The long-term risk of continuous immunosuppression using thioguanides in                 inflammatory bowel disease

OʼConnor, Anthony; Qasim, Asghar; O’Moráin, Colm

doi:10.1177/2040622310368736

Cited by 25 publications

(36 citation statements)

References 78 publications

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“…For example, immunomodulatory agents, such as azathioprine and 6-mercaptopurine, cause bone marrow depletion and damage to both white blood cell and hepatic cell populations. Furthermore, results from recent clinical trials confirm that azathioprine is ineffective in UC (Ardizzone et al 2006 ; Kamath et al 2016 ; O’Connor et al 2010 ) and sulfasalazine causes ruptures in liver tissue and decreases platelets count in blood (de Abajo et al 2004 ; Rubin 1994 ). Furthermore, pulmonary disorders are reported in IBD patients treated with chimeric monoclonal antibodies, such as infliximab (Patel et al 2016 ).…”

Section: Introductionmentioning

confidence: 97%

Caffeic acid phenethyl ester is protective in experimental ulcerative colitis via reduction in levels of pro-inflammatory mediators and enhancement of epithelial barrier function

et al. 2017

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BackgroundInhibition of the nuclear factor kappa beta (NF-κβ) pathway has been proposed as a therapeutic target due to its key role in the expression of pro-inflammatory genes, including pro-inflammatory cytokines, chemokines, and adhesion molecules. Caffeic acid phenethyl ester (CAPE) is a naturally occurring anti-inflammatory agent, found in propolis, and has been reported as a specific inhibitor of NF-κβ. However, the impact of CAPE on levels of myeloperoxidases (MPO) and pro-inflammatory cytokines during inflammation is not clear. The aims of this study were to investigate the protective efficacy of CAPE in the mouse model of colitis and determine its effect on MPO activity, pro-inflammatory cytokines levels, and intestinal permeability.MethodDextran sulphate sodium was administered in drinking water to induce colitis in C57/BL6 mice before treatment with intraperitoneal administration of CAPE (30 mg kg−1 day−1). Disease activity index (DAI) score, colon length and tissue histology levels of MPO, pro-inflammatory cytokines, and intestinal permeability were observed.ResultsCAPE-treated mice had lower DAI and tissue inflammation scores, with improved epithelial barrier protection and significant reduction in the level of MPO and pro-inflammatory cytokines.ConclusionOur results show that CAPE is effective in suppressing inflammation-triggered MPO activity and pro-inflammatory cytokines production while enhancing epithelial barrier function in experimental colitis. Thus, we conclude that CAPE could be a potential therapeutic agent for further clinical investigations for treatment of inflammatory bowel diseases in humans.Electronic supplementary materialThe online version of this article (doi:10.1007/s10787-017-0364-x) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 97%

Caffeic acid phenethyl ester is protective in experimental ulcerative colitis via reduction in levels of pro-inflammatory mediators and enhancement of epithelial barrier function

et al. 2017

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“… 13 Immunomodulators such as thiopurines may offer long-term improvements, but achievement of clinical efficacy may require >3 months of treatment 13 and may increase lymphoma risk. 15 , 16 Anti-α4 integrin-targeting agents natalizumab and vedolizumab are approved for use in the treatment of CD in adults, 17 although evidence of efficacy in fistula healing is currently modest. 18 , 19 ECCO guidelines recommended anti-TNF therapy for induction and maintenance therapy in treatment of fistulae in paediatric patients following appropriate antibiotic and surgical management of lesions.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Adalimumab for Treatment of Perianal Fistula in Children with Moderately to Severely Active Crohn’s Disease: Results from IMAgINE 1 and IMAgINE 2

