Infliximab use in patients with Crohn's disease: quality of life, costs and resource use.

Abstract

Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract which primarily affects young adults, with the highest incidence rates reported from Northern Europe, the United Kingdom and North America ranging from 6.9 to 15.6 cases per 100.000 person-years. The course of disease is characterised by episodes of remission and flare-up. The impact on the physical, social, as well as the emotional well-being of patients is substantial and the disease profoundly decreases the quality of life (QoL). The treatment of CD is unsatisfactory, since none of the existing treatments such as aminosalicylates, corticosteroids, immunosuppressive drugs or surgery are curative. Although these treatments have a positive effect on most patients, there is a high incidence of relapse and particularly morbidity from side effects. Infliximab (Remicade), a monoclonal antibody directed against tumour necrosis factor-alpha (TNF-a), was introduced in 1998 and has revolutionised treatment. It is indicated for fistulising CD and the treatment of moderately to severely active luminal CD resistant to conventional therapy. The initial response rates for these indications are 61 to 69% and 58 to 65%, respectively. An infusion of 5 mg/kg infliximab can be given as induction treatment at week 0, 2 and 6, or as maintenance treatment every eight weeks after induction treatment. Maintenance therapy sustains fistula closure, clinical remission and clinical response significantly more than induction treatment only. This implicates an additional therapeutic option for patients previously thought to be refractory to therapy. Although the efficacy of infliximab treatment in CD patients is proven, prescription of infliximab is hampered in daily practice due to its costs (the Netherlands: up to € 14,000 yearly) and the funding system (such as in the Netherlands, Belgium, Canada and the USA). In general, CD has an expensive course of disease, since diagnosis is at an early age and life expectancy is normal. Annual direct medical costs for CD patients are predominantly caused by surgery and other inpatient services, such as hospitalisation, resulting in 81% of the costs, whereas medications only account for 10% of the costs. All other costs are produced by initial diagnostic workups, outpatient services and long-term complications. Annual costs for CD patients per year are difficult to obtain since costs depend on the natural course of the disease. Feagan et al. estimated annual costs varying from US $ 6,277 to $ 37,135 by employing different disease severity groups. Remarkable is the fact that only 2% of the CD patients generate 28.9% of the total costs. Unemployment, disability compensation, compromising of professional career, lost time from work and early retirement are indirect non-medical costs of CD which are difficult to assess but account for high costs to society. An average of 25% of patients with moderate to severe luminal CD in the USA, Europe, Canada and Israel received disability compensation, 39% were unemployed with only 14% of them feeling well enough to work. A Swedish study, which used Swedish national registry data to calculate costs for both ulcerative colitis and CD, reported annual indirect costs at US $ 58.4 million for 40,000 patients, which is a twofold higher than the direct costs. Remission of CD increases employment and is associated with a reduced number of hospitalisations and operations, as well as a normalised QoL. Because infliximab can induce and sustain remission in most patients with refractory and fistulising CD, the most severe type of the disease, this strategy could be cost-effective despite its costs. The aim of this review is to critically appraise the costutility and cost-effectiveness of infliximab in patients with CD by summarising all available evidence with respect to the effect of infliximab on QoL, medical costs and use of resources.