In the era of biologics’ ascendancy, a Dutch-British randomized study found that laparoscopic resection was significantly more cost-effective at 1 year than infliximab (Remicade) in patients with refractory Crohn’s disease, and should therefore be considered a valid alternative.
In the prospective comparison, Crohn’s-related healthcare costs were €8,931 lower with laparoscopic ileocecal resection than with the tumor necrosis factor inhibitor infliximab for disease of the terminal ileum that is unresponsive to conventional therapy (95% CI -€12,087 to -€5,097), Willem A. Bemelman, MD, of Amsterdam University Medical Center, and colleagues reported.
And total mean societal costs in the resection group were €5,729 lower (95% CI –€10,606 to -€172), they wrote in Gut. (The Euro is currently worth $1.14 in U.S. dollars.)
“This is an important finding for clinical practice, because with the introduction of biologics, there has been a major shift in IBD-related direct healthcare costs from hospitalization and surgery towards medical treatment with biologics,” the team said.
The multicenter LIR!C trial was conducted from May 2008 to October 2015 at 28 centers in the Netherlands and one in the U.K. Adult patients with Crohn’s disease of the terminal ileum for whom >3 months of immunomodulator or steroid treatment had failed without signs of a critical stricture were eligible for inclusion, while those with prior ileocecal resection, an affected segment >40 cm, abdominal abscesses, or fluid collections were not included.
The study’s economic evaluation covered direct and other healthcare costs, travel expenses, and lost productivity due to absenteeism. The analysis also measured health-related quality of life and quality-adjusted life years (QALYs). Patients were assessed at weeks 2 and 6 as well as at months 3, 6, 9, and 12.
Overall, 143 patients were randomized — 73 to laparoscopic surgery and 70 to infliximab. The cohort was 32.9% male and had a median age at randomization of 27 and a median disease duration of 14 months.
Medication and sick leave costs, however, proved higher for the surgical arm. The mean differences were €54 (95% CI €36-€77) and €2,596 (95% CI €579-€4,719), respectively. These were offset by insignificantly lower primary care and total societal costs in the resection group.
After 12 months, the mean Inflammatory Bowel Disease Questionnaire (IBDQ) score was 180.8 in the resection group and 173.5 in the infliximab group, a statistically nonsignificant difference, the researchers reported.
The probability of resection’s cost-effectiveness versus infliximab was 0.96 at a willingness to pay (WTP) of €0 per QALY gained and per point improvement in IBDQ score. This probability increased to 0.98 at a WTP of €20,000 per QALY gained and to 0.99 at a WTP of €500 per point of improvement in IBDQ score.
In terms of clinical outcomes, the average utility score in the resection group was lower during the first weeks of the trial. After 13 weeks, however, the utility scores in the resection arm were higher than in the infliximab arm. The difference in mean utility scores between the two groups reached a maximum of 0.10 after 26 weeks and remained relatively stable thereafter. In addition, the mean number of QALYs after 12 months was significantly larger with resection than with infliximab: 0.81 versus 0.74 (95% CI 0.01-0.12).
Looking at laparoscopic resection versus today’s cheaper biosimilars, the investigators found that societal costs were nonsignificantly higher for resection after 1 year. But the break-even point, after which biosimilars would rapidly become more expensive, was estimated at 14 months — only 8 weeks after 1-year follow-up, the team found.
The authors noted that previous economic evaluations mainly compared biologic with conventional treatment and focused on the cost-effectiveness of long-term infliximab maintenance therapy. A systematic review found that even with a high WTP of $100,000 per QALY, only two out of six studies concluded that infliximab maintenance therapy was cost-effective after 1 year versus conventional treatment. In another four studies assessing budget impact, infliximab was cost-saving in only one.
Bemelman and co-authors pointed to the need for data on the evolution of costs beyond 12 months, especially since biologic maintenance therapy may be continued over the longer term.
Asked for his perspective, Alex Greenstein, MD, of the Icahn School of Medicine at Mount Sinai in New York City, called the study “definitely intriguing” and said it adds to the literature suggesting that surgery is a reasonable first-line therapy for refractory Crohn’s disease. “But it is difficult to translate the direct costs to the United States setting, where many surgical patients are also put quite aggressively on prophylactic biologics after surgery, so the difference may not be as clear-cut here,” he said.
Greenstein also noted that had the study been started later, the impact of less expensive biosimilar drugs may have brought the resection-biologic costs closer together: “An important take-home message of the study is that QALYs were better in the resection group and that there were minimal complications,” he said.
Study limitations, Bemelman and co-authors noted, included the inclusion period of 7 years, which might increase the risk of selection bias. In addition, as noted, the trial began in 2008 when less expensive biosimilars were not yet available. In a sensitivity analysis based on biosimilars costing 40-60% less than the originator drug, the difference in societal costs changed nonsignificantly, with resection being slightly more costly than the biosimilar.
Another limitation, the team said, was that the economic evaluation was based on Dutch standard pricing to calculate costs, and even though the Dutch healthcare system is comparable to that of most Western European countries, infliximab reimbursement criteria and costs may vary considerably and might not be generalizable to all countries.
This study was supported by a grant from the Netherlands Organisation for Health Research and Development.
De Groof reported having no competing interests; other co-authors reported financial relationships with Dr. Falk Pharma, AbbVie, GSK, Ferring, MSD, Ablynx, Amakem, AM Pharma, Avaxia, Biogen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Celltrion, Cosmo, Covidien/Medtronics, enGene, Galapagos, Genentech/Roche, Gilead, GlaxoSmithKline, Hospira, Immunic, Johnson & Johnson, Lycera, Medimetrics, Millennium/Takeda, Mitsubishi Pharma, Merck Sharp & Dome, Mundipharma, Novo Nordisk, Otsuka, Pfizer, Prometheus laboratories/Nestlé, Protagonist, Receptos, Robarts Clinical Trials Inc., Salix, Sandoz, Setpoint, Shire, Teva, TiGenix, Tillotts, TopiVert, Versant, Vifor, Norgine, Shire, and Tillotts.
Greenstein reported having no competing interests relevant to his comments.