Drug rediscovery in gastroenterology: from off-label to on-label use of thioguanine in inflammatory bowel disease.

Drug rediscovery refers to the principle of using 'old' drugs outside the indications mentioned in the summary of product characteristics. In the past decades, several drugs were rediscovered in a wide variety of medical fields. One of the most recent examples is the unconditional registration of thioguanine (TG), a thiopurine derivative, in patients with inflammatory bowel disease in the Netherlands.

A three-dimensional analysis of the development of cranial nerves in human embryos.

To increase our understanding of the etiology of specific neurological disorders (e.g., Duane syndrome, glossoptosis in Pierre Robin sequence), proper knowledge of anatomy and embryology of cranial nerves is necessary.

Systematic review with meta-analysis: SARS-CoV-2 stool testing and the potential for faecal-oral transmission.

Background: Since the start of the COVID-19 pandemic, there have been many scientific reports regarding gastrointestinal manifestations. Several reports indicate the possibility of viral shedding via faeces and the possibility of faecal-oral transmission.

Aims: To critically assess the clinical relevance of testing stool samples and anal swabs and provide an overview of the potential faecal-oral transmission of SARS-CoV-2.

Systematic review with meta-analysis: risk factors for thiopurine-induced leukopenia in IBD.

Background: Thiopurine-induced leukopenia, a frequently observed and potentially life-threatening adverse event, complicates the clinical management of IBD patients.

Aim: To assess risk factors for thiopurine-induced leukopenia in IBD.

Methods: MEDLINE, EMBASE, BIOSIS and Cochrane library were searched for studies reporting at least one risk factor for thiopurine-induced leukopenia.

Clinical Course of Nodular Regenerative Hyperplasia in Thiopurine Treated Inflammatory Bowel Disease Patients.

Nodular regenerative hyperplasia (NRH) is a poorly understood liver condition, which is increasingly recognized in thiopurine-treated patients with inflammatory bowel disease (IBD). It is difficult to establish an optimal approach to NRH patients, because its manifestations are highly variable (from asymptomatic to symptoms of noncirrhotic portal hypertension [NCPH]) and the prognosis is unknown. The aim of this study was to identify NRH cases in IBD patients treated with azathioprine, mercaptopurine, and/or thioguanine, and to describe its clinical course.

High inter-individual variability of serum xanthine oxidoreductase activity in IBD patients.

Objectives: Thiopurines play an essential role in the management of inflammatory bowel diseases (IBD, i.e. Crohn's disease and ulcerative colitis).

Methotrexate and Thioguanine Rescue Therapy for Conventional Thiopurine Failing Ulcerative Colitis Patients: A Multi-center Database Study on Tolerability and Effectiveness.

Background: Patients with active ulcerative colitis (UC) failing conventional therapies are in need of rescue strategies. Due to the fact that accepted step-up therapy with biologicals is expensive and sometimes unavailable, alternative therapies are warranted. Methotrexate (MTX) and thioguanine (TG) have both been suggested as alternative maintenance strategies in conventional thiopurine failing UC patients.

Thiopurines in Inflammatory Bowel Disease: New Findings and Perspectives.

Thiopurines, available as azathioprine, mercaptopurine, and thioguanine, are immunomodulating agents primarily used to maintain corticosteroid-free remission in patients with inflammatory bowel disease. To provide a state-of-the-art overview of thiopurine treatment in inflammatory bowel disease, this clinical review critically summarises the available literature, as assessed by several experts in the field of thiopurine treatment and research in inflammatory bowel disease.

Transient elastography to assess liver stiffness in patients with inflammatory bowel disease.

Background: Liver injury during inflammatory bowel disease (IBD) is primarily diagnosed by liver biopsy, which has a small but serious risk of severe complications. The aim of this study was to assess liver stiffness, and subsequently the prevalence and associations of liver fibrosis in IBD patients with thiopurine therapy and other clinical factors, by using transient elastography (TE).

Methods: In this prospective, international two-center study, included IBD-patients underwent TE measurements.

