Early anti-TNF/immunomodulator therapy is associated with better long-term clinical outcomes in Asian patients with Crohn's disease with poor prognostic factors

Abstract

Although early treatment of Crohn's disease (CD) patients with anti-tumor necrosis factor (TNF) agents or immunomodulators (IMs) may improve long-term outcomes, especially those with poor prognostic factors, their effectiveness in Asians remains unclear. In this study, Korean patients with CD naïve to both intestinal surgery and intestinal complications, and with at least two risk factors for progression (diagnosis at age <40 years, systemic corticosteroid treatment <3 months after diagnosis, and perianal fistula at diagnosis) were retrospectively analyzed. Patients were classified into those who started anti-TNFs, or IMs but not anti-TNFs, within 2 years of diagnosis, and those who started anti-TNFs and/or IMs later. Their probabilities of intestinal surgery and intestinal complications were compared. A total of 670 patients were enrolled, 79 in the early anti-TNF, 286 in the early IM, and 305 in the late treatment group. Kaplan-Meier analysis with the log-rank test showed that from starting anti-TNFs/IMs, times to intestinal surgery (P < 0.001), stricturing complications (P = 0.002), and penetrating complications (P < 0.001) were significantly longer in the early anti-TNF/IM groups than in the late treatment group. Multivariate Cox regression analysis showed that, from starting anti-TNFs/IMs, late anti-TNF/IM treatment was independently associated with higher risks of intestinal surgery (adjusted hazard ratio [aHR] 2.321, 95% confidence interval [CI] 1.503-3.584, P < 0.001), behavioral progression (aHR 2.001, 95% CI 1.449-2.763, P < 0.001), stricturing complications (aHR 1.736, 95% CI 1.209-2.493, P = 0.003), and penetrating complications (aHR 3.315, 95% CI 2.094-5.249, P < 0.001) than early treatment. In conclusion, treatment of Asian CD patients having poor prognostic factors with anti-TNFs/IMs within 2 years of diagnosis is associated with better clinical outcomes than later treatment.

Fig 1. Patient flow diagram.

Fig 2. The Kaplan-Meier survival analysis for key outcome variables from starting anti-TNFs/IMs treatment.

(A) Cumulative probabilities of intestinal surgery (the early anti-TNF/IM groups vs. the late therapy group, P < 0.001), (B) Cumulative probabilities of behavioral progression (the early anti-TNF/IM groups vs. the late therapy group, P < 0.001), (C) Cumulative probabilities of developing stricturing complication (the early anti-TNF/IM groups vs. the late therapy group, P = 0.002), and (D) Cumulative probabilities of developing penetrating complication (the early anti-TNF/IM groups vs. the late therapy group, P < 0.001) from starting anti-TNFs/IMs.