Use Of Therapeutic Drug Monitoring Research Articles

Prednisolone pharmacokinetics after oral prednisone administration in paediatric patients with kidney transplant.

Glucocorticoids are 1 of the primary treatments in paediatric kidney transplantation. The aims of this study were: (i) to build a population pharmacokinetics (PPK) model of free prednisolone, which is the active form of prednisone, in paediatric kidney transplant recipients; (ii) to identify covariates accounting for interindividual variability (IIV) of pharmacokinetics (PK) parameters; and (iii) to investigate drug exposure-safety relationships. Ninety-seven samples were obtained from 39 paediatric kidney transplant recipients (aged 3.4-17.2years) in order to investigate prednisone PPK. We selected children receiving oral prednisone as part of their immunosuppressive regimen. A PPK analysis was performed using Monolix. A 1-compartment model best described prednisolone concentrations. Large IIV was observed as prednisolone was undetectable at H12 in some patients but could still be detected at H24 in others. Both bodyweight and ciclosporin cotreatment influenced the PK. The clearance (CLU ) and volume of distribution of free prednisolone allometrically scaled to 70 kg were 27.6L/h and 101 L. Ciclosporin cotreatment decreased CLU by 67%. High blood pressure and new onset diabetes after transplantation were associated with daily free prednisolone exposure. This study is the first analysis of prednisolone PPK in kidney-transplanted children. Some of the IIV in the PK parameters was explained by bodyweight and ciclosporin cotreatment. These data suggest that dose adjustment is required after identifying variability factors to optimize efficacy and limit side effects. The use of therapeutic drug monitoring in kidney-transplanted children may be useful, especially with respect to safety issues.

Current safety concerns about the use of antiseizure medications in pregnancy

Introduction Given the high prevalence of epilepsy in women of childbearing potential (15 million out of 50 million people worldwide), antiseizure medication (ASM) use in pregnancy is common. Identifying the safest and most effective ASM to use during pregnancy is often difficult, but also crucially important. The challenge is to balance two needs: maintaining seizure control while minimizing teratogenicity. Areas covered This review looks at seizure- and treatment-related risks to mother and foetus during pregnancy, existing healthcare information programmes, strengths and pitfalls of the main pregnancy registries, known and supposed pharmacokinetic changes during gestation, the utility of therapeutic drug monitoring, and safety concerns. Articles and related content were screened on available publications after January 2000. Expert opinion The use of newer ASMs during pregnancy is still limited, as shown by the paucity of data collected by different pregnancy registries. Choosing these medications can be challenging, partly due to unknown pharmacokinetic modifications in pregnancy, an aspect that serum drug monitoring might help to clarify. The safest treatment is chosen also taking into account the woman’s needs, concerns and wishes, but adequate pre-pregnancy counselling is necessary to properly inform her about personal and foetal risks related both to seizures and to medications.

Use of therapeutic drug monitoring to characterize cefepime-related neurotoxicity.

Data evaluating cefepime thresholds associated with neurotoxicity remain limited. The objectives of this study were to evaluate the incidence of cefepime-related neurotoxicity (CRN) in patients with plasma cefepime concentrations, assess the relationship between cefepime exposure and CRN, investigate clinical factors associated with CRN, and describe electroencephalogram (EEG) abnormalities in CRN. This was a retrospective study of adult inpatients admitted between 2016 and 2018 who received cefepime therapeutic drug monitoring (TDM). Potential CRN cases were identified utilizing a standard definition. The primary outcomes of the study were to determine the incidence of CRN and evaluate the relationship between cefepime trough concentrations, the average daily AUC, and neurotoxicity. Bayesian posteriors were generated for each patient using a cefepime pharmacokinetic (PK) model, and the mean daily area under the concentration-time curve (AUC) was calculated. Multiple regression was performed to assess the association between CRN, cefepime PK, and clinical predictors of neurotoxicity. Four hundred eighty-one patients with 503 hospital encounters received cefepime TDM and were included in the analysis. The incidence of CRN was 4.4% (22/503). Patients with CRN had a higher incidence of renal dysfunction, hypertension, and diabetes mellitus compared to patients without CRN (non-NT). The mean cefepime trough concentration was significantly greater in the CRN patients than in the non-NT group (61.8 ± 33.7 vs. 30 ± 27.7 mg/L, respectively, p= 0.0002). Cefepime trough concentration and renal dysfunction were independently associated with increased risk of CRN in the adjusted multiple regression model. Moderate generalized slowing of the background rhythm was the most common EEG pattern associated with CRN. Delaying cefepime TDM greater than 72 h after the initiation of cefepime was associated with a 3-fold increased risk of CRN. Cefepime should be used cautiously in hospitalized patients with renal dysfunction due to the risk of neurotoxicity. Dose optimization utilizing TDM early in cefepime treatment may minimize adverse effects and improve patient safety.

