W1193 Safety of Thiopurine Therapy in Inflammatory Bowel Disease (IBD): Long-Term Follow-up Study of 3,900 Patients

Chaparro, María; Ordás, Íngrid; Cabré, E.; García, Valle; Bastida, Guillermo; Peñalva, Mireia; Gomollón, Fernando; García‐Planella, Esther; Merino, Olga; Gutiérrez, Ana; Esteve, María; Andreu, Montserrat; García-Sepulcre, M F; Hinojosa, Joaquín; Vera, Isabel; Muñoz, Fernándo; Mendoza, Juan L.; Cabriada, José Luis; Montoro, Miguel; Barreiro, Manuel; Ceña, Gloria; Saro, Cristina; Manté, Xavier Aldeguer; Barrio, Jesús; Gisbert, Javier P.

doi:10.1016/s0016-5085(10)63087-9

Cited by 61 publications

(123 citation statements)

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“…Immunosuppressant agents such as thiopurines (AZA and 6-MP) induce myelotoxicity in patients with IBD with an incidence rate of 4-7%, most frequently during the first months following initiation of therapy [23,24]. It seems that the incidence of infections in this population, due to AZA/6MP-induced myelotoxicity is quite similar (6.5%) [24].…”

Section: Discussionmentioning

confidence: 99%

Quiescent Crohn’s Disease in Clinical Remission With 6-Mercaptopurine: A Breeding Ground for CMV Pneumonia as Part of a Viral Infection Domino

Panos

2014

J Med Cases

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Cytomegalovirus (CMV) infection is frequently associated with inflammatory bowel disease (IBD). CMV pneumonitis has been reported infrequently in patients with IBD, while there has been one such report in a patient with quiescent Crohn's disease (CD) under long-term immunosuppressant treatment with 6-mercaptopurine (6-MP). We present an unusual case of a 24-year-old male, with fistulized CD in clinical remission under 6-MP, who presented with fever and increased seropurulent fistulae effusion. Shortly after admission, he presented nonproductive cough, pancytopenia, elevated serum aminotransferases, hypoxemia and bilateral pulmonary reticulonodular infiltrates expanding from basal bronchopulmonary segments towards the hila. Positive CMV IgM/IgG, pp65 antigen and CMV-PCR confirmed the diagnosis of CMV pneumonitis. Enterococcus faecium and faecalis were also separately isolated from cultures of two different, concurrent enterocutaneous fistulae. Successful treatment included antiviral and appropriate antibiotic therapy. A subsequent adenovirus co-infection in this patient, demonstrating a viral domino phenomenon, illustrates the difficulty of establishing a final diagnosis in a complex case.

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Section: Discussionmentioning

confidence: 99%

Quiescent Crohn’s Disease in Clinical Remission With 6-Mercaptopurine: A Breeding Ground for CMV Pneumonia as Part of a Viral Infection Domino

Panos

2014

J Med Cases

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“…[142]). About 30 % of patients treated with immunomodulators are reported to discontinue therapy because of intolerable side effects, which may be divided into dose-independent (idiosyncratic) and dose-dependent events [4,143]. Among the most frequent and common idiosyncratic side effects are nausea, vomiting, and diarrhea, which occur in up to 20 % of patients with IBD [104].…”

Section: Side Effectsmentioning

confidence: 99%

“…Among the most frequent and common idiosyncratic side effects are nausea, vomiting, and diarrhea, which occur in up to 20 % of patients with IBD [104]. The more life-threatening common reactions include dose-dependent myelotoxicity (incidence B5 %) and idiosyncratic or dose-dependent hepatotoxicity, which occurs in up to 4 % of thiopurinetreated patients [4] and \1 % of MTX-treated patients [144]. Other reported side effects for thiopurines include an increased risk of pancreatitis, which mainly occurs during the first weeks of administration, infection, lymphoma, and nonmelanoma skin cancer [4,142,145].…”

Section: Side Effectsmentioning

confidence: 99%

“…However, immunomodulators are part of the therapeutic armamentarium for glucocorticoid dependence or resistance, after CD surgery, in the failure of UC maintenance therapy with 5-ASA, and/or as concomitant immunosuppression along with TNF-a inhibitors. Still, conventional weight-based dosing of immunomodulators in IBD leads to intolerance or inefficacy as well as side effects [4]. The increased (clinical) experience with the use of these agents and the unraveling of metabolic profiles obtained during recent years, have improved our understanding of their pharmacokinetics and pharmacodynamics and allowed clinicians to optimize dosing regimens to optimize efficacy and safety.…”

Section: Introductionmentioning

confidence: 99%

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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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“…In a long-term prospectively maintained database of Spanish IBD patients on thiopurines over a median follow-up of 44 months, 17 % of patients discontinued treatment due to adverse events [ 43 ]. The most frequent side effects were nausea (8 %), hepatotoxicity (4 %), myelotoxicity (4 %), and pancreatitis (4 %).…”

Section: Thiopurine Immunosuppressivesmentioning

confidence: 99%

Medical Therapy for Crohn’s Disease: The Present

Fausel

Zisman

2015

Crohn’s Disease

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W1193 Safety of Thiopurine Therapy in Inflammatory Bowel Disease (IBD): Long-Term Follow-up Study of 3,900 Patients

Cited by 61 publications

References 0 publications

Quiescent Crohn’s Disease in Clinical Remission With 6-Mercaptopurine: A Breeding Ground for CMV Pneumonia as Part of a Viral Infection Domino

Quiescent Crohn’s Disease in Clinical Remission With 6-Mercaptopurine: A Breeding Ground for CMV Pneumonia as Part of a Viral Infection Domino

Pharmacology and Optimization of Thiopurines and Methotrexate in Inflammatory Bowel Disease

Medical Therapy for Crohn’s Disease: The Present

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