Efficacy of Salvage Therapy and Its Effect on Operative Outcomes in Patients with Ulcerative Colitis

Saito, Eiko; Nagahori, Masakazu; Fujii, Toshimitsu; Ohtsuka, Kazuo; Watanabe, Mamoru

doi:10.1159/000356221

Cited by 9 publications

(7 citation statements)

References 17 publications

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“…Its incidence is increasing more rapidly in Asia than in Europe [1]. However, complete healing and treatment methodology for ulcerative colitis have not been established thus far [2, 3]. Disease conditions in many patients are worsening in the chronic natural course [4].…”

Section: Introductionmentioning

confidence: 99%

Optimized Management of Ulcerative Proctitis: When and How to Use Mesalazine Suppository

et al. 2018

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Background: Ulcerative proctitis, one of the disease types of ulcerative colitis, is considered one of the initial manifestations of ulcerative colitis. Prevention of aggravation of ulcerative proctitis is important for improving the prognosis of ulcerative colitis. Here we reviewed the epidemiology, diagnosis, and management of ulcerative proctitis. Summary: The number of patients with ulcerative proctitis is increasing. Disease extension occurs in many patients with ulcerative proctitis. Differential diagnosis from other chronic proctitis is important and should be performed based on the clinical history and endoscopical and histological features. Mesalazine suppository has been the first-line therapy for patients with ulcerative proctitis because of its high effectiveness and safety. Topical treatment of ulcerative proctitis, particularly using mesalazine suppository has been underused in clinical practice. Key Messages: Mesalazine suppositories are more effective than dose intensification of oral mesalazine for relapsed patients with maintenance dose of oral mesalazine. However, low adherence to rectal mesalazine has hindered remission in patients with ulcerative proctitis.

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Section: Introductionmentioning

confidence: 99%

Optimized Management of Ulcerative Proctitis: When and How to Use Mesalazine Suppository

et al. 2018

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“…Saito et al reported that the frequency of postoperative complications did not increase in patients who underwent colectomy after receiving multiple immunosuppressive agents compared to that in patients who underwent colectomy after receiving only 1 immunosuppressive agent. 40 The benefits and risks should be carefully considered when switching between a calcineurin inhibitor and anti-TNF-α antibody therapy.…”

Section: Switching Between Tacrolimus and Anti-tnf-alpha Antibody Thementioning

confidence: 99%

Tacrolimus for the Treatment of Ulcerative Colitis

et al. 2015

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Tacrolimus is a calcineurin inhibitor used for the treatment of corticosteroid-refractory ulcerative colitis (UC). Two randomized controlled trials and a number of retrospective studies have assessed the therapeutic effect of tacrolimus in UC patients. These studies showed that tacrolimus has excellent short-term efficacy in corticosteroid-refractory patients, with the rates of clinical response ranging from 61% to 96%. However, the long-term prognosis of patients treated with tacrolimus is disappointing, and almost 50% of patients eventually underwent colectomy in long-term follow-up. Tacrolimus can achieve mucosal healing in 40-50% of patients, and this is associated with a favorable long-term prognosis. Anti-tumor necrosis factor (TNF)-α antibodies are another therapeutic option in corticosteroid-refractory patients. A prospective head-to-head comparative study of tacrolimus and infliximab is currently being performed to determine which treatment is more effective in corticosteroid-refractory patients. Several retrospective studies have demonstrated that switching between tacrolimus and anti-TNF-α antibody therapy was effective in patients who were refractory to one of the treatments. Most adverse events of tacrolimus are mild; however, opportunistic infections, especially pneumocystis pneumonia, are the most important adverse events, and these should be carefully considered during treatment. Several issues on tacrolimus treatment in UC patients remain unsolved (e.g., use of tacrolimus as remission maintenance therapy). Further controlled studies are needed to optimize the use of tacrolimus for the treatment of UC.

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“…It is known to be an effective treatment option for refractory ulcerative colitis (UC). A recent study showed that tacrolimus was effective even in the treatment for the infliximab-resistant UC as a salvage therapy [1]. In the tacrolimus treatment for UC, dose adjustment is necessary because the required doses to keep appropriate drug concentrations are significantly different among individuals.…”

Section: Introductionmentioning

confidence: 99%

Tacrolimus Dose Optimization Strategy for Refractory Ulcerative Colitis Based on the Cytochrome P450 3A5 Polymorphism Prediction Using Trough Concentration after 24 Hours

et al. 2018

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Background: In the tacrolimus treatment for refractory ulcerative colitis (UC), dose adjustment is necessary because the required doses to keep appropriate drug concentrations are significantly different among individuals. Cytochrome P450 (CYP) 3A5 polymorphism affects tacrolimus blood concentrations. However, it is difficult to obtain genetic information in real clinical practice. In the present study, we investigated possible factors that may predict CYP3A5 polymorphism and proposed a dose optimization strategy based on the obtained predicting factors. Summary: We retrospectively analyzed 41 patients who underwent remission induction therapy with tacrolimus for UC in our hospital. First, we performed a correlation analysis of CYP3A5 polymorphism and pharmacokinetics. In the CYP3A5 non-expressers, the dose of tacrolimus (mg/kg) was lower and dose-adjusted trough levels (ng/mL per mg/kg) were higher compared with those in expressers. Next, we investigated factors that could predict CYP3A5 polymorphism. Trough concentration 24 h following tacrolimus administration was extracted as a significant factor. When the trough cutoff value at 24 h was set to 2.6 ng/mL, sensitivity and specificity for estimation of CYP3A5 polymorphism were 63 and 96% respectively. Therefore, when the trough concentration 24 h after administration is ≤2.6 ng/mL, the patient can be estimated as a CYP3A5 expresser and an increase in dose should be proposed. Key Message: The trough concentration 24 h after the first tacrolimus administration appears to be a useful predictor of CYP3A5 polymorphism. Performing dose optimization strategy based on the prediction of CYP3A5 polymorphism can lead to earlier and safer remission induction.

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Efficacy of Salvage Therapy and Its Effect on Operative Outcomes in Patients with Ulcerative Colitis

Cited by 9 publications

References 17 publications

Optimized Management of Ulcerative Proctitis: When and How to Use Mesalazine Suppository

Optimized Management of Ulcerative Proctitis: When and How to Use Mesalazine Suppository

Tacrolimus for the Treatment of Ulcerative Colitis

Tacrolimus Dose Optimization Strategy for Refractory Ulcerative Colitis Based on the Cytochrome P450 3A5 Polymorphism Prediction Using Trough Concentration after 24 Hours

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