Accuracy of a precision dosing software program for predicting antibiotic concentrations in critically ill patients.

Critically ill patients with sepsis are predisposed to physiological changes that can reduce the probability of achieving target antibiotic exposures. Precision dosing software programs may be used to improve probability of obtaining these target exposures. To quantify the accuracy of a precision dosing software program for predicting antibiotic concentrations as well as to assess the impact of using software predictions on actual dosing adjustments. The software program ID-ODS was used to predict concentrations for piperacillin, meropenem and vancomycin using patient covariate data with and without the use of therapeutic drug monitoring (TDM) data. The impact of these predictions on actual dosage adjustments was determined by using software predicted concentrations versus measured concentrations. Software predictions for piperacillin and meropenem exhibited large bias that improved with the addition of TDM data (bias improved from -28.8 to -2.0 mg/L for piperacillin and -3.0 to -0.1 mg/L for meropenem). Dosing changes using predicted concentrations of piperacillin and meropenem with TDM data versus measured concentrations were matched on 89.2% (107/120) and 71% (9/69) occasions, respectively. Although vancomycin predictions demonstrated good accuracy with and without TDM, these findings were limited by our small sample size. These data demonstrate that precision dosing software programs may have scope to reasonably predict antibiotic concentrations in critically ill patients with sepsis. The addition of TDM data improves the predictive performance of the software for all three antibiotics and the ability to anticipate the correct dose change required.

Therapeutic Drug Monitoring in Practice for Inflammatory Bowel Disease.

To outline the development, rationale, and practical use of therapeutic drug monitoring in patients with inflammatory bowel disease. Therapeutic drug monitoring is traditionally discussed in terms of a proactive or reactive approach. However, these terms are not always consistently defined and can be confusing when translating research to clinical practice. Personalized approaches incorporating clinical context and precision medicine are emerging. Personalized therapeutic drug monitoring combines a structured and proactive strategy for monitoring biologic concentrations as well as identification of antidrug antibody development or subtherapeutic dosing in the setting of loss of response. Optimizing biologic therapy can improve outcomes and avoid loss of response. Why, when, and how we measure drug troughs and anti-drug antibodies is a moving target, though what is known is that the appropriate and evidence-based use of this practice prevents adverse events and improves outcomes in patients with inflammatory bowel disease.

Nirmatrelvir/ritonavir Use With Tacrolimus in Lung Transplant Recipients: A Single-center Case Series.

