A retrospective, observational study to examine the effect of early tumor necrosis factor inhibitor use on rates of surgery for Crohn's disease in Japan.

Abstract

Background: Crohn's disease (CD) is an incurable inflammatory condition that often requires multiple surgeries, negatively impacting quality of life. As such, treatment strategies that aim to prevent damage to the bowel and reduce the burden of surgeries for patients with CD are important. This retrospective, long-term, observational study investigated whether tumor necrosis factor inhibitor (TNFi) treatment was associated with decreased rates of abdominal surgery in Japanese patients with CD.

Methods: Patients were divided into two groups based on prior TNFi therapy (TNFi-treated and TNFi-untreated). Outcomes assessed included surgery rate, cumulative surgery-free survival rate, and time to surgery. For surgery rate, treatment groups were compared through estimation of an odds ratio (OR) with 95% confidence intervals (CIs). Cumulative surgery-free survival rate and time to surgery was calculated using Kaplan-Meier methodology and compared using log-rank tests. The primary analysis compared outcomes between the TNFi-treated and TNFi-untreated groups. Subgroup analyses compared outcomes between two subgroups of the TNFi-treated group (infliximab-treated vs. adalimumab-treated) and the TNFi-untreated group.

Results: Overall, 124 patients with CD were included in the analysis (TNFi-treated: N = 86; TNFi-untreated: N = 38). Of those patients who received TNFi treatment, 62 received infliximab and 24 received adalimumab. The median (range) observation period in the TNFi-treated and TNFi-untreated groups was 4.62 (0.41-13.75) years and 8.13 (0.08-30.25) years, respectively. Median time to surgery was 3 years in the TNFi-untreated group and 6.58 years in the TNFi-treated group. A significantly lower proportion of patients in the TNFi-treated group required surgery (3/86) compared with those in the TNFi-untreated group (17/38; OR [CI]: 0.0446 [0.0120-0.1667]; P < 0.0001). Cumulative surgery-free survival rates were significantly higher in the TNFi-treated group versus the TNFi-untreated group (P < 0.0001). Compared with the TNFi-untreated group, the proportion of patients who required surgery was significantly lower with both infliximab (1/62; OR [CI]: 0.0203 [0.0025-0.1616]; P = 0.0002) and adalimumab (2/24; OR [CI]: 0.1123 [0.0231-0.5466]; P = 0.0068). Cumulative surgery-free survival rates were significantly higher in the infliximab-treated group versus the TNFi-untreated group (P < 0.0001).

Conclusions: Introduction of TNFis for the treatment of CD may lead to a reduction in surgery rates and prolong time to surgery.