Absence of nodular regenerative hyperplasia after low-dose 6-thioguanine maintenance therapy in inflammatory bowel disease patients

Boer, Nanne K. H. de; Zondervan, Pieter E.; Gilissen, Lennard P L; Hartog, G. den; Westerveld, B. D.; Derijks, Luc J. J.; Bloemena, Elisabeth; Engels, L.G.J.B.; Bodegraven, Adriaan A. van; Mulder, Chris J.

doi:10.1016/j.dld.2007.10.013

Cited by 54 publications

(39 citation statements)

References 19 publications

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“…[45]) indicate a dose-dependent effect of TG on NRH prevalence. These studies suggest that patients with IBD treated with low-dose TG (\25 mg/day) have a low prevalence (0-4 %) of NRH [46,47], whereas an increased risk of developing NRH (0-27 %) is reported in patients treated with higher dosages (C40 mg/day) of TG [48][49][50]. In contrast, de Boer et al [51] demonstrated a prevalence of 6 % of NRH in thiopurine-naïve IBD patients.…”

Section: Thiopurine Pharmacodynamics and Metabolismmentioning

confidence: 81%

Pharmacology and Optimization of Thiopurines and Methotrexate in Inflammatory Bowel Disease

et al. 2015

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Improving the efficacy and reducing the toxicity of thiopurines and methotrexate (MTX) have been areas of intense basic and clinical research. An increased knowledge on pharmacodynamics and pharmacokinetics of these immunomodulators has optimized treatment strategies in inflammatory bowel disease (IBD). This review focuses on the metabolism and mode of action of thiopurines and MTX, and provides an updated overview of individualized treatment strategies in which efficacy in IBD can be increased without compromising safety. The patient-based monitoring instruments adapted into clinical practice include pretreatment thiopurine S-methyltransferase testing, thiopurine metabolite monitoring, and blood count measurements that may help guiding the dosage to improve clinical outcome. Other approaches for optimizing thiopurine therapy in IBD include combination therapy with allopurinol, 5-aminosalicylates, and/or biologics. Similar strategies are yet to be proven effective in improving the outcome of MTX therapy. Important challenges for the management of IBD in the future relate to individualized dosing of immunomodulators for maximal efficacy with minimal risk of side effects. As low-cost conventional immunomodulators still remain a mainstay in pharmacotherapy of IBD, more research remains warranted, especially to substantiate these tailored management strategies in controlled clinical trials.

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Section: Thiopurine Pharmacodynamics and Metabolismmentioning

confidence: 81%

Pharmacology and Optimization of Thiopurines and Methotrexate in Inflammatory Bowel Disease

et al. 2015

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“…The use of thioguanine was initially discouraged after reports that associated the use of thioguanine with increased rates of nodular regenerative hyperplasia of the liver [72]. However, the results of this study are debated and the true incidence of nodular regenerative hyperplasia might be significantly lower [73]. Recently, Van Asseldonk et al [74] reported a series of 46 UC patients who had failed conventional thiopurine therapy and were treated with thioguanine for a median duration of 22 months.…”

Section: Thiopurinesmentioning

confidence: 94%

Update on the Management of Ulcerative Colitis

Hoentjen

Sakuraba

Hanauer

2011

Curr Gastroenterol Rep

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The treatment options for inflammatory bowel disease have expanded with the introduction of biological therapies. Recently published controlled clinical trials were searched and those that impact the clinical management of ulcerative colitis (UC) are discussed in this review. In the management of mild to moderate UC, mesalamine still remains the first choice of drug. The newly developed once daily formulations have shown equal efficacy to divided doses and possibly portend better compliance owing to a simplified regimen. In outpatients with moderate to severe UC, recent data indicate that infliximab induced and maintained remission leads to decreased colectomy rates and fewer hospitalizations. An alternative anti-tumor necrosis factor (TNF) agent, adalimumab, was also recently shown to be effective for induction of remission in moderate to severe UC. The use of immunosuppressives, such as azathioprine and mercaptopurine, is associated with decreased colectomy rates and thioguanine was shown to be effective in maintaining clinical remission in those who are intolerant to azathioprine/mercaptopurine. In hospitalized patients with steroid resistant severe UC, infliximab and tacrolimus may be alternatives to cyclosporine in those who are otherwise candidates for colectomy. Adequate long-term maintenance therapy with immunosuppressives or anti-TNF therapy is required after rescue therapy for a sustained benefit. Future research is needed to position the available anti-TNF agents and combined immunosuppressive therapy in the treatment of UC to achieve and maintain steroid free remission.

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“…Other reports have failed to demonstrate the same frequency or nature of hepatic injury during treatment with 6-thioguanine, and differences in dose and treatment duration have been proposed to explain the discrepant findings [186][187][188][189][190]. These experiences have justified the recommendation that 6-thioguanine be used in inflammatory bowel disease only after the failure of other options [191], and they have prompted the call for expert-based treatment guidelines [192].…”

Section: -Thioguaninementioning

confidence: 97%

Nonstandard Drugs and Feasible New Interventions for Autoimmune Hepatitis: Part I

Czaja¹

2012

IADT

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Nonstandard drugs that target critical pathogenic pathways or immune regulatory mechanisms constitute the next generation of treatments for autoimmune hepatitis. Mycophenolate mofetil impairs the proliferation of lymphocytes, decreases autoantibody production, and induces apoptosis of activated immunocytes. Patients treated for azathioprine intolerance improve more frequently than patients treated for refractory liver disease (54% versus 10%), and mycophenolate mofetil is emerging as a rescue therapy for this population. Complete corticosteroid withdrawal is possible in 40% of patients treated with mycophenolate mofetil, and the frequency of side effects ranges from 3-34%. Budesonide in combination with azathioprine has normalized liver tests more frequently (47% versus 18%) and with fewer side effects (28% versus 53%) than standard therapy after 6 months. Budesonide is emerging as a frontline treatment in non-cirrhotic patients with uncomplicated disease or contraindications to conventional corticosteroids. Cyclosporine and tacrolimus are effective salvage agents for steroid-refractory disease, but side effects have been common and occasionally serious. The 6- thioguanine nucleotides and rapamycin are feasible treatments for autoimmune hepatitis, but 6-thioguanine has major obstacles to overcome, especially the risk of liver toxicity or nodular regenerative hyperplasia. The nonstandard drug therapies emerging for autoimmune hepatitis reflect the need to supplement or supplant current treatment regimens. None has been licensed for use in autoimmune hepatitis, and their applications have been based on results from small singlecenter experiences.

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Absence of nodular regenerative hyperplasia after low-dose 6-thioguanine maintenance therapy in inflammatory bowel disease patients

Cited by 54 publications

References 19 publications

Pharmacology and Optimization of Thiopurines and Methotrexate in Inflammatory Bowel Disease

Pharmacology and Optimization of Thiopurines and Methotrexate in Inflammatory Bowel Disease

Update on the Management of Ulcerative Colitis

Nonstandard Drugs and Feasible New Interventions for Autoimmune Hepatitis: Part I

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