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Use in Children

Reviews in IBD

Efficacy and safety reviews


Greifer MK, Markowitz JF.

Update in the treatment of paediatric ulcerative colitis. Expert Opinion on Pharmacotherapy. Vol. 7(14)(pp 1907-1918), 2006.


Abstract:


UC is an important disease in the paediatric population. UC is one of the chronic IBDs, and is medically incurable. However, the arsenal of medications has grown as knowledge of the pathogenesis of this disease advances. This review looks at the classical treatments for children with UC, including the 5-ASAs, corticosteroids and imunomodulators, as well as biological therapy and other, newer modalities.

Safety reviews


No reviews found.

Reviews of safety – general and in other therapeutic areas


No reviews found.

Efficacy studies

RCTs


No studies found.

Non-randomised studies


Fanjiang G, Russell GH, Katz AJ.

Short- and long-term response to and weaning from infliximab therapy in pediatric ulcerative colitis. Journal of Pediatric Gastroenterology & Nutrition. Vol. 44(3)(pp 312-317), 2007.


Abstract:


The authors reviewed the charts of 27 paediatric patients with UC who were treated with infliximab instead of undergoing a colectomy. Patients with new-onset UC refractory to intravenous steroids for 5 to 10 days and patients with non-steroid-dependent UC with an acute exacerbation were classified as acutely ill (n = 16); patients with chronic steroid-dependent UC were classified as chronically ill (n = 11). The Lichtiger Colitis Activity Index (LCAI) was measured for all patients at baseline and at 1 and 2 months after treatment with infliximab was initiated. Patients were regarded as successfully treated if they remained off steroids and avoided colectomy. RESULTS: The acutely ill group had a mean LCAI score of 11.4 at induction and 0.3 after 2 months. The chronically ill group had a mean LCAI score of 11.2 at induction and 5.5 after 2 months. Treatment with infliximab was successful in 75% of acutely ill patients and in 27% of chronically ill patients. Infliximab was discontinued in 80% of successfully treated patients (83% of acutely ill, 67% of chronically ill). These patients had an average of 10 infusions and a mean follow-up time of 10 months from their last infliximab infusion. CONCLUSIONS: These results suggest that infliximab is more effective in acutely ill UC patients than in patients with chronic steroid-dependent UC. In addition, some patients treated with infliximab can be weaned from infliximab and maintain remission.
Cucchiara S, Latiano A, Palmieri O, et al.

Polymorphisms of tumor necrosis factor-a but not MDR1 influence response to medical therapy in pediatric-onset inflammatory bowel disease. Journal of Pediatric Gastroenterology & Nutrition. Vol. 44(2)(pp 171-179), 2007.


Abstract:


The authors investigated the contribution of variants of TNFα and MDR1 genes in the predisposition and response to medical therapy in a large paediatric cohort of patients with Crohn disease and UC. PATIENTS AND METHODS: In this study, 200 patients with CD, 186 patients with UC, 434 parents (217 trios), and 347 healthy unrelated controls were investigated. Single-nucleotide polymorphisms -G308A and -C857T of the TNFα gene and C3435T of the MDR1 gene were investigated and correlated with clinical subphenotypes and efficacy of medical therapy. RESULTS: The frequency of the -308A allele of the TNFα gene was significantly increased in both patients with CD (15%; OR = 2.79; P < 0.01) and patients with UC (11%; OR = 1.96; P < 0.003) compared with controls (6%). Carriers of this allele were 27% in CD (OR = 2.94; P < 0.01) and 19% in UC (OR = 1.86; P = 0.015) compared with 11% in healthy controls. No significant difference was found for both the -C857T and C3435T single-nucleotide polymorphisms. With the genotype/phenotype analysis, no correlation in patients with UC with the MDR1 gene was found. CD carriers of the -308A allele had a higher frequency of surgical resection (35% vs 20%; OR = 2.1; P = 0.035) and more frequent resistance to steroids (22% vs 8%; OR = 0.29; P = 0.032) compared with noncarriers. These findings were confirmed by stepwise logistic regression. CONCLUSIONS: In this paediatric cohort, the promoter -308A polymorphism of TNFα but not the MDR1 gene is significantly involved in the predisposition to both CD and UC. This polymorphism carries a significant reduction in response to steroid therapy, probably leading to a more frequent need for surgical resection.
Akobeng AK.

