December's Paper of the Month looks at the results of the LIR!C Trial comparing treatments for ileocecal Crohn’s disease.
Cost-effectiveness of laparoscopic ileocaecal resection versus infliximab treatment of terminal ileitis in Crohn’s disease: the LIR!C Trial. E Joline de Groof, Toer W Stevens, Emma J Eshuis, Tjibbe J Gardenbroek, Judith E Bosmans, Hanneke van Dongen, Bregje Mol, Christianne J Buskens, Pieter C F Stokkers, Ailsa Hart, Geert R D’Haens, Willem A Bemelman, Cyriel Y Ponsioen, on behalf of the LIR!C study group
What is known on the subject
Ileocecal Crohn’s disease is common, affecting approximately a third of patients. In these patients, treatment is started with conventional immunomodulators (glucocorticosteroids, thiopurines, methotrexate). When these fail, and patients require further treatment, both biologics and surgery can be therapeutic options. The L!RIC trial [1] is a randomised controlled trial that compared quality of life at one year between and laparoscopic ileo-caecal resection and infliximab. 73 patients were allocated to surgery and 70 were allocated to infliximab.
The trial showed similar results in terms of primary outcomes: IBDQ score and an inflammatory bowel disease specific QoL questionnaire. As for secondary outcomes, the number of days when patients were unable to take part in social life and number of unscheduled admissions were similar between groups. Clavien Dindo grade IIIa or worse complications occurred in 4 patients in the surgery group. Serious treatment adverse effects occurred in 2 patients in the infliximab group. Importantly, at a median follow up of 4 years, 37% of the patients in the infliximab group had undergone surgery and 26% of the patients in the surgery group received infliximab.
The authors concluded that
"Laparoscopic resection in patients with limited (diseased terminal ileum <40 cm), non-stricturing, ileocaecal Crohn’s disease in whom conventional therapy has failed could be considered a reasonable alternative to infliximab therapy."
What this study adds
The LIR!C trial assessed difference in QoL as its primary outcome. Given the conclusion that surgery is a reasonable alternative to biologic therapy, and that biologic therapy is often continued for prolonged periods, the authors hypothesized that surgery would lead to cost savings [2]. To test this hypothesis, patients recruited to the trial were followed up further and assessed with cost effectiveness and cost utility analyses. Cost-effectiveness analysis was expressed as a function of the IBDQ and cost-utility expressed in quality adjusted life years (QALYs). These were used to analyse costs associated with either surgery or with biologic treatment. Costs considered were Crohn’s disease-related direct healthcare, other healthcare costs, travel costs and lost productivity costs.
In the year after the start of either biologic therapy or surgery, the direct costs of surgery were significantly lower than infliximab, although absenteeism costs were significantly higher. As time went on, the continuing expense of infliximab made surgery cost-effective in this context. Patients in the resection group had significantly more QALYs over 12 months compared with patients in the infliximab group.
Sensitivity analyses were performed for costs of infliximab using the reference cost of a biosimilar and not the patented drug, and also for a scenario with different age of onset to account for differing severity of disease in patients diagnosed at a younger age. The use of a biosimilar drug, being cheaper, showed that surgery became cost effective at 14 months (vs 12 months with infliximab).
Implications for colorectal practice
The decision to perform surgery or to use biologics in patients with limited ileocecal Crohn's disease failing conventional therapy has different cost considerations. These are not only direct but also indirect costs that can continue to accrue over time. This paper has shown that surgery is cost effective at 12 months. In the context of continued use of infliximab, the cost benefit of surgery will tend to increase. This information will hopefully be used to inform decision making in the future, optimising resources to provide the best possible treatment for our patients.
References
- Y Ponsioen, H. C. et al. Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn’s disease: a randomised controlled, open-label, multicentre trial. (2017). doi:10.1016/S2468-1253(17)30248-0
- De groof, E. J. et al. Cost-effectiveness of laparoscopic ileocaecal resection versus infliximab treatment of terminal ileitis in Crohn’s disease: The LIR!C Trial. Gut 68, 1774–1780 (2019)