalie Donald ◽  
Ruth Edwards ◽  
Alison Thomson
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Fungal Infection ◽  
Broad Spectrum ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Paediatric Cancer ◽  
Oncology Patients ◽  
Paediatric Haematology ◽  
Paediatric Patients ◽  
Trough Levels

Posaconazole is a broad spectrum triazole antifungal with activity against a range of invasive fungal pathogens including Candida and Aspergillus species.1 Due to its range of activity it has been shown, by randomised controlled trials, to be superior to fluconazole and itraconazole for prevention of fungal infection in neutropenic patients,2 as well as being cost saving.1 Fungal prophylaxis with posaconazole has become the drug of choice within a paediatric cancer unit due to its broad spectrum of activity however there are significant differences in bioavailability of the suspension and tablet preparations and there is limited data relating to its use in the paediatric population.ObjectiveTo determine if the paediatric cancer unit is undertaking effective dosing and appropriate therapeutic drug monitoring (TDM) of posaconazole in paediatric haematology and oncology patients.MethodsA retrospective analysis of clinical data from 38 paediatric patients treated with posaconazole was undertaken. Patients received either 18–24-mg/kg/day posaconazole suspension in divided doses (maximum 800-mg/day,3 or 6–8-mg/kg/day posaconazole tablets (maximum 300-mg/day). Compliance with this guidance, initial and subsequent levels, efficacy and tolerability were analysed.SettingThe study was undertaken within the XXXX cancer unit; data for patients treated with posaconazole between January 2016 and August 2017 was reviewed.Key findingsThere was good compliance with the dosing advice for liquid and tablet posaconazole with 82% of patients dosed correctly. Due to this, the initial trough level of ≥0.7 mg/L was achieved in 82% of patients within 14 days of treatment initiation; there were no significant differences between formulations. Trough levels were monitored on a monthly basis for 71% of patients but dose adjustments were necessary in 34% of patients. Posaconazole had a good tolerability profile during the study with most side effects resolving on continuation of treatment however one patient had to discontinue the drug due to widespread rash. No patients developed a fungal infection whilst on posaconazole.ConclusionSafe and effective dosing and monitoring of posaconazole suspension and tablet formulations has been undertaken at the XXXX. Trough levels attained the desired target concentration of ≥0.7 mg/L in the majority of patients but dose adjustments were required with both formulations emphasising the need for regular TDM. Posaconazole was well tolerated and clinically effective in preventing fungal infection indicating its appropriateness in this patient group. From this review, a guideline for initiation and appropriate TDM of posaconazole can be developed.ReferencesDranitsaris G, Khoury H. Posaconazole versus fluconazole or itraconazole for prevention of invasive fungal infections in patients undergoing intensive cytotoxic therapy for acute myeloid leukemia or myelodysplasia: a cost effectiveness analysis. Supportive Care in Cancer. 2011; 19(11): 1807–1813.Cornely O, Maertens J, Winston D, et al. Posaconazole vs. Fluconazole or Itraconazole in Patients with Neutropenia. New England Journal of Medicine. 2007; 356(4): 348–359.Bernardo V, Cross S, Crews K, et al. Posaconazole Therapeutic Drug Monitoring in Paediatric Patients and Young Adults with Cancer. The Annals of Pharmacotherapy. 2013; 47: 976–983.

scholarly journals Vancomycin prophylaxis in paediatric patients following cardiac surgery: a retrospective evaluation of trough levels and associated variables

2020 ◽  
Vol 31 (5) ◽  
pp. 667-673
Author(s):  
Leonardo Vallesi ◽  
Tiziana Fragasso ◽  
Simona Benegni ◽  
Giulia Insom ◽  
Luca Di Chiara ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Clinical Predictors ◽  
Paediatric Patients ◽  
Number Of Patients ◽  
Vancomycin Trough ◽  
Optimal Target ◽  
Independent Association ◽  
Trough Levels

Abstract OBJECTIVES Therapeutic drug monitoring during vancomycin administration is recommended. However, little information is available in case of paediatric vancomycin prophylaxis. The aim of this study was to analyse vancomycin trough levels on postoperative day (POD) 2 and 3 after paediatric cardio-surgery to assess the clinical predictors and outcomes associated with vancomycin concentrations and to evaluate whether adjustments are effective to target optimal levels. METHODS A retrospective study was conducted in paediatric patients receiving vancomycin prophylaxis after elective cardio-surgery. Adjustments were made if levels between 20 and 30 (halving subsequent dose) or ˃30 mg/l (dose withheld) were found. RESULTS Vancomycin doses of the 100 examined children (3.7–6.4 years) were 12.8 (2.5), 9.4 (5.4) and 9.7 (4.5) mg/kg, on POD1, 2 and 3, respectively (P = 0.0001). The 200 vancomycin trough levels decreased from 16.9 (11.4) on POD2 to 14.6 (8.5) on POD3 (P = 0.003). Overall, 66 troughs were sub-target, 68 reached the optimal target and 66 were supra-target. On POD2 and 3, 32 and 27 dose adjustments were required, leading to a reduced number of patients with supra-target troughs. Neonates showed a higher number of supra-target levels with respect to non-neonatal patients on both POD2 (P = 0.003) and 3 (P = 0.0001). At multivariable regression analysis, vancomycin levels showed independent association with weight and creatinine levels on both POD2 and 3. Vancomycin levels correlated with ventilation days (P = 0.31, P = 0.039), but not with methicillin-resistant Staphylococcus aureus positivity (P = 0.69). CONCLUSIONS Vancomycin prophylaxis in paediatric cardio-surgery requires strict therapeutic drug monitoring and several dosage adjustments. Supra-target troughs are frequent and neonatal age, weight and creatinine levels significantly affect vancomycin concentrations.

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