Infliximab for induction and maintenance therapy for ulcerative colitis. Journal of Pediatric Gastroenterology & Nutrition. Vol. 42(5)(pp 589-590), 2006.


No abstract available.

Erzin Y, Cosgun S, Dobrucali A, et al.

Complicated granulomatous colitis in a patient with Hermansky-Pudlak syndrome, successfully treated with infliximab. Acta Gastroenterologica Belgica. Vol. 69(2)(pp 213-216), 2006.

Abstract:


The bowel disease of the Hermansky-Pudlak syndrome (HPS) is a unique type of IBD with clinical features suggestive of idiopathic UC and pathologic features suggestive of CD. The authors report a patient with HPS which was complicated by granulomatous colitis with perineal and rectovaginal fistulas refractory to antibiotics and AZA but dramatically responded to repeated infusions of infliximab.
Eidelwein AP, Cuffari C, Abadom V, et al.

Infliximab efficacy in pediatric ulcerative colitis. Inflammatory Bowel Diseases. Vol. 11(3)(pp 213-218), 2005.


Abstract:


All paediatric patients with UC who received infliximab between July 2001 and November 2003 at the Johns Hopkins Children's Center were identified. Short- and long-term outcomes and adverse reactions were evaluated. Results: Twelve paediatric patients with UC received infliximab for treatment of fulminant colitis (3 patients), acute exacerbation of colitis (3), steroid-dependent colitis (5), and steroidrefractory colitis (1). Nine patients had a complete short-term response, and 3 had partial improvement. The mean per patient dose of corticosteroid after the first infliximab infusion decreased from 45 mg/day at the first infusion to 22.2 mg/day at 4 weeks (P = 0.02) and 7.8 mg/day at 8 weeks (P = 0.008). Eight patients were classified as long-term responders with a median follow-up time of 10.4 months. Of the 4 long-term nonresponders, 3 underwent colectomy, and the fourth has ongoing chronic symptoms. Three of 4 long-term nonresponders were steroid-refractory compared with 1 of 8 longterm responders. Patients receiving 6-MP had a better response to infliximab. Conclusion: Infliximab should be considered in the treatment of children with symptoms of acute moderate-to-severe UC.
Mamula P, Markowitz JE, Brown KA, et al.

Infliximab as a novel therapy for pediatric ulcerative colitis. Journal of Pediatric Gastroenterology & Nutrition. Vol. 34(3)(pp 307-311), 2002.


Abstract:


The authors collected data on all consecutive paediatric patients with UC who received infliximab at The Children's Hospital of Philadelphia until July 2001. The primary measured outcome was clinical response at 2 days and 2 weeks after infliximab infusion, as measured by the Lichtiger colitis activity index (LCAI) score and the Physician Global Assessment (PGA). Tolerance of the infusions and adverse events were recorded. Results: Nine patients qualified for clinical response analysis. The median Lichtiger colitis activity index score decreased from 11 before the infusion to 1 at 2 days and 2 weeks after the infusion, respectively (P = 0.01 for 2 days and 2 weeks). Seven of 9 (77%) patients had decreased activity of their disease measured by the Physician Global Assessment. Corticosteroid therapy was discontinued in 6 (66%) patients. An infusion reaction developed (generalised pruritus and facial flushing) in 2 patients and an elevated anti-nuclear antibody (ANA) titer of 1:1280 developed in one patient. Conclusion: Infliximab is associated with short-term clinical improvement in children and adolescents with moderate-to-severe UC.
Serrano M-S, Schmidt-Sommerfeld E, Kilbaugh TJ, et al.

Use of infliximab in pediatric patients with inflammatory bowel disease. Annals of Pharmacotherapy. Vol. 35(7-8)(pp 823-828), 2001.


Abstract:


This was a retrospective review of data regarding 18 paediatric and adolescent patients with active CD (n = 15) and UC (n = 3) poorly controlled with conventional therapy. All patients received1 to 6 intravenous infusions of infliximab 5 mg/kg, while receiving their usual medications. RESULTS: All patients experienced clinical improvement, including decrease in the frequency of stooling and resolution of extraintestinal symptoms such as arthropathy, malaise, and skin manifestations after treatment with infliximab. All but one patient had a documented decrease in the erythrocyte sedimentation rate. Prednisone dosage was tapered in all but 2 patients, and discontinued in 7 patients. Intravenous infusion of infliximab was well tolerated. One patient developed a rash several days after the infusion. A patient who received 6 infliximab infusions developed recurrent Staphylococcus aureus infections, as well as septic arthritis and chronic osteomyelitis during the follow-up period, raising the issue of the long-term safety of infliximab. CONCLUSIONS: Treatment of patients with refractory CD and UC with infliximab was associated with remarkable clinical improvement. Although the drug may have an important role in their management, further assessment of long-term safety and efficacy is needed.

