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Journal of Crohn's & Colitis Jul 2023Scepticism about the efficacy of thiopurines for ulcerative colitis [UC] is rising. This study aimed to evaluate mercaptopurine treatment for UC. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIMS
Scepticism about the efficacy of thiopurines for ulcerative colitis [UC] is rising. This study aimed to evaluate mercaptopurine treatment for UC.
METHODS
In this prospective, randomized, double-blind, placebo-controlled trial, patients with active UC, despite treatment with 5-aminosalicylates [5-ASA], were randomized for therapeutic drug monitoring [TDM]-guided mercaptopurine treatment or placebo for 52 weeks. Corticosteroids were given in the first 8 weeks and 5-ASA was continued. Proactive metabolite-based mercaptopurine and placebo dose adjustments were applied from week 6 onwards by unblinded clinicians. The primary endpoint was corticosteroid-free clinical remission and endoscopic improvement [total Mayo score ≤2 points and no item >1] at week 52 in an intention-to-treat analysis.
RESULTS
Between December 2016 and April 2021, 70 patients were screened and 59 were randomized at six centres. In the mercaptopurine group, 16/29 [55.2%] patients completed the 52-week study, compared to 13/30 [43.3%] on placebo. The primary endpoint was achieved by 14/29 [48.3%] patients on mercaptopurine and 3/30 [10%] receiving placebo (Δ = 38.3%, 95% confidence interval [CI] 17.1-59.4, p = 0.002). Adverse events occurred more frequently with mercaptopurine [808.8 per 100 patient-years] compared to placebo [501.4 per 100 patient-years]. Five serious adverse events occurred, four on mercaptopurine and one on placebo. TDM-based dose adjustments were executed in 22/29 [75.9%] patients, leading to lower mercaptopurine doses at week 52 compared to baseline.
CONCLUSIONS
Optimized mercaptopurine treatment was superior to placebo in achieving clinical, endoscopic and histological outcomes at 1 year following corticosteroid induction treatment in UC patients. More adverse events occurred in the mercaptopurine group.
Topics: Humans; Colitis, Ulcerative; Mercaptopurine; Prospective Studies; Mesalamine; Remission Induction
PubMed: 36847130
DOI: 10.1093/ecco-jcc/jjad022 -
Anais Brasileiros de Dermatologia 2020This is a narrative review of azathioprine. This medication is immunomodulatory and immunosuppressive, and it has been used widely through different medical specialties... (Review)
Review
This is a narrative review of azathioprine. This medication is immunomodulatory and immunosuppressive, and it has been used widely through different medical specialties to modify disease. It has been proven useful for several dermatoses and it has encountered success when used as an off-label indication for other dermatologic diseases. Its mechanism of action is described thoroughly, as well as precautions for monitoring adequate levels in patients using it. Dermatologists should also be aware of the possible adverse events it may present. In dermatology it can be used in bullous and autoimmune diseases, and in other conditions, including intractable pruritus, atopic dermatitis, photodermatoses, psoriasis, and others. Azathioprine offers an alternative as a steroid-sparing agent and this review helps dermatologists prescribe it safely to all patients who require it.
Topics: Azathioprine; Dermatology; Eczema; Humans; Immunosuppressive Agents; Skin Diseases
PubMed: 33250113
DOI: 10.1016/j.abd.2020.05.003 -
[Rinsho Ketsueki] the Japanese Journal... 2022Therapeutic response and drug-induced toxicity have been reported to be associated with genetic variants of drug-metabolizing enzymes and transporters. Recently, new... (Review)
Review
Therapeutic response and drug-induced toxicity have been reported to be associated with genetic variants of drug-metabolizing enzymes and transporters. Recently, new causative variants associated with drug response have been reported by genome-wide association studies (GWASs). Additionally, therapeutic response has been predicted using a model of multiple single-nucleotide polymorphisms. In acute lymphoblastic leukemia (ALL), the genetic variants of NUDT15 associated with therapeutic response to 6-mercaptopurine (6-MP) have been reported by GWASs, and the frequency of NUDT15 variants was higher in Asians. Then, several reports on NUDT15 genetic variants associated with 6-MP-induced toxicities and the tolerable doses and outcomes of 6-MP therapy for ALL have been published in Asian countries. The drugs used in treating hematological malignancies have reported new genetic variants associated with its therapeutic response. However, the association between these genetic variants has not been validated in other populations. Here, we reviewed recent reports on the association between the genetic variants and response to drugs used in treating hematological malignancies, such as 6-MP, cytarabine, methotrexate, and vincristine.