Limited data and guidelines exist for using nirmatrelvir/ritonavir in solid organ transplant recipients stabilized on tacrolimus for the treatment of mild-to-moderate coronavirus disease. Concern exists regarding the impact of utilizing a 5-d course of nirmatrelvir/ritonavir with calcineurin inhibitors because of significant drug-drug interactions between ritonavir, a potent cytochrome P450 3A inhibitor, and other cytochrome P450 3A substrates, such as tacrolimus. We report the successful use of nirmatrelvir/ritonavir in 12 outpatient lung transplant recipients with confirmed severe acute respiratory syndrome coronavirus 2 infection stabilized on tacrolimus immunosuppression. All patients stopped tacrolimus and started nirmatrelvir/ritonavir 10 to 14 h after the last dose of tacrolimus. Tacrolimus was withheld and then reinitiated at a modified dose 48 h following the completion of nirmatrelvir/ritonavir therapy. Tacrolimus trough levels were checked during nirmatrelvir/ritonavir therapy and tacrolimus reinitiation. Ten (10/12) patients were able to resume their original tacrolimus dose within 4 d of completing nirmatrelvir/ritonavir therapy and maintain therapeutic levels of tacrolimus. No patients experienced tacrolimus toxicity or acute rejection during the 30-d postcompletion of nirmatrelvir/ritonavir therapy. In this cohort of lung transplant recipients on tacrolimus, we demonstrated that nirmatrelvir/ritonavir can be safely used with close monitoring of tacrolimus levels and appropriate dose adjustments of tacrolimus. Further confirmatory studies are needed to determine the appropriate use of therapeutic drug monitoring and tacrolimus dose following completion of nirmatrelvir/ritonavir in the solid organ transplant population.

Utility of therapeutic drug monitoring of venetoclax in acute myeloid leukemia.

The favorable outcomes of venetoclax-based regimens in older adults with acute myeloid leukemia (AML) may result in its regimen becoming the standard treatment. However, the dosage of venetoclax is fixed, irrespective of body surface area (BSA) or weight. Therefore, individualized dosing using therapeutic drug monitoring (TDM) may help optimize treatment in a safe and effective manner. Twelve patients with AML who received venetoclax-based treatment were enrolled in this study. Blood samples were collected before venetoclax administration, and the minimum plasma concentration (Cmin) was evaluated. The concentration of venetoclax was evaluated using a simple, sensitive, and cost-effective assay using high-performance liquid chromatography, as described previously. The median age was 74 (70-85) years. Ten patients received venetoclax in combination with azacitidine and one patient received low-dose cytarabine (LDAC). The patients BSA ranged from 1.345 to 1.912 m2 (median 1.543). The dose of venetoclax was 400mg with azacitidine, and 600mg with LDAC. In four patients who were taking CYP3A4 inhibitors, venetoclax was reduced to 50mg according to the prescribing information. The Cmin ranged from 0.39 to 2.49, and the patient taking itraconazole showed highest Cmin regardless of the reduction of venetoclax. Most patients showed higher Cmin compared to the data from previous clinical trials, and BSA and venetoclax concentrations showed a negative correlation. Many Asian AML patients > 75years old are petite and receive CYP3A4 inhibitors. Therefore, the TDM of venetoclax may be useful.

Variability of Isavuconazole Trough Concentrations during Longitudinal Therapeutic Drug Monitoring.

Isavuconazole (ISA), a triazole antifungal agent, is licensed for the treatment of invasive aspergillosis and mucormycosis. Therapeutic drug monitoring (TDM) is a cornerstone of treatment efficacy for triazole antifungals due to their pharmacokinetic variability, except for ISA, for which the utility of TDM is still uncertain. We performed a retrospective study that aimed to assess the inter- and intra-individual variability of ISA trough concentrations (Cmin) and to identify the determinants involved in such variability. ISA Cmin measured in adult patients at the Grenoble Alpes University Hospital between January 2018 and August 2020 were retrospectively analyzed. In total, 304 ISA Cmin for 33 patients were analyzed. The median ISA Cmin was 2.8 [25th–75th percentiles: 2.0–3.7] mg/L. The inter- and intra-individual variability was 41.5% and 30.7%, respectively. Multivariate analysis showed independent covariate effects of dose (β = 0.004 ± 3.56 × 10−4, p < 0.001), Aspartate aminotransférase (ASAT) (β = 0.002 ± 5.41 × 10−4, p = 0.002), and protein levels (β = 0.022 ± 0.004, p < 0.001) on ISA Cmin, whereas C reactive protein levels did not show any association. This study, conducted on a large number of ISA Cmin, shows that ISA exposure exhibits variability, explained in part by the ISA dose, and ASAT and protein levels.