Safety studies

IBD


Kolho K-L, Ruuska T, Savilahti E.

Severe adverse reactions to infliximab therapy are common in young children with inflammatory bowel disease. Acta Paediatrica. Vol. 96(1)(pp 128-130), 2007.


Abstract:


Since 2000 the authors have introduced 141 infliximab infusions to 23 children with severe IBD. A total of 7 severe adverse reactions occurred in 26% (6 of 23) of the children. Four reactions were acute (anaphylaxis n = 2; allergic reaction n = 2) and 3/4 of these children were younger than 10 years of age. Two children developed an abscess and one child had septicaemia and brain lesions related to progressive multifocal leucoencephalopathy. Conclusion: adverse reactions to infliximab infusions are common. Young children seem to be prone to severe allergic reactions although they are on AZA and conventional glucocorticoid therapy.
Candon S, Mosca A, Ruemmele F, et al.

Clinical and biological consequences of immunization to infliximab in pediatric Crohn's disease. Clinical Immunology. Vol. 118(1)(pp 11-19), 2006.

Infliximab therapy induces the appearance of neutralising anti-infliximab antibodies. In the paediatric cohort the authors analysed (n = 28) sensitisation occurred in 35.7% patients and was associated with a loss of response to maintenance infusions. In 2 patients presenting high titers of anti-infliximab antibodies, severe infusion reactions were observed, possibly IgE-mediated, precluding further use of the medication. Serum concentrations of TNFα and infliximab were influenced by the presence of anti-infliximab antibodies. The authors propose that surveillance of circulating infliximab and/or TNFα concentration during maintenance therapy represents an indirect but reliable method to monitor anti-infliximab immunisation.
Jacobstein DA, Markowitz JE, Kirschner BS, et al.

Premedication and infusion reactions with infliximab: Results from a paediatric inflammatory bowel disease consortium. Inflammatory Bowel Diseases. Vol. 11(5)(pp 442-446), 2005.


Abstract:


The authors studied the proportion of paediatric patients receiving infliximab for IBD that developed infusion reactions (IRs) and the potential effects of premedication on IR. Methods: Uniformly collected data from a cohort of paediatric patients with IBD enrolled between January 2000 and May 2003 at 6 paediatric centers were analysed. Data were retrospectively reviewed and analysed. Results: A total of 1652 infusions given to 243 patients in 6 centers was analysed. Overall, 60 IRs were recorded in 40 patients (3.6% of infusions, 16.5% of patients). Thirty-three of 243 patients received premedication before the first IR (group 1). Two hundred ten patients did not receive premedication until the development of IRs, if at all (group 2). IRs were more common among patients in group 1 than in group 2 (12/33 versus 28/210, P < 0.01). Of the 28 patients in group 2 with IRs, 10 began receiving premedication with each subsequent infusion, 12 continued without premedications, and 6 had no further infusions recorded. Two of 10 who began receiving premedication had a subsequent IR versus 6 of 12 who did not receive premedication (P = 0.15). Conclusions: IRs occur in a small proportion of infusions among paediatric patients receiving infliximab for IBD. Premedication does not seem to prevent the development of IRs; however, once an IR has occurred, premedication may be indicated to prevent subsequent IRs.
Crandall WV, Mackner LM.

Infusion reactions to infliximab in children and adolescents: Frequency, outcome and a predictive model. Alimentary Pharmacology & Therapeutics. Vol. 17(1)(pp 75-84), 2003.


Abstract:


This was a retrospective review of all infliximab infusions performed at Columbus Children's Hospital from December 1998 through September 2001. Results: Fifty-7 children received 361 infusions. Three hundred and fifty-five of the 361 infusions (98.3%) were completed. Fifty children had 304 repeat infusions. There were a total of 35 infusion related reactions. Female gender and the use of immunosuppressive medications for less than 4 months were risk factors for a reaction to infusion number 2. A reaction to infusion 2 and immunosuppressive use for less than 4 months were risk factors for infusion number 3. Conclusions: The rate of infusion reactions in children receiving infliximab is similar to that in adults. Female gender, immunosuppressive use for less than 4 months and prior infusion reactions may be risk factors for subsequent infusion reactions in children.