Topics: Humans; Pharmacogenetics; Pyrophosphatases; Genome-Wide Association Study; Antimetabolites, Antineoplastic; Mercaptopurine; Hematologic Neoplasms
PubMed: 36351640
DOI: 10.11406/rinketsu.63.1353 -
The Canadian Journal of Cardiology Aug 2023Recurrent pericarditis is a common and troublesome complication that affects 15%-30% of patients with a previous episode of pericarditis. However, the pathogenesis of... (Review)
Review
Recurrent pericarditis is a common and troublesome complication that affects 15%-30% of patients with a previous episode of pericarditis. However, the pathogenesis of these recurrences is not well understood, and most cases remain idiopathic. Recent advances in medical therapy, including the use of colchicine and anti-interleukin-1 agents like anakinra and rilonacept, have suggested an autoinflammatory rather than an autoimmune mechanism for recurrences with an inflammatory phenotype. As a result, a more personalized approach to treatment is now recommended. Patients with an inflammatory phenotype (fever and elevated C-reactive protein level) should receive colchicine and anti-interleukin-1 agents as first-line therapy, whereas those without systemic inflammation should receive low to moderate doses of corticosteroids (eg, prednisone 0.2-0.5 mg/kg/d as an initial dose) and consider azathioprine and intravenous human immunoglobulins in the case of corticosteroid failure. Tapering of corticosteroids should be slow after achieving clinical remission. In this article, we review the new developments in the management of recurrent pericarditis.
Topics: Humans; Pericarditis; Azathioprine; Adrenal Cortex Hormones; Colchicine; Immunoglobulins, Intravenous; Recurrence
PubMed: 37075863
DOI: 10.1016/j.cjca.2023.04.008 -
Gastroenterology Clinics of North... Dec 2020This article reviews nonbiologic immunosuppressive agents in the induction and maintenance of remission of ulcerative colitis. Based on meta-analyses and North American... (Review)
Review
This article reviews nonbiologic immunosuppressive agents in the induction and maintenance of remission of ulcerative colitis. Based on meta-analyses and North American guidelines, azathioprine, mercaptopurine, and methotrexate monotherapy are not recommended for induction therapy. Thiopurines are recommended in combination with infliximab. Tofacitinib has been shown to be an effective induction agent. Cyclosporine or tacrolimus are calcineurin inhibitors that can be used as induction therapy. Thiopurine monotherapy is suggested or recommended as maintenance therapy for patients who have achieved steroid-induced remission. Methotrexate monotherapy is not recommended. Tofacitinib has been shown to be an effective maintenance agent in moderate to severe disease.
Topics: Azathioprine; Colitis, Ulcerative; Contraindications, Drug; Glucocorticoids; Humans; Immunosuppressive Agents; Maintenance Chemotherapy; Mercaptopurine; Meta-Analysis as Topic; Methotrexate; Piperidines; Pyrimidines; Remission Induction
PubMed: 33121692
DOI: 10.1016/j.gtc.2020.07.003 -
Current Opinion in Pediatrics Dec 2021Pharmacogenomic insights provide an opportunity to optimize medication dosing regimens and patient outcomes. However, the potential for interindividual genomic... (Review)
Review
PURPOSE OF REVIEW
Pharmacogenomic insights provide an opportunity to optimize medication dosing regimens and patient outcomes. However, the potential for interindividual genomic variability to guide medication dosing and toxicity monitoring is not yet standard of care. In this review, we present advances for the thiopurines, anthracyclines and vincristine and provide perspectives on the actionability of pharmacogenomic guidance in the future.
RECENT FINDINGS
The current guideline on thiopurines recommends that those with normal predicted thiopurine methyltransferase and NUDT15 expression receive standard-of-care dosing, while 'poor metabolizer' haplotypes receive a decreased 6-mercaptopurine starting dose to avoid bone marrow toxicity. Emerging evidence established significant polygenic contributions that predispose to anthracycline-induced cardiotoxicity and suggest this knowledge be used to identify those at higher risk of complications. In the case of vincristine, children who express CYP3A5 have a significantly reduced risk of peripheral neuropathy compared with those expressing an inactive form or the CYP3A4 isoform.
SUMMARY
The need for adequately powered pediatric clinical trials, coupled with the study of epigenetic mechanisms and their influence on phenotypic variation and the integration of precision survivorship into precision approaches are featured as important areas for focused investments in the future.