Ruemmele

Rosh

Faubion

et al. 2018

Journal of Crohn's and Colitis

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Background and AimsAdalimumab has been shown to be more effective than placebo in healing fistulae in adults with moderately to severely active Crohn’s disease. The efficacy and safety of adalimumab in healing fistulae in children/adolescents with Crohn’s disease from the 52-week IMAgINE 1 clinical trial, and its open-label extension IMAgINE 2, are reported.MethodsChildren/adolescents with perianal fistulae at baseline of IMAgINE 1 were assessed for fistula closure and improvement during IMAgINE 1 [Weeks 0–52] and from Week 0 of IMAgINE 2 [Week 52 of IMAgINE 1] through to Week 240 of IMAgINE 2 using non-responder imputation.ResultsA total of 36 children/adolescents had fistulae at baseline of IMAgINE 1 and were included in the analysis. Fistula closure and improvement were observed in 44.4% and 52.8%, respectively, at Week 12. Rates of closure and improvement were maintained throughout the analysis period to Week 292. No new safety signals were identified.ConclusionsIn children/adolescents with moderately to severely active, fistulizing Crohn’s disease, adalimumab induced perianal fistula closure and improvement within 12 weeks of treatment, with rates that were sustained for more than 5 years. The safety profile of adalimumab in patients with fistulae at baseline was similar to that of the overall population in IMAgINE 1/2. ClinicalTrials.gov identifiers: IMAgINE 1 (NCT00409682); IMAgINE 2 (NCT00686374).

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“…Lewis and his team confirmed that the benefits of AZA in IBD patients outweigh the possible risk of lymphoma [20]. Altogether, whether or not AZA poses the risk of neoplasia, remains controversial due to the doses used to treat IBD or other diseases [21].…”

Section: All Adverse Effects Induced By Azathioprinementioning

confidence: 99%

Side Effects of Azathioprine in Patients with Ocular Behçet’s disease

Masoumi

Davatchi

Shahram

et al. 2020

Preprint

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Background: Behçet’s disease is an autoimmune, rare, multi-system vasculitis characterized by recurrent oral and genital ulcers, uveitis, skin lesions, and arthritis. Azathioprine has been well established as an effective therapy among other immunosuppressive drugs; however, concerns remain about the safety of azathioprine. This study is conducted to determine various types and prevalence of adverse effects of azathioprine in patients with ocular Behçet’s. Methods: We carried out a cross-sectional study on 165 patients with confirmed diagnosis of Behçet’s who suffered from ocular involvement. Data concerning the different episodes of the disease, including severity, recurrence, relapse, recovery and flare up of Behçet’s disease, were collected retrospectively, as well as the azathioprine dosage and duration of consumption. Results: Of 165 enrolled patients, 103 patients (62.43%) were male and 62 patients (37.57%) were female. Adverse events of treatment with azathioprine occurred in 11 patients (6.67%). Side effects occurred in 11 patients (6.67%) taking azathioprine. These side effects included elevation of liver enzyme in 4 patients (2.43%), hypersensitivity reaction in 2 patients (1.21%), leukopenia in 2 patients (1.21%), nausea in 1 patient (0.61%), skin tumor in 1 patient (0.61%) and concomitant pancreatitis and hepatitis in 1 patient (0.61%). Six of these cases discontinued and five of them tapered the dose. In addition, we observed severe leukopenia in two patients. Conclusion: Administration of azathioprine, with due attention to the signs, symptoms, and severity of the disease, results in a reduced rate of adverse effects, and resolving of the ocular involvement in Behçet’s disease patients.

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The long-term risk of continuous immunosuppression using thioguanides in inflammatory bowel disease

Cited by 25 publications

References 78 publications

Caffeic acid phenethyl ester is protective in experimental ulcerative colitis via reduction in levels of pro-inflammatory mediators and enhancement of epithelial barrier function

Caffeic acid phenethyl ester is protective in experimental ulcerative colitis via reduction in levels of pro-inflammatory mediators and enhancement of epithelial barrier function

Efficacy of Adalimumab for Treatment of Perianal Fistula in Children with Moderately to Severely Active Crohn’s Disease: Results from IMAgINE 1 and IMAgINE 2

Side Effects of Azathioprine in Patients with Ocular Behçet’s disease

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