MIMS states that the efficacy and safety of infliximab in paediatric patients have not been established. No notable differences in single dose pharmacokinetics were observed between paediatric and adult CD patients.
The Cochrane review states there is an absence of proper RCTs on the effectiveness of infliximab in the paediatric population. Several non-randomised trials are presented in the Use in Children section of this document. Positive efficacy results were reported, but the trials involved small numbers of patients. Infliximab was more effective in acutely ill UC patients than in patients with chronic steroid-dependent disease (Fanjiang et al, 2007). Eight of 12 paediatric UC patients were classified as long-term responders in another study (Eidelwein et al 2005)
Crandall et al (2003) reported that 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 were thought to be risk factors for subsequent infusion reactions in children. Jacobstein et al (2005) reported 60 infusion reactions from a total of 1652 infusions given to 243 paediatric inflammatory bowel disease (IBD) patients. Kohlo et al (2007) found that adverse reactions to infliximab infusions were common in children with IBD and that young children seemed to be prone to severe allergic reactions despite azathioprine and conventional glucocorticoid therapy. Candon et al (2006) reported that infliximab therapy induced the appearance of neutralising anti-infliximab antibodies in 10 of 28 paediatric CD patients, which resulted in a loss of response to maintenance infusions.
MIMS states that no major differences were observed in the pharmacokinetics of Remicade in elderly (65 to 80 years) RA patients.
Clinical studies of Remicade did not include sufficient numbers of CD patients aged 65 and over to determine whether they respond differently from patients aged 18 to 65.
Studies have not been performed in patients with liver or renal disease. Since elderly patients have a greater frequency of decreased hepatic, renal and/or cardiac function and a greater frequency of concomitant disease and/or other drug therapy, caution in the treatment of elderly patients is recommended. While changes in the ageing immune system may affect the risk of infection, in a cohort study of 15,597 US Medicare beneficiaries (>65 years), Schneeweiss et al (Arthritis and Rheumatism, 2007 – see Safety section) found no increase in the rate of bacterial infections among TNFα inhibitors compared methotrexate.
The UK National Horizon Scanning Centre (2005) say it is difficult to estimate the cost impact of infliximab use in UC but it may lead to a net saving due to possible reduction in hospitalisation and surgical procedures. They state that minimal additional training of healthcare professionals will be required because infliximab is already used in CD treatment. A UK study states that only a minority of CD and UC sufferers are hospital inpatients but they account for approximately half the direct medical costs of IBD treatment. Drug costs contribute less than a quarter of the total healthcare costs (Luces & Bodger 2006). Lifetime costs for IBD are comparable to a number of major diseases, including heart disease and cancer. They state that in the next 5 to10 years, the contribution of drug costs will increase as biological therapies become used more widely. The key economic question is whether the health gains from these drugs will lead to reduced expenditures on hospitalisation and surgery.
This document contains summary data from published reviews, guidelines and articles to help drug and therapeutic committees make decisions about use of infliximab in ulcerative colitis (UC). It is not a Position Statement and does not represent recommendations from the NSW Therapeutic Advisory Group.
The data was collated after searching websites of organisations/publications including: ACP Journal Club, ADRAC, Australian Clinical Trials Registry, Bandolier, Canadian Agency for Drugs and Technologies in Health (CADTH), Clinical Evidence, Cochrane, European Medicines Agency, Medical Journal of Australia (MJA), Medscape, National electronic Library for Medicines, National Guideline Clearing House (NGC), National Health and Medical research Council (NHMRC), National Heath Service Health Technology Assessment Programme (NHS HTA Programme), National Institute for Health and Clinical Excellence (NICE), National Library for Health (NLH), National Prescribing Centre (NPC, MeReC), Pharmaceutical Benefits Advisory Committee (PBAC), Scottish Intercollegiate Guidelines Network (SIGN), Scottish Medicines Consortium (SMC), Therapeutic Goods Administration, US Food and Drug Administration.
An Embase search (1996 to 2007 week 24) was also performed using the following MESH terms:
a. exp Ulcerative Colitis
b. exp INFLIXIMAB
c. a and b combined.
d. “Randomised Controlled Trial”
e. a and d combined.
f. exp evidence based practice or exp evidence based medicine
g. c and f combined.
h. economic evaluation or “cost benefit analysis” or “cost control” or “cost effectiveness analysis” or “cost minimization analysis” or “cost of illness” or “cost utilitiy analysis”
i. c and h combined.
j. exp Adverse Drug Reaction/dt [Drug Therapy]
k. b and j combined.
l. exp Case Control Study or exp Cohort Analysis
m. b and j combined.
n. limit c to (infant or child or preschool child <1 to 6 years> or school child <7 to 12 years> or adolescent <13 to 17 years>).
All of the results were assessed, and abstracts of the selected papers are presented in this document.
Summaries of systematic reviews and guidelines are reproduced verbatim where possible, but may have been edited for conciseness. The abstracts of review articles and clinical studies are taken verbatim from Embase (background information may have been deleted) and are presented chronologically (latest studies first). Full citations are given so that readers may consult the full papers if required.