Topics: Cardiotoxicity; Child; Humans; Medical Oncology; Mercaptopurine; Neoplasms; Pharmacogenetics
PubMed: 34561358
DOI: 10.1097/MOP.0000000000001065 -
Practical Neurology Feb 2020Neurologists are very familiar with using corticosteroids and are aware of their considerable risk of adverse effects with prolonged use. Thus, we frequently consider... (Review)
Review
Neurologists are very familiar with using corticosteroids and are aware of their considerable risk of adverse effects with prolonged use. Thus, we frequently consider alternative immunosuppression or corticosteroid sparing agents. However, unlike other specialties, such as rheumatology, there are few indications for corticosteroid-sparing agents in neurology and so our experience is less extensive; even these indications may reduce further as more disease-modifying treatments become available for neurological conditions. Azathioprine is perhaps the most commonly used corticosteroid-sparing agent in neurology. This review aims to remind neurologists of important aspects of azathioprine prescribing, focussing on enhancing patient safety and clinician confidence in its prescribing.
Topics: Azathioprine; Humans; Immunosuppressive Agents; Methyltransferases; Nervous System Diseases; Neurologists
PubMed: 31444234
DOI: 10.1136/practneurol-2018-002161 -
Biochemical and Biophysical Research... Jan 2023Skin is the biggest organ of the human body, which easily gets irritated by exposure to the sun. Skin photoaging and acute photodamage are caused by intense UV-B...
Skin is the biggest organ of the human body, which easily gets irritated by exposure to the sun. Skin photoaging and acute photodamage are caused by intense UV-B radiation. Therefore, it is imperative to find new compounds to prevent skin damage and aging. Mercaptopurine is an immunologic agent commonly used for treating Acute lymphoblastic leukemia and inflammatory bowel disease. The beneficial effects of mercaptopurine on the skin have not been reported, and its intrinsic mechanism of action is unclear. Therefore, this study was to explore mercaptopurine when exposed to UV-B radiation in HacaT cells and C57BL6 mice aging and damage effects. The model of in vivo UV-B-induced skin damage and skin photoaging was established, and the impact of mercaptopurine on cell and animal skin was studied. The study found that mercaptopurine, on the one hand, inhibits cellular and animal senescence. On the other, it inhibits the expression of mitogen-activated protein kinase (MAPK) and the nuclear factor κB (NF-κB), which are important signaling molecules in the early UV-B reaction signaling pathway. In addition, mercaptopurine downregulates matrix metalloproteinase expression, increases collagen fiber content, and facilitates collagen synthesis. Treatment with mercaptopurine also inhibits the expression of inflammatory factors and reduces inflammatory cell infiltration of the skin. In conclusion, our study elucidates mercaptopurine's anti-photoaging and anti-inflammatory activity in cellular and animal models.
Topics: Animals; Humans; Mice; Mercaptopurine; Mice, Inbred C57BL; Skin; Anti-Inflammatory Agents; Skin Aging; Aging; Collagen; Ultraviolet Rays; Fibroblasts
PubMed: 36442232
DOI: 10.1016/j.bbrc.2022.11.035 -
The Korean Journal of Gastroenterology... Feb 2023Autoimmune hepatitis (AIH) is a chronic liver disease, characterized by elevated levels of transaminases, immunoglobulin G, and positive autoantibodies. The disease... (Review)
Review
Autoimmune hepatitis (AIH) is a chronic liver disease, characterized by elevated levels of transaminases, immunoglobulin G, and positive autoantibodies. The disease course is dynamic and presents heterogeneous disease manifestations at diagnosis. This review summarizes the issues regarding the treatment and monitoring of AIH in adult patients. Glucocorticoids and azathioprine are the first line of treatment. Alternative first-line treatments include budesonide or mycophenolate mofetil (MMF). Although no randomized controlled trials have been performed, MMF, cyclosporine, tacrolimus, 6-mercaptopurine, 6-thioguanine, allopurinol, sirolimus, everolimus, infliximab, or rituximab have been attempted in patients not responding to or intolerant to first-line treatments. Most patients require life-long special monitoring, with or without maintenance treatment.
Topics: Adult; Humans; Immunosuppressive Agents; Hepatitis, Autoimmune; Azathioprine; Tacrolimus; Mycophenolic Acid
PubMed: 36824035
DOI: 10.4166/kjg.2023.011 -
Praxis Apr 2022Subacute Flaccid Tetraparesis The patient presented herself with a subacute flaccid tetraparesis. After clinical examination, laboratory analysis, EMG, MRI and muscle...
Subacute Flaccid Tetraparesis The patient presented herself with a subacute flaccid tetraparesis. After clinical examination, laboratory analysis, EMG, MRI and muscle biopsy we diagnosed a statin-associated immune-mediated necrotizing myopathy. Neurorehabilitation and prednisolone therapy as well as immunomodulatory therapy with azathioprine did not result in remission. After two cycles of Privigen®, the patient was almost symptom-free and no longer restricted in everyday life; the CK fell to 400U/l.
Topics: Autoantibodies; Autoimmune Diseases; Azathioprine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases
PubMed: 35473326
DOI: 10.1024/1661-8157/a003828