P31 Chicken or egg: Inflammatory bowel disease in ankylosing spondylitis

P31 Chicken or egg: Inflammatory bowel disease in ankylosing spondylitis

Quantification of canakinumab in human plasma by liquid chromatography-high resolution mass spectrometry

Canakinumab is a fully-human monoclonal immunoglobulin gamma 1 kappa. This interleukin-1β blocker is used for the treatment of autoinflammatory diseases. Various studies have demonstrated the value of therapeutic drug monitoring of monoclonal antibodies in the management of inflammatory diseases. The purpose of this study was to develop a method to quantify canakinumab plasmatic concentration using liquid chromatography-high-resolution (Orbitrap®) mass spectrometry. The quantification was based on a bottom-up approach with the analysis of one surrogate peptide after an immunopurification of IgG followed by tryptic proteolysis. Rituximab and cetuximab, both IgG1, were tested as internal standards. Chromatographic separation was performed on a bioZenTM Peptide PS-C18 column. Mass detection was conducted in positive ionization mode with Parallel Reaction Monitoring at a resolution of 70,000. The method was fully validated in terms of linearity, sensitivity, selectivity, accuracy and matrix effect. Standards ranged from 2.5 to 75 µg/mL. Intra- and inter-day coefficients of variation ranged from 3.7 to 14.7 %, and accuracy from 97.4 to 104.1 %. This method allowed the determination of canakinumab plasmatic concentrations from eight treated patients. This method is efficient and suitable for routine use in therapeutic drug monitoring or pharmacokinetic studies.

Assessment of current practice for β-lactam therapeutic drug monitoring in French ICUs in 2021: a nationwide cross-sectional survey.

Current guidelines and literature support the use of therapeutic drug monitoring (TDM) to optimize β-lactam treatment in adult ICU patients. To describe the current practice of β-lactam monitoring in French ICUs. A nationwide cross-sectional survey was conducted from February 2021 to July 2021 utilizing an online questionnaire that was sent as an email link to ICU specialists (one questionnaire per ICU). Overall, 119 of 221 (53.8%) French ICUs participated. Eighty-seven (75%) respondents reported having access to β-lactam TDM, including 52 (59.8%) with on-site access. β-Lactam concentrations were available in 24-48 h and after 48 h for 36 (41.4%) and 26 (29.9%) respondents, respectively. Most respondents (n = 61; 70.1%) reported not knowing whether the β-lactam concentrations in the TDM results were expressed as unbound fractions or total concentrations. The 100% unbound fraction of the β-lactam above the MIC was the most frequent pharmacokinetic and pharmacodynamic target used (n = 62; 73.0%). Despite the publication of international guidelines, β-lactam TDM is not optimally used in French ICUs. The two major barriers are β-lactam TDM interpretation and the required time for results.

Current Use of Asparaginase in Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma.

Pediatric Acute Lymphoblastic Leukemia (ALL) cure rates have improved exponentially over the past five decades with now over 90% of children achieving long-term survival. A direct contributor to this remarkable feat is the development and expanded understanding of combination chemotherapy. Asparaginase is the most recent addition to the ALL chemotherapy backbone and has now become a hallmark of therapy. It is generally accepted that the therapeutic effects of asparaginase is due to depletion of the essential amino acid asparagine, thus occupying a unique space within the therapeutic landscape of ALL. Pharmacokinetic and pharmacodynamic profiling have allowed a detailed and accessible insight into the biochemical effects of asparaginase resulting in regular clinical use of therapeutic drug monitoring (TDM). Asparaginase's derivation from bacteria, and in some cases conjugation with a polyethylene glycol (PEG) moiety, have contributed to a unique toxicity profile with hypersensitivity reactions being the most salient. Hypersensitivity, along with several other toxicities, has limited the use of asparaginase in some populations of ALL patients. Both TDM and toxicities have contributed to the variety of approaches to the incorporation of asparaginase into the treatment of ALL. Regardless of the approach to asparagine depletion, it has continually demonstrated to be among the most important components of ALL therapy. Despite regular use over the past 50 years, and its incorporation into the standard of care treatment for ALL, there remains much yet to be discovered and ample room for improvement within the utilization of asparaginase therapy.

