The Use of Tissue Concentrations of Biological and Small-Molecule Therapies in Clinical Studies of Inflammatory Bowel Diseases.

The introduction of biological therapies has revolutionized inflammatory bowel disease (IBD) management. A critical consideration in developing these therapies is ensuring adequate drug concentrations at the site of action. While blood-based biomarkers have shown limited utility in optimizing treatment (except for TNF-alpha inhibitors and thiopurines), tissue drug concentrations may offer valuable insights.

Performance of Eight Infliximab Population Pharmacokinetic Models in a Cohort of Dutch Children with Inflammatory Bowel Disease.

Background And Objective: Efficacy of infliximab in children with inflammatory bowel disease can be enhanced when serum concentrations are measured and further dosing is adjusted to achieve and maintain a target concentration. Use of a population pharmacokinetic model may help to predict an individual's infliximab dose requirement. The aim of this study was to evaluate the predictive performance of available infliximab population pharmacokinetic models in an independent cohort of Dutch children with inflammatory bowel disease.

Uphill battle: Innovation of thiopurine therapy in global inflammatory bowel disease care.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that encompasses two major conditions: Crohn's disease (CD) and ulcerative colitis (UC). Historically, IBD has been primarily reported in western countries, but over the past decades, its prevalence is rapidly increasing, especially in lower and middle-income countries (LMICs) such as India and China and also in Sub-Saharan Africa. The prevalence of IBD in LMICs has been the subject of growing concern due to the impact of access to public healthcare and the burden it places on healthcare resources.

Early infliximab trough levels in paediatric IBD patients predict sustained remission.

Background: Exposure-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.

Objectives: We aimed to evaluate whether trough levels at week 6 or week 14 predict sustained remission.

The Effectiveness and Safety of First-Line Thioguanine in Thiopurine-Naïve Inflammatory Bowel Disease Patients.

Background: Currently thioguanine is solely used as treatment for inflammatory bowel disease after azathioprine and/or mercaptopurine failure. This study aimed to determine the safety, effectiveness, and 12-month drug survival of thioguanine in thiopurine-naïve patients with inflammatory bowel disease.

Methods: A retrospective cohort study was performed in thiopurine-naïve patients with inflammatory bowel disease treated with thioguanine as first thiopurine derivate.

Therapeutic Drug Monitoring of Vedolizumab in Inflammatory Bowel Disease Patients during Maintenance Treatment-TUMMY Study.

There are limited data on therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) patients treated with vedolizumab (VDZ). Although an exposure-response relation has been demonstrated in the post-induction phase, this relationship is more uncertain in the maintenance phase of treatment. The aim of our study was to determine whether there is an association between VDZ trough concentration and clinical and biochemical remission in the maintenance phase.

Current evidence and clinical relevance of drug-microbiota interactions in inflammatory bowel disease.

Background: Inflammatory bowel disease (IBD) is a chronic relapsing-remitting disease. An adverse immune reaction toward the intestinal microbiota is involved in the pathophysiology and microbial perturbations are associated with IBD in general and with flares specifically. Although medical drugs are the cornerstone of current treatment, responses vary widely between patients and drugs.

Storage conditions of oxytocin in a tropical climate in a low-income country.

Objective: To establish the storage conditions of oxytocin in a health facility in a low-income country with a tropical climate, as suboptimal storage may lead to ineffectiveness of drugs essential to prevent and treat postpartum hemorrhage.

Methods: At Mulago National Referral Hospital (28 000-33 000 deliveries/year) in Kampala, Uganda, temperature logging Safe-Rx cards were placed in boxes of oxytocin and in every known storage location. The route of the boxes through the hospital was tracked for 54 days, and storage conditions were observed.

Genotype-Guided Thiopurine Dosing Does not Lead to Additional Costs in Patients With Inflammatory Bowel Disease.

Background And Aims: Decreased thiopurine S-methyltransferase [TPMT] enzyme activity increases the risk of haematological adverse drug reactions [ADRs] in patients treated with thiopurines. Clinical studies have shown that in patients with inflammatory bowel disease [IBD], pharmacogenetic TPMT-guided thiopurine treatment reduces this risk of ADRs. The aim of this study was to investigate whether this intervention impacts on healthcare costs and/or quality of life.

