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P137. Effect of concomitant immunomodulator use on the efficacy of adalimumab in Crohn's disease patients stratified by prior anti-TNF use

S. Vermeire1, J. Colombel2, A.M. Robinson3, B. Huang3, R.B. Thakkar3, P.F. Pollack3

1Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium; 2Centre Hospitalier Universitaire de Lille, Lille, France; 3Abbott, Abbott Park, IL, United States

Aim: The SONIC study [1] showed superior remission rates for combination infliximab plus azathioprine treatment (versus monotherapy with either agent) in patients naïve to anti-tumor necrosis factor (TNF) agents and immunomodulators (IMMs). A subanalysis of CHARM [2] showed no influence of combination IMM use on remission rates with adalimumab; however, CHARM enrolled a population with longer Crohn's disease (CD) duration and included patients exposed to IMMs/anti-TNFs. In order to evaluate whether previous anti-TNF use affected the influence of IMM use, 1-year remission rates with adalimumab 40 mg every other week (eow) therapy were determined in patients with moderate to severe CD stratified by prior anti-TNF use.

Materials and Methods: Data from 2 randomized, blinded clinical trials of adalimumab (EXTEND, CHARM) in patients with moderate to severe CD were pooled and analyzed. In EXTEND, all patients (N = 135) received open-label adalimumab 160/80 mg at Weeks 0/2; 129 patients were randomized at Week 4 to adalimumab 40 mg eow (n = 64) or placebo (n = 65). In CHARM, all patients (N = 854) received open-label adalimumab 80/40 mg at Weeks 0/2; 778 patients were randomized at Week 4 to adalimumab 40 mg eow (n = 260), adalimumab 40 mg weekly (n = 257), or placebo (n = 261). Changes in baseline concomitant CD-related medications were not allowed, with the exception of corticosteroids, which could be tapered at the investigator's discretion. Rates of clinical remission (Crohn's Disease Activity Index [CDAI] <150) at 1-year with and without baseline IMM use were calculated for placebo and adalimumab 40 mg eow patients in the intent-to-treat (ITT) population, which included all randomized patients, stratified by prior anti-TNF exposure. Clinical remission rates were compared using