Therapeutic Drug Monitoring of Ceftazidime-Avibactam Concentrations in Carbapenem-Resistant K. pneumoniae-Infected Patients With Different Kidney Statuses.

Aims: Carbapenem-resistant K. pneumoniae (CRKP) is the most common carbapenem-resistant Enterobacteriaceae with high mortality. Ceftazidime-avibactam (CAZ-AVI) has exhibited excellent in vitro activity in vivo against CRKP. However, the efficacy of CAZ-AVI in KPC-producing CRKP-infected patients with different kidney statuses varies, such as renal insufficiency, normal renal function, and augmented renal clearance (ARC). We explored the use of therapeutic drug monitoring (TDM) to evaluate the concentration and efficacy of CAZ-AVI in CRKP-infected patients with different kidney statuses. Methods: Serum concentrations for CAZ and AVI were determined by the high-performance liquid chromatography method. Bacterial identification, routine susceptibility testing, renal function index, and others were performed in standard protocols in the hospital’s clinical laboratories. Results: In the two patients with ARC, in case 1, CAZ-AVI 2.5g q6h was used with good efficacy, and the concentrations were up to the pharmacokinetics/pharmacodynamics targets. In Case 2, 2.5 g q8h was used with invalid effectiveness, and AVI Cmin was only 0.797 mg/l, which is lower than the PK/PD target. Case 3 was renal insufficiency using CAZ-AVI 1.25 q8h, and case 4 was normal renal function using 2.5 g q8h. Their concentrations were both up to the PK/PD targets. Conclusion: TDM results demonstrated that CAZ-AVI steady-state plasma concentration varies among patients with different kidney statuses, providing evidence for the utility of TDM of CAZ-AVI in individualized drug dose adjustment. ARC patients may need more CAZ-AVI daily doses than the standard dose.

An 8-year longitudinal study of long-acting injectable (LAI) antipsychotics. Prescription trends and therapeutic drug monitoring to inform precision dosing

IntroductionDespite the widespread use of long-acting injectable (LAI) antipsychotics in schizophrenia and other disorders, there is a lack of longitudinal studies evaluating prescription trends and the usefulness of therapeutic drug monitoring (TDM) to inform dosing. Indeed, LAI prescription varies greatly among different areas of the world and over the years.ObjectivesAssess trends in LAI prescription in 2013-2020 at the Psychiatry Department of Bozen, Italy, and (2) analyze the correlation between dose of prescribed LAIs and blood levels measured via TDM.MethodsParametric statistics.ResultsLAIs were administered to 471 patients (x̅ age±SD=47.2±16.3 years; 56.3% men). The pie chart shows LAI treatment duration, i.e., from 1 to 7 consecutive years. The most used LAIs were haloperidol in 2013-2104 (26.5-31.8%) and paliperidone in 2015-2020 (22.5-25.7%). Dose adjustments were rather frequent, whereas the switch between LAI, due to moderate-to-side effects or unsatisfactory improvement of clinical status, was infrequent (41 cases/8 years). LAI interruption for the same reasons or non-compliance was even more infrequent (10 cases), but in 8 cases it happened for opposite reasons, i.e., achievement of patients’ stabilization and good compliance. The Table shows doses and plasma levels of LAIs. Correlations between doses and plasma levels were: haloperidol: r=-0.037, p=0.620; paliperidone: r=0.290; p=0.000; risperidone: r=0.219, p=0.006; fluphenazine r=0.358, p=0.000; aripiprazole: r=-0.051, p=0.610; olanzapine: r=-0.090, p=0.634.ConclusionsHaloperidol and paliperidone were the most used LAIs. Drug prescription trends and doses were stable over time. A significant positive correlation between dose and plasma level was found for paliperidone, fluphenazine, and aripiprazole.DisclosureNo significant relationships.

