P381 Adalimumab efficacy and safety by disease duration: analysis of pooled studies of Crohn's disease

Abstract

Background: Adalimumab (ADA) has been shown in one post hoc analysis to be effective in pts with moderately to severely active Crohn's disease (CD) with <2 yrs disease duration [1]. In this analysis, we pooled data from 9 CD clinical studies of ADA to assess the impact of disease duration on clinical outcomes in ADA-treated pts. Methods: Pts receiving double blind (DB) or open label (OL) ADA induction (80/40mg or 160/80mg ADA at week [wk] 0/2) followed by DB ADA 40mg every other wk (EOW)/every wk (EW) or OL ADA 40mg EOW/EW were included in the analysis. Pts randomized to PBO were excluded. Pts were analysed by <2, 2–5, >5 years disease duration at BL. Remission (CDAI <150 or HBI<5) rates were analysed within disease duration groups from 4–52 wks using Cochrane-Armitage test. A modified non-responder imputation was used whereby pts who moved to OL EOW or EW ADA for flare/non-response were reported according to their observed response. AE rates were reported by BL disease duration. Results: Of 2207 pts included in this analysis, approximately 60% were female. BL disease duration groups included 270 (<2 yrs), 435 (2–5 yrs), and 1502 (>5 yrs) pts. Mean CDAI and HBI ranged from 292.3–304.3 and 10.7–11, respectively, across disease duration groups. Significant differences in BL fistula presence, BL corticosteroid (CS) use and prior α-TNF use were observed between disease duration groups (fistula: 27 [10.0%], 73 [16.8%], 278 [18.5%], [p=0.003]; CS: 84 [31.1%], 86 [19.8%], 332 [22.1%], [p=0.001]; α-TNF use: 33 [12.2%], 108 [24.8%], 389 [25.9%], [p<0.001] for <2, 2–5, >5 yrs disease duration groups, respectively). Significant differences between disease duration groups in remission rates occurred as early as wk 4 and sustained for up to wk 52 (Figure 1). Overall rate of AEs, SAEs, AEs leading to discontinuation and malignancies were similar between disease duration groups. Serious infection rate was lower in the <2 yrs disease duration group vs 2–5 yrs and >5 yrs groups (4.2 vs 8.7 and 8.3/100PY). In the >5 yrs BL disease duration group, 2 deaths occurred that have been previously reported [2]. Figure 1. Proportion of patients with remission (CDAI <150 or HBI <5) by BL disease duration. Conclusions: In 9 CD clinical studies, ADA-treated pts with shorter disease duration achieved a better clinical benefit than pts with longer disease duration. Overall safety of ADA was consistent between disease duration groups.