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

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 < 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.

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P181 Patient-led remote intracapillary pharmacokinetic sampling (fingerPRICKS) for therapeutic drug monitoring in patients with Inflammatory Bowel Disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.308 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S252-S252

Author(s):

D Chee ◽

R Nice ◽

B Hamilton ◽

E Jones ◽

S Hawkins ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Inflammatory Diseases ◽

Blood Sampling ◽

Therapeutic Drug ◽

Biologic Drugs ◽

Immune Mediated ◽

Low Volume ◽

Antibody Levels ◽

At Home

Abstract Background 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. Methods 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 intracapillary fingerprick sampling compared to conventional venepuncture. Drug and antidrug antibody levels were measured using standard ELISAs. Results Therapeutic drug monitoring requests for adalimumab (96.5 [70.5 - 106] per week to 52 [33.5 - 57.0], p < 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 (Figure 1), 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 (Figure 2). In routine care, 75.3% (58/77) patients returned two blood samples within 14 days to permit remote assessment of biologic therapeutic drug monitoring. Conclusion 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.

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Saliva Versus Blood Sampling for Therapeutic Drug Monitoring in Children

Therapeutic Drug Monitoring ◽

10.1097/00007691-199410000-00001 ◽

1994 ◽

Vol 16 (5) ◽

pp. 437-443 ◽

Cited By ~ 43

Author(s):

Rafael Gorodischer ◽

Pascale Burtin ◽

Paul Hwang ◽

Mitchell Levine ◽

Gideon Koren

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Blood Sampling ◽

Therapeutic Drug

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Effect of Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy on Disease Control in Patients With Immune-Mediated Inflammatory Diseases

JAMA ◽

10.1001/jama.2021.21316 ◽

2021 ◽

Vol 326 (23) ◽

pp. 2375

Author(s):

Silje Watterdal Syversen ◽

Kristin Kaasen Jørgensen ◽

Guro Løvik Goll ◽

Marthe Kirkesæther Brun ◽

Øystein Sandanger ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Disease Control ◽

Drug Monitoring ◽

Standard Therapy ◽

Inflammatory Diseases ◽

Infliximab Therapy ◽

Therapeutic Drug ◽

Immune Mediated

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Impact of Pharmacist Scheduling of Blood-Sampling Times for Therapeutic Drug Monitoring

American Journal of Health-System Pharmacy ◽

10.1093/ajhp/45.2.380 ◽

1988 ◽

Vol 45 (2) ◽

pp. 380-382 ◽

Cited By ~ 1

Author(s):

Peter J. Ambrose ◽

Michael Nitake ◽

Carl W. Kildoo

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Blood Sampling ◽

Therapeutic Drug ◽

Sampling Times

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Dried Blood Spot Analysis Suitable for Therapeutic Drug Monitoring of Voriconazole, Fluconazole, and Posaconazole

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00707-13 ◽

2013 ◽

Vol 57 (10) ◽

pp. 4999-5004 ◽

Cited By ~ 36

Author(s):

Kim C. M. van der Elst ◽

Lambert F. R. Span ◽

Kai van Hateren ◽

Karin M. Vermeulen ◽

Tjip S. van der Werf ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Sampling Method ◽

