P496 Adalimumab treatment reduces extraintestinal manifestations in patients with moderate-to-severe Crohn’s disease: a pooled analysis
E. J. Louis*1, R. Löfberg2, W. Reinisch3, D. Schwartz4, J.-F. Maa5, S. Berg5, B. Huang5, A. W. Wang5, A. M. Robinson5, B. Pappalardo5
1University of Liège and CHU, Liège, Belgium, 2Karolinska Institutet and IBD Unit, Sophiahemmet, Stockholm, Sweden, 3Medical University of Vienna, Vienna, Austria, 4Vanderbilt University Medical Centre, Nashville, United States, 5AbbVie Inc., North Chicago, Illinois, United States
Extraintestinal manifestations (EIMs) are present in up to 40% of patients (pts) with Crohn’s disease (CD), and are associated with significant morbidity and impaired quality of life.1 Data were pooled from 10 adalimumab (ADA) CD trials to evaluate the effect of ADA therapy on resolution of EIMs.
Pooled EIM data from ADA CD trials were evaluated in pts randomised to placebo (PBO) or ADA therapy during open-label (OL) or double-blind induction and maintenance phases.2,3,4,5,6,7,8,9 The ADA group included all pts randomised to ADA (including those who received OL rescue therapy). Pts who received PBO induction or who received OL ADA induction before randomisation to PBO were classified as PBO. Data from PBO pts who received OL ADA rescue therapy were censored from that point. Assessment of EIMs was based on question #4 of the CD Activity Index (CDAI), which evaluates EIM categories: musculoskeletal (arthritis/arthralgia), ocular (iritis/uveitis), or cutaneous (erythema nodosum, pyoderma gangrenosum or aphtous stomatitis). Resolution of EIMs in pts with EIMs at baseline (BL) was evaluated at weeks (wk) 26 and 52 (or the time points closest to these wk in each study). Wk 4 outcomes were not analysed to limit the effects of ADA exposure in PBO patients who received OL ADA induction. Median time to resolution of any EIM or specific EIMs (musculoskeletal, ocular, and cutaneous) was calculated. Data reported are as observed for ADA and PBO pts up to the time they were censored.
At BL, 51% (296/585) of PBO and 54% (1139/2 098) of ADA pts had EIMs; musculoskeletal (48% vs 52%), cutaneous (4% vs 6%), and ocular (1% each). Of pts who had any EIM or musculoskeletal EIMs at BL, resolution occurred in a numerically greater proportion of ADA vs PBO pts at wk 26 and 52 (Table 1). Median time to resolution of any EIM, musculoskeletal, and cutaneous EIMs were significantly shorter in pts receiving ADA vs PBO (Table 1 and Figure 1).
In pts with moderately to severely active CD, ADA was effective in resolving any EIM and musculoskeletal EIMs at wk 26 and 52. Resolution of EIMs was more rapid in ADA vs PBO pts.
Table 1 Pooled analysis of proportion of patients with resolution of EIMs and median time to resolution of EIMs in adalimumab Crohn’s disease trials (as observed)
Figure 1. Time to resolution of ANY EIM.
1Ardizzone DLD 2008
2Hanauer Gastroenterol 2006
3Sandborn Gut 2007
4Colombel Gastroenterol 2007
5Rutgeerts Gastroenterol 2012
6Sandborn Ann Intern Med 2007
7Löfberg IBD 2012
8Watanabe JCC 2012
9Hyams Gastroenterol 2012