Simultaneous Determination of Ledipasvir/Sofosbuvir by LC/MS/MS in Human Plasma and its Pharmacokinetics Application

Background: The rapid growth of COVID-19 infections may result in second wave of infection and an overwhelmed health care providing systems. Ledipasvir and sofosbuvir can be a good choice for management of COVID-19 patients. Development of simple, sensitive, and rapid assay for simultaneous determination of ledipasvir / sofosbuvir to investigate their pharmacokinetic parameters in human plasma, and aid in therapeutic drug moitoring in COVID-19 patients seems to be essential. Besides, its application in bioequivalence study of ledipasvir 90mg / sofosbuvir 400mg film coated tablets generic and reference products to ensure bioanalytical method reliability. Methods: After extraction of ledipasvir and sofosbuvir from human plasma, it was chromatographed with mobile phase consisting of ammonium formate pH 2.8 : acetonitrile (10 : 90 V/V) at flow rate 0.55ml/min, ESI positive mode, and m/z 889.8130.1, 530.3243.1, 739.4565.3 for ledipasvir, sofosbuvir and daclatasvir (internal Standard) respectively. The bioequivalence study was conducted in a partial replicated crossover design invovlving 36 volunteers. The criteria used to assess bioequivalence of the two products were AUC 0-t, AUC 0-inf, Cmax, and Tmax for sofosbuvir, and AUC 0-72, Cmax, and Tmax for ledipasvir. Results: The described method of analysis showed that the average recovery of Ledipasvir and Sofosbuvir from human plasma was 95.180%, and 94.721%. The limit of quantitation was 0.1ng/ml for both drugs, and the correlation coefficient (r2) was equal to 0.999 for ledpasvir and sofosbuvir. Statistical analysis (ANOVA) of the measured parameters showed that there was no significant difference between the two products. Conclusion: The LC/MS/MS method presented is direct, simple, reproducible, sensitive, and linear for determination of ledipasvir / sofosbuvir in plasma, and is adequate for its clinical pharmacokinetic studies, and use in therapeutic drug monitoring. Besides the generic product was found to be biologically equivalent to the reference product regarding their kinetic behavior.

Therapeutic Drug Monitoring of Antifungal Agents in Critically Ill Patients: Is There a Need for Dose Optimisation?

Invasive fungal infections are an important cause of morbidity and mortality, especially in critically ill patients. Increasing resistance rates and inadequate antifungal exposure have been documented in these patients, due to clinically relevant pharmacokinetic (PK) and pharmacodynamic (PD) alterations, leading to treatment failure. Physiological changes such as third spacing (movement of fluid from the intravascular compartment to the interstitial space), hypoalbuminemia, renal failure and hepatic failure, as well as common interventions in the intensive care unit, such as renal replacement therapy and extracorporeal membrane oxygenation, can lead to these PK and PD alterations. Consequently, a therapeutic target concentration that may be useful for one patient may not be appropriate for another. Regular doses do not take into account the important PK variations in the critically ill, and the need to select an effective dose while minimising toxicity advocates for the use of therapeutic drug monitoring (TDM). This review aims to describe the current evidence regarding optimal PK/PD indices associated with the clinical efficacy of the most commonly used antifungal agents in critically ill patients (azoles, echinocandins, lipid complexes of amphotericin B, and flucytosine), provide a comprehensive understanding of the factors affecting the PK of each agent, document the PK parameters of critically ill patients compared to healthy volunteers, and, finally, make recommendations for therapeutic drug monitoring (TDM) of antifungals in critically ill patients.

Adalimumab in Pediatric Inflammatory Bowel Disease.