Fungal Infections ◽

Venous Blood ◽

Blood Sampling ◽

Dried Blood Spot ◽

Therapeutic Drug ◽

Venous Blood Sampling ◽

Blood Spot

ABSTRACTInvasive aspergillosis and candidemia are important causes of morbidity and mortality in immunocompromised and critically ill patients. The triazoles voriconazole, fluconazole, and posaconazole are widely used for the treatment and prophylaxis of these fungal infections. Due to the variability of the pharmacokinetics of the triazoles among and within individual patients, therapeutic drug monitoring is important for optimizing the efficacy and safety of antifungal treatment. A dried blood spot (DBS) analysis was developed and was clinically validated for voriconazole, fluconazole, and posaconazole in 28 patients. Furthermore, a questionnaire was administered to evaluate the patients' opinions of the sampling method. The DBS analytical method showed linearity over the concentration range measured for all triazoles. Results for accuracy and precision were within accepted ranges; samples were stable at room temperature for at least 12 days; and different hematocrit values and blood spot volumes had no significant influence. The ratio of the drug concentration in DBS samples to that in plasma was 1.0 for voriconazole and fluconazole and 0.9 for posaconazole. Sixty percent of the patients preferred DBS analysis as a sampling method; 15% preferred venous blood sampling; and 25% had no preferred method. There was significantly less perception of pain with the DBS sampling method (P= 0.021). In conclusion, DBS analysis is a reliable alternative to venous blood sampling and can be used for therapeutic drug monitoring of voriconazole, fluconazole, and posaconazole. Patients were satisfied with DBS sampling and had less pain than with venous sampling. Most patients preferred DBS sampling to venous blood sampling.

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Developing a Nationwide Infrastructure for Therapeutic Drug Monitoring of Targeted Oral Anticancer Drugs: The ON-TARGET Study Protocol

Cancers ◽

10.3390/cancers13246281 ◽

2021 ◽

Vol 13 (24) ◽

pp. 6281

Author(s):

Anna Mc Laughlin ◽

Eduard Schmulenson ◽

Olga Teplytska ◽

Sebastian Zimmermann ◽

Patrick Opitz ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Anticancer Drugs ◽

Drug Monitoring ◽

Drug Exposure ◽

Plasma Concentrations ◽

Blood Sampling ◽

Therapeutic Drug ◽

Study Phase ◽

Blood Samples ◽

Drug Concentrations

Exposure-efficacy and/or exposure-toxicity relationships have been identified for up to 80% of oral anticancer drugs (OADs). Usually, OADs are administered at fixed doses despite their high interindividual pharmacokinetic variability resulting in large differences in drug exposure. Consequently, a substantial proportion of patients receive a suboptimal dose. Therapeutic Drug Monitoring (TDM), i.e., dosing based on measured drug concentrations, may be used to improve treatment outcomes. The prospective, multicenter, non-interventional ON-TARGET study (DRKS00025325) aims to investigate the potential of routine TDM to reduce adverse drug reactions in renal cell carcinoma patients receiving axitinib or cabozantinib. Furthermore, the feasibility of using volumetric absorptive microsampling (VAMS), a minimally invasive and easy to handle blood sampling technique, for sample collection is examined. During routine visits, blood samples are collected and sent to bioanalytical laboratories. Venous and VAMS blood samples are collected in the first study phase to facilitate home-based capillary blood sampling in the second study phase. Within one week, the drug plasma concentrations are measured, interpreted, and reported back to the physician. Patients report their drug intake and toxicity using PRO-CTCAE-based questionnaires in dedicated diaries. Ultimately, the ON-TARGET study aims to develop a nationwide infrastructure for TDM for oral anticancer drugs.

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Adalimumab and infliximab impair SARS-CoV-2 antibody responses: results from a therapeutic drug monitoring study in 11422 biologic-treated patients

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab153 ◽

2021 ◽

Author(s):

Neil Chanchlani ◽

Simeng Lin ◽

Desmond Chee ◽

Benjamin Hamilton ◽

Rachel Nice ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Inflammatory Diseases ◽