Analytical Pitfalls of Therapeutic Drug Monitoring of Thiopurines in Patients With Inflammatory Bowel Disease.

The use of thiopurines in the treatment of inflammatory bowel disease (IBD) can be optimized by the application of therapeutic drug monitoring. In this procedure, 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP) metabolites are monitored and related to therapeutic response and adverse events, respectively. Therapeutic drug monitoring of thiopurines, however, is hampered by several analytical limitations resulting in an impaired translation of metabolite levels to clinical outcome in IBD.

Finding hidden treasures in old drugs: the challenges and importance of licensing generics.

Identifying new indications for existing drugs creates new therapeutic options while bypassing much of the costs and time involved with bringing a new drug to market. The rediscovery of a generic drug, however, is a challenging pursuit because there is no formal regulatory approach and a lack of economic interest by pharmaceutical companies. This played a part in the re-registration of thioguanine as a rescue drug for the treatment of patients with inflammatory bowel disease in The Netherlands.

Nodular regenerative hyperplasia rarely leads to liver transplantation: A 20-year cohort study in all Dutch liver transplant units.

Background: Nodular regenerative hyperplasia is an uncommon liver condition associated with several autoimmune disorders and drugs. The clinical symptoms of nodular regenerative hyperplasia vary from asymptomatic to severe complications of portal hypertension (nodular regenerative hyperplasia-syndrome).

Objective: The purpose of this study was to identify the prognosis and optimal management, as well as the role of liver transplantation, in nodular regenerative hyperplasia.

Optimizing Thiopurine Therapy in Inflammatory Bowel Disease Among 2 Real-life Intercept Cohorts: Effect of Allopurinol Comedication?

Background: Thiopurines (azathioprine and mercaptopurine) are frequently used immunosuppressive drugs to maintain remission in patients with inflammatory bowel disease. Half of the conventional thiopurine-derivative users have to discontinue treatment within 5 years, mainly because of intolerable adverse events. Over recent years, different strategies to optimize thiopurine treatment were suggested, yet, studies describing the clinical effectiveness of these strategies remain scarce.

Pharmacology of Thiopurine Therapy in Inflammatory Bowel Disease and Complete Blood Cell Count Outcomes: A 5-Year Database Study.

Background: Thiopurines are the prerequisite for immunomodulation in inflammatory bowel disease (IBD) therapy. When administered in high (oncological) dose, thiopurine metabolites act as purine antagonists, causing DNA-strand breakage and myelotoxicity. In lower IBD dosages, the mode of action is primarily restricted to anti-inflammatory effects.

How I treat my inflammatory bowel disease-patients with thiopurines?

Thiopurines are essential drugs to maintain remission in patients with inflammatory bowel disease (IBD). Thiopurines used in IBD are azathioprine (2.0-2.

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).

Efficacy of thioguanine treatment in inflammatory bowel disease: A systematic review.

Aim: To critically assess the available literature regarding the efficacy of thioguanine treatment in inflammatory bowel disease (IBD) patients, irrespective of the (hepato-) toxicity profile.

Methods: A systematic literature search of the MEDLINE database using PubMed was performed using the keywords "thioguanine", "6-TG", "thioguanine", "inflammatory bowel disease", "IBD", "Crohn's disease", "Ulcerative colitis" and "effectiveness" in order to identify relevant articles published in English starting from 2000. Reference lists of the included articles were cross-checked for missing articles.

Usefulness of mean corpuscular volume as a surrogate marker for monitoring thiopurine treatment in inflammatory bowel disease.

Background: Thiopurines are commonly used drugs in inflammatory bowel disease. Intracellular levels of thiopurine metabolites [i.e.

Clinical Value of Mercaptopurine After Failing Azathioprine Therapy in Patients With Inflammatory Bowel Disease.

Background: Thiopurines have been widely accepted as immunosuppressive therapy in inflammatory bowel disease. However, many patients have to discontinue thiopurines due to intolerance or ineffectiveness. A therapeutically beneficial effect of switching from azathioprine (AZA) to mercaptopurine (MP) after developing adverse events (AEs) has been reported.