The introduction of biological agents with strong anti-inflammatory action, such as antitumor necrosis factor (TNF) agents, has changed inflammatory bowel disease (IBD) treatment strategy and goals, and has contributed significantly to improve the long-term prognosis of patients. Moreover, several biological agents are being used or researched in pediatric populations. However, only two biological agents, infliximab (IFX) and adalimumab (ADL), are currently approved for children and adolescents. In pediatric IBD, there are limitations and burdens associated with facilitating mucosal healing (MH) when utilizing these two biological agents. ADL is effective in both naïve patients and those with previous experience with biologics. Beyond clinical remission, this drug is also effective for MH and histological remission. The use of therapeutic drug monitoring to further enhance the effectiveness of ADL treatment can be expected to reduce treatment failure of ADL and pave the way for appropriate treatment in the treat-to-target era. This review paper focuses on ADL, examine studies conducted in children, and determine the role this agent plays against pediatric inflammatory bowel disease.

Therapeutic Drug Monitoring in Perianal Fistulizing Crohn’s Disease

Perianal fistulas are a common complication of Crohn’s disease (CD) that has, historically, been challenging to manage. Despite the strong available evidence that anti-tumor necrosis factor (anti-TNF) agents are useful in the treatment of perianal fistulizing Crohn’s disease (PFCD), a significant number of these patients do not respond to therapy. The use of therapeutic drug monitoring (TDM) in patients with CD receiving biologic agents has evolved and is currently positioned as an important tool to optimize and guide biologic treatment. Considering the treatment of PFCD can represent a challenge; identifying novel tools to improve the efficacy of current treatments is an important unmet need. Given its emerging role in other phenotypes of Crohn’s disease, the use of TDM could also offer an opportunity to enhance the effectiveness of available therapies and improve outcomes in the subset of patients with PFCD receiving biologics. Overall, there is mounting evidence that higher anti-TNF drug levels are associated with better rates of “fistula healing”. However, studies have been limited by their use of subjective outcomes and observational designs. Ultimately, further interventional, randomized controlled trials looking into the relationship between drug exposure and fistula outcomes are needed.

Is There a Best First Line Biological/Small Molecule in IBD: Are We Ready for Sequencing?

Inflammatory bowel disease (IBD) is a chronic, life-long inflammatory condition of the gastrointestinal tract. Treatment strategy depends on the severity of the disease course. IBD physicians need to be aware of the life-long treatment options available. The goal is not only to achieve clinical remission but to halt or stabilize the chronic inflammation in the intestines to prevent further structural damage. Therefore, the use of early biologic therapy is recommended in moderate-to-severe IBD patients. However, in the last decade, use of therapeutic drug monitoring has increased considerably, opening an opportunity for sequencing. This review summarizes the available evidence on biologic and small molecules therapy in Crohn’s disease (CD) and ulcerative colitis (UC) in different clinical scenarios, including perianal CD, the elderly, extra intestinal manifestations, and pregnancy.

Association between olanzapine concentration and metabolic dysfunction in drug-naive and chronic patients: similarities and differences

Second-generation antipsychotics are widely used to treat schizophrenia but their use could induce metabolic dysfunction. To balance efficacy and side effects, various guidelines recommend the use of therapeutic drug monitoring. Given the controversial relationship between olanzapine serum concentration and metabolic dysfunction, its use in clinical practice is still debated. To address this issue, we conducted a prospective cohort study to explore the associations in patients with schizophrenia. Specifically, first-episode drug-naive patients and patients with chronic schizophrenia were recruited. All participants received olanzapine monotherapy for 8 weeks. Anthropometric parameters and metabolic indices were tested at baseline and at week 8, and olanzapine serum concentration was tested at week 4. After 8 weeks of observation, body weight and BMI increased significantly in drug-naive patients. Moreover, triglycerides and LDL increased significantly in both drug-naive and chronic patients. Among chronic patients, those who have never used olanzapine/clozapine before had a significantly higher increase in weight and BMI than those who have previously used olanzapine/clozapine. Furthermore, olanzapine concentration was associated with changes in weight, BMI, and LDL levels in the drug-naive group and glucose, triglyceride and LDL levels in chronic patients who have not used olanzapine/clozapine previously. In conclusion, the metabolic dysfunction induced by olanzapine is more severe and dose-dependent in drug-naive patients but independent in patients with chronic schizophrenia. Future studies with a longer period of observation and a larger sample are warranted.