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P572. Adalimumab achieves efficacy in mucosal healing regardless of baseline disease severity in patients with Crohn's disease: Data from EXTEND

W.J. Sandborn1, D. Wolf2, J.-F. Colombel3, J. Panes4, S. Eichner5, A. Iezzi5, Q. Zhou5, A.M. Robinson5, M. Castillo5, R. Thakkar5, 1University of California, San Diego, Division of Gastroenterology, La Jolla, United States, 2Atlanta Gastroenterology Associates, Atlanta, United States, 3Icahn School of Medicine at Mount Sinai, Division of Gastroenterology, New York, United States, 4Hospital Clinic University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain, 5AbbVie Inc, GPRD, North Chicago, United States

Background

Results from the clinical trial EXTEND demonstrated that adalimumab (ADA)-treated patients (pts) with moderately to severely active Crohn's disease (CD) were more likely to achieve mucosal healing (MH) than pts receiving placebo (PBO) [1]. The influence of baseline disease severity on MH is examined.

Methods

In EXTEND, adult pts with CDAI ≥220 to 450 and mucosal ulceration received open-label (OL) ADA 160/80 mg at weeks 0/2. At week 4, pts were stratified by responder status (decrease in CDAI ≥70 points) and randomised to double-blind PBO or ADA (40 mg every other week [eow]) to week 52. Pts experiencing flare or non-response could move to OL eow dosing after week 8, followed by escalation to weekly dosing for continued flare/non-response. Endoscopies were performed at baseline (BL), week 12, time of move to OL eow dosing, if after week 12, and week 52. MH (absence of mucosal ulceration) was assessed at weeks 12 and 52 in pts who had mucosal ulceration at screening. Subgroup analyses by prior anti-TNF use and by disease severity based on baseline CDAI (moderate CD, CDAI ≤300; severe CD, CDAI >300) were performed. Non-responder imputation was used for missing data or that obtained after move to weekly dosing.

Results

Mean BL CDAI, CDEIS, and SES-CD scores were 253.9, 8.9, and 11.0, for pts with moderately active CD, and 365.9, 11.4, and 13.6, for pts with severely active CD, respectively. A greater proportion of ADA-treated than induction ADA only/PBO-treated pts achieved MH at week 12 in both severity subgroups, although the differences were not statistically significant (Table, ADA vs PBO, p = 0.1 moderate CD, p = 0.3 severe CD). Statistically significant differences in MH rates were observed at week 12 in anti-TNF naïve pts with moderate CD treated with ADA compared to induction ADA only/PBO-treated pts (37.5% vs 0, p < 0.05). Significantly more ADA-treated pts than induction ADA only/PBO pts had mucosal healing at week 52 in both severity groups (Table). None of the induction ADA only/PBO-treated pts had MH at week 52. Previous anti-TNF exposure did not show a consistent influence on MH outcomes.

Table: Mucosal healing (MH) in patients with moderately vs severely active CD by visit and prior anti-TNF use
Moderate CD (CDAI ≤300)Severe CD (CDAI >300)
PBOADAPBOADA
MH Week 12, n/N (%)
Overall4/24 (16.7)10/27 (37.0)4/37 (10.8)7/35 (20.0)
Anti-TNF-naive0/86/16 (37.5)*3/18 (16.7)4/16 (25.0)
Anti-TNF-experienced4/16 (25.0)4/11 (36.4)1/19 (5.3)3/19 (15.8)
MH Week 52, n/N (%)
Overall08 (29.6)**07 (20.0)**
Anti-TNF-naive0/84/16 (25.0)0/184/16 (25.0)*
Anti-TNF-experienced0/164/11 (36.4)**0/193/19 (15.8)
ADA, adalimumab; PBO, placebo.
† PBO pts received OL ADA at weeks 0/2.
*p < 0.05, **p ≤0.01 PBO vs ADA, Cochran–Mantel–Haenszel test.

Conclusion

Pts receiving ADA maintenance therapy are more likely to achieve MH at week 52 than PBO-treated patients regardless of baseline disease severity.

1. Rutgeerts P, et al. Gastroenterology 2012; 142: 1102.