Predictors of response

Ferrante M, Vermeire S, Katsanos KH, et al.

Predictors of early response to infliximab in patients with ulcerative colitis. Inflamm Bowel Dis. Vol 13(2)(pp 123-8), 2007.

Abstract:


The objective was to report the outcome of infliximab in UC patients from a single center and to identify predictors of early clinical response. METHODS: The first 100 UC patients (45 female; median age, 37.9 years) who received infliximab at a single center were included. Eighty-four patients received 5 mg/kg infliximab, and 37 patients received a 3-dose infliximab induction at weeks 0, 2, and 6. The Mayo endoscopic subscore, assessed by sigmoidoscopy before inclusion, was 1, 2, and 3 in 5%, 52%, and 43% of patients, respectively. Sixty percent had pancolitis, 63% were on concomitant immunosuppressive therapy, 9% were active smokers, 64% had C-reactive protein ≥5 mg/dL, and 44% were pANCA+/ASCA-. Five patients received infliximab because of severe acute colitis refractory to intravenous corticosteroids. RESULTS: Early complete and partial clinical responses were observed in 41% and 24% of patients. Patients with early clinical response were significantly younger than nonresponders (median age, 35.7 versus 41.6 years, P = 0.041). Patients who were pANCA+/ASCA- had a significantly lower early clinical response (55% versus 76%; odds ratio [OR] = 0.40 (0.16-0.99), P = 0.049). Concomitant immunosuppressive therapy and the use of an infliximab induction scheme did not influence early clinical response. Only 1 of 5 patients who received infliximab for acute steroid-refractory colitis required colectomy within 2 months. CONCLUSIONS: infliximab is an efficient therapy in UC, as shown by 65% early clinical response. A pANCA+/ASCA- serotype and an older age at first infliximab infusion are associated with a suboptimal early clinical response.

Health economics, resources, risk/benefit

Luces C, Bodger K.

Economic burden of inflammatory bowel disease: A UK perspective. Expert Review of Pharmacoeconomics & Outcomes Research. Vol. 6(4)(pp 471-482), 2006.

Abstract:


IBDs are chronic, relapsing conditions that have no permanent drug cure, may occur for the first time in early life and have the potential to produce long-term morbidity. In the era of emerging biological drug therapies, the costs associated with IBD have attracted increased attention. This review considers the available information on the macroeconomics of UC and CD. In relation to direct medical costs, the consistent findings are: hospital (in-patient) costs are incurred by a minority of sufferers but account for approximately half the total cost; and drug costs contribute less than a quarter of the total healthcare costs. Data for levels of costs associated with lost productivity are more variable, but some studies have estimated that 'indirect' costs falling on society exceed medical expenditures. Lifetime costs for IBD are comparable to a number of major diseases, including heart disease and cancer. Over the next 5-10 years, the contribution of drug costs to the overall profile of cost-of-illness will change significantly as biological therapies play an increasing role. A key economic question is whether the health gains realised from exciting new drugs will also lead to reduced expenditures on hospitalisation and surgery.



Acknowledgments


Synopsis author, data search and collation, abstract/summary editing: Dr Gordon Mallarkey, Project Officer, NSW Therapeutic Advisory Group Inc

Reviewed by: Editorial Committee members, NSW Therapeutic Advisory Group Inc.


The Synopsis is copyright of the NSW Therapeutic Advisory Group Inc and NSW Health Department. Apart from any use as permitted under the Copyright Act 1968, no part of this information may be reproduced by any process without written permission. The summaries/abstracts of reviews, guidelines or articles used in this document have been taken from their original sources and, in most cases, edited for conciseness and clarity. Reproduction is not permitted and readers are advised to consult the orginal publications if further information or use of the material is required.
Whilst the information contained in this document has been presented with all due care, and the information is considered to be true and correct at the date of publication, changes in circumstances after publication may impact on the accuracy of the information.
This document is a selected collation of published material and should not be relied on as professional advice other than in this context. The information provided should not be regarded as a substitute for detailed expert advice in individual cases. NSW Therapeutic Advisory Group Inc will accept no responsibility for any loss, claim or damage suffered or caused by any person acting or refraining from action as a result of any material in this document.



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