When patients' invisible work becomes visible: non-adherence and the routine task of pill-taking.

While the biographical dimensions of chronic illness have been well researched, the concrete dimensions of patients' work have not been as thoroughly investigated as yet. With the growing concern for self-management, such research would be timely. This study aims to better understand patients' invisible work by highlighting the causes of unintentional non-adherence as well as strategies for adherence.

Clinical Pharmacokinetic and Pharmacodynamic Considerations in the Treatment of Inflammatory Bowel Disease.

According to recent clinical consensus, pharmacotherapy of inflammatory bowel disease (IBD) is, or should be, personalized medicine. IBD treatment is complex, with highly different treatment classes and relatively few data on treatment strategy. Although thorough evidence-based international IBD guidelines currently exist, appropriate drug and dose choice remains challenging as many disease (disease type, location of disease, disease activity and course, extraintestinal manifestations, complications) and patient characteristics [(pharmaco-)genetic predisposition, response to previous medications, side-effect profile, necessary onset of response, convenience, concurrent therapy, adherence to (maintenance) therapy] are involved.

Patients' beliefs about medicine are associated with early thiopurine discontinuation in patients with inflammatory bowel diseases.

Background: Patients' beliefs about medicine may either reflect the necessity for treatment or concerns regarding the treatment. We explored the extent to which these beliefs have an effect on thiopurine metabolite levels and premature discontinuation in patients with inflammatory bowel disease (IBD).

Patients And Methods: Patients enrolled in the 'Thiopurine response Optimization by Pharmacogenetic testing in Inflammatory Bowel Disease Clinics' (TOPIC) trial were asked to complete the Beliefs about Medicine Questionnaire (BMQ) 4 weeks after thiopurine initiation.

Intentional Nonadherence as a Means to Exert Control.

Medication adherence is a major issue for patients with a chronic illness, who sometimes rationally choose temporary nonadherence. This study aims at better understanding intentional nonadherence and especially why it seems to fluctuate over time. It is based on 48 semi-structured interviews conducted in a hospital in the Netherlands with patients who had been prescribed a medication for a chronic disease for at least 1 year, and who had either type 2 diabetes, hypertension, Parkinson's disease, inflammatory bowel disease, or chronic myeloid leukemia.

More Dose-dependent Side Effects with Mercaptopurine over Azathioprine in IBD Treatment Due to Relatively Higher Dosing.

Background: There are substantial global differences in the preference for mercaptopurine (MP) or its prodrug azathioprine (AZA) as first-choice thiopurine to treat inflammatory bowel diseases. Studies comparing both agents are scarce. Our aim was to compare AZA and MP in thiopurine-naive patients with inflammatory bowel disease for the frequency of side effects and efficacy.

The Effect of Individualized Versus Standardized Parenteral Nutrition on Body Weight in Very Preterm Infants.

Background: This study was designed to evaluate whether standardizing total parenteral nutrition (TPN) is at least non-inferior to TPN with individualized composition in premature infants with a gestational age (GA) < 32 weeks.

Methods: In this retrospective cohort study, all preterm born in or transferred to Maxima Medical Center (MMC) within 24 hours after birth with a GA < 32 weeks were included. The individualized group (2011) was compared to the partially standardized group (2012) and completely standardized group (2014) consequently.

6-methylmercaptopurine-induced leukocytopenia during thiopurine therapy in inflammatory bowel disease patients.

Background And Aim: Thiopurines have a favorable benefit-risk ratio in the treatment of inflammatory bowel disease. A feared adverse event of thiopurine therapy is myelotoxicity, mostly occurring due to toxic concentrations of the pharmacologically active metabolites 6-thioguaninenucleotides. In oncology, myelosuppression has also been associated with elevated 6-methylmercaptopurine (6-MMP).

Short article: The effect of implementation of a treatment algorithm for infliximab on remission rates and drug costs in inflammatory bowel disease patients.

Introduction: The effective, but expensive, drug infliximab is used in patients with inflammatory bowel disease (IBD). Monitoring infliximab trough levels and anti-infliximab antibody (ATI) formation can lead to a more cost-effective use of infliximab therapy. The aim of our study was to investigate the effect of implementation of a treatment algorithm for infliximab in a single-centre IBD cohort, focussing on remission rates and drug costs.