Antibody Responses ◽

Therapeutic Drug ◽

Antibody Testing ◽

Drug Levels ◽

Treatment Groups ◽

Immune Mediated ◽

Monitoring Study

Abstract Background and aims Infliximab attenuates serological responses to SARS-CoV-2 infection. Whether this is a class effect, or if anti-TNF level influences serological responses, remains unknown. Methods Seroprevalence and the magnitude of SARS-CoV-2 nucleocapsid antibody responses were measured in surplus serum from 11422 (53.3% (6084) male; median age 36.8 years) patients with immune-mediated inflammatory diseases, stored at six therapeutic drug monitoring laboratories between 29 th January and 30 th September 2020. Data were linked to nationally-held SARS-CoV-2 PCR results to 4 th May 2021. Results Rates of PCR confirmed SARS-CoV-2 infection were similar across treatment groups. Seroprevalence rates were lower in infliximab- and adalimumab- than vedolizumab-treated patients (infliximab: 3.0% (178/5893), adalimumab: 3.0% (152/5074), vedolizumab: 6.7% (25/375), p = 0.003). The magnitude of SARS-CoV-2 reactivity was similar in infliximab- vs adalimumab-treated patients (median 4.30 cut-off index (COI) (1.94 – 9.96) vs 5.02 (2.18 – 18.70), p = 0.164), but higher in vedolizumab-treated patients (median 21.60 COI (4.39 - 68.10, p< 0.004). Compared to patients with detectable infliximab and adalimumab drug levels, patients with undetectable drug levels (<0.8 mg/L) were more likely to be seropositive for SARS-CoV-2 antibodies. One-third of patients who had PCR testing prior to antibody testing failed to seroconvert, all were anti-TNF treated. Subsequent positive PCR-confirmed SARS-CoV-2 was seen in 7.9% (12/152) patients after a median time of 183.5 days (129.8 – 235.3), without differences between drugs. Conclusion Anti-TNF treatment is associated with lower SARS-CoV-2 nucleocapsid seroprevalence and antibody reactivity when compared to vedolizumab-treated patients. Higher seropositivity rates in patients with undetectable anti-TNF levels supports a causal relationship, although confounding factors, such as combination therapy with immunomodulator, may have influenced the results.

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788. Therapeutic Drug Monitoring for Pyrazinamide During Tuberculosis Treatment: What Is the Diagnostic Accuracy?

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.795 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S282-S283

Author(s):

Ginger Anderson ◽

Christopher Vinnard

Keyword(s):

High Risk ◽

Therapeutic Drug Monitoring ◽

Diagnostic Accuracy ◽

Roc Curve ◽

Drug Monitoring ◽

Sparse Sampling ◽

Blood Sampling ◽

Successful Outcome ◽

Therapeutic Drug ◽

Blood Levels

Abstract Background Pyrazinamide (PZA) is a key drug for both drug-sensitive and drug-resistant tuberculosis (TB). Patients co-infected with TB and human immunodeficiency virus (HIV) are more likely to have low blood levels of PZA, associated with inferior outcomes. Therapeutic drug monitoring (TDM) with sparse blood sampling is recommended for high-risk groups, including HIV/TB patients, but the accuracy is uncertain. We performed a pharmacokinetic (PK) simulation study to estimate the diagnostic accuracy of TDM for PZA among HIV/TB patients. Methods We recently performed a population PK study among HIV/TB patients in Botswana, identifying a 1-compartment model with first-order elimination. In the current work, we performed an intensive PK simulation (n = 10,000 patients) to determine the accuracy of sparse blood sampling in identifying HIV/TB patients with low PZA blood levels, as defined by the AUC in a dosing interval (AUC0-24) predictive of successful outcome (363 mg*hr/L). PZA dosing followed WHO guidelines with weight-based dosing bands. In secondary analysis, we examined the peak concentration (Cmax) target predictive of 2-month sputum conversion (58 mg/L). To determine the accuracy of sparse sampling (2- and 6-hours), we performed receiver-operating-characteristic (ROC) analysis, with bootstrapping (n = 1,000) for 95% confidence intervals (CI), and defined accuracy as the area under the ROC curve. Results In this simulation PK study of PZA among HIV/TB patients, the PZA AUC0-24 fell below the target in 29% of patients, while in 71% of patients the PZA Cmax was below the target. For the AUC0-24 target, the area under the ROC curve was 0.69 (95% CI 0.68–0.70) for a single 2-hour sample, increasing to 0.75 (95% CI 0.74–0.76) for 2- and 6-hour samples. For the Cmax target, diagnostic accuracy was similar for a 2-hour sample (0.87, 95% CI 0.86–0.87) and 2- and 6-hour samples (0.88, 95% CI 0.88–0.89). Conclusion We observed modest diagnostic accuracy of TDM for identifying in silico HIV/TB patients with low PZA AUC0-24, and higher accuracy for low Cmax. By identifying diagnostic performance characteristics of sparse sampling strategies, including optimal cut-offs, the ROC framework can support wider implementation of TDM in high-risk TB populations. Disclosures All authors: No reported disclosures.

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