Role of cyclosporin in preventing or delaying colectomy in children with severe ulcerative colitis

Castro, M.; Papadatou, B.; Ceriati, Emanuela; Knafelz, D.; Angelis, Paola De; Ferretti, Francesca; Gambarara, M.; Diamanti, Antonella; Peppo, Francesco De; Rivosecchi, M.

doi:10.1007/s00423-006-0068-y

Cited by 28 publications

(12 citation statements)

References 16 publications

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“…61 Eight small pediatric cohorts and case series reported the effectiveness of cyclosporine as a salvage therapy in steroid-refractory children with UC with a pooled shortterm success rate (i.e., lack of colectomy) of 81% (95% CI: 76%-86%) but only 39% (29%-49%) in the long term ( Table 2). The long-term success rate was higher in the two studies that introduced immunomodulators at discharge to all patients (pooled rate 71% (55%-83%) 62,63 ). Cyclosporine should only be administered as a bridge to thiopurine treatment; its relatively high toxicity profile (Table 2) dictates that it should be discontinued once thiopurines are effective, typically after 3-4 months.…”

Section: Choice Of Second-line Therapymentioning

confidence: 95%

Acute severe ulcerative colitis in children: A systematic review

Turner

Griffiths

2011

Inflammatory Bowel Diseases

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Pediatric ulcerative colitis (UC) has a more severe phenotype, reflected by more extensive disease and a higher rate of acute severe exacerbations. The pooled steroid-failure rate among 291 children from five studies is 34% (95% confidence interval [CI]: 27%-41%). It is suggested that corticosteroids should be dosed between 1-1.5 mg/kg up to 40-60 mg daily. Food restriction has a limited role in severe UC and should be generally discouraged in children who do not have a surgical abdomen. Appraisal of radiologic findings in children must recognize the variation in colonic width with age and size. Data suggest that the Pediatric UC Activity Index (PUCAI), determined at day 3, should be used to screen for patients likely to fail corticosteroids (>45 points), and at day 5 to dictate the introduction of second-line therapy (>65-70 points). Cyclosporine is successful in children with severe colitis but its use should be restricted to 3-4 months while bridging to thiopurine treatment (pooled short-term success rate 81% [95% CI: 76%-86%]; n = 94 from eight studies). Infliximab may be as effective as cyclosporine (75% pooled short-term response (95% CI: 67%-83%); n = 126, six studies) with a pooled 1-year response of 64% (95% CI: 56%-72%). In toxic megacolon, in patients refractory to one salvage medical therapy, and in chronic severe disease, colectomy may be preferred. Decision-making regarding colectomy in children must consider the toxicity of medication consumed over many future years, the quality of life and self-image associated with either choice, as well as both functional outcomes and, in females, fertility following pouch procedures.

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Section: Choice Of Second-line Therapymentioning

confidence: 95%

Acute severe ulcerative colitis in children: A systematic review

Turner

Griffiths

2011

Inflammatory Bowel Diseases

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“…36 Pediatric cyclosporine data come from 8 retrospective case series (total of 94 children) in which the rate and adverse events were similar to those reported in adults. 7,37 The pooled short-term response was 81%, but only 39% avoided colectomy in the long-term. 7 Heterogeneity in the definition of disease activity, concomitant therapies, follow-up period (1-5 years), dose, and route of administration (half started with oral therapy) limit interpretation of these combined studies.…”

Section: Figurementioning

confidence: 99%

Management of Acute Severe Colitis in Children With Ulcerative Colitis in the Biologics Era

et al. 2016

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BACKGROUND AND OBJECTIVE: Approximately one-third of children with ulcerative colitis will experience at least 1 attack of acute severe colitis (ASC) before 15 years of age. Severe disease can be defined in children when Pediatric Ulcerative Colitis Activity Index is >65 and/or ≥6 bloody stools per day, and/or 1 of the following: tachycardia, fever, anemia, and elevated erythrocyte sedimentation rate with or without systemic toxicity. Our aim was to provide practical suggestions on the management of ASC in children. The goal of medical therapy is to avoid colectomy while preventing complications of disease, side effects of medications, and mortality. METHODS: A systematic search was carried out through Medline via PubMed to identify all articles published in English to date, based on the following keywords “ulcerative colitis,” “pediatric ulcerative colitis,” “biological therapy,” and “acute severe colitis.” Multidisciplinary clinical evaluation is recommended to identify early nonresponders to conventional treatment with intravenous corticosteroids, and to start, if indicated, second-line therapy or “rescue therapy,” such as calcineurin inhibitors (cyclosporine, tacrolimus) and anti–tumor necrosis factor molecules (infliximab). RESULTS: Pediatric Ulcerative Colitis Activity Index is a valid predictive tool that can guide clinicians in evaluating response to therapy. Surgery should be considered in the case of complications or rapid clinical deterioration during medical treatment. CONCLUSIONS: Several pitfalls may be present in the management of ASC, and a correct clinical and therapeutic approach is recommended to reduce surgical risk.

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“…In adults, both IV cyclosporine and oral tacrolimus have also been shown to be effective at inducing remission in IV steroid failure [35–38]. The use of IV cyclosporine has not been as successful in small pediatric cohort studies, which demonstrated short benefit with the use of cyclosporine with successful delay of colectomy of 81% of patients in the acute period, but only 39% avoided colectomy at long-term follow-up; and thus with its significant side effect profile including nephrotoxicity, it is not indicated in maintaining remission [24, 39]. …”

Section: Current Therapiesmentioning

confidence: 99%

Pediatric Ulcerative Colitis: The Therapeutic Road to Infliximab

Puthoor

Zoeten

2013

Biol Ther

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Ulcerative colitis (UC) is a chronic inflammatory bowel disease that has significant morbidities in the pediatric population. Goals of medical therapy include induction and maintenance of remission while preserving the colon and it’s function, while minimizing the risk of treatment related morbidities. For those children who do not respond to initial therapies and progress to develop moderately-to-severely active UC, there has been a dearth of available treatments to help induce remission, necessitating long-term corticosteroid usage, with associated comorbidities of chronic steroid treatment. Significant advances have been made in medical management, including the use of biologic therapies, specifically anti-tumor necrosis factor-α monoclonal antibodies. With the Food and Drug Administration’s recent approval of the use of infliximab, a chimeric anti-tumor necrosis factor-α antibody, for children ≥6 years of age with moderately-to-severely active UC, care providers now have a new treatment regimen to offer this pediatric population.

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Role of cyclosporin in preventing or delaying colectomy in children with severe ulcerative colitis

Cited by 28 publications

References 16 publications

Acute severe ulcerative colitis in children: A systematic review

Acute severe ulcerative colitis in children: A systematic review

Management of Acute Severe Colitis in Children With Ulcerative Colitis in the Biologics Era

Pediatric Ulcerative Colitis: The Therapeutic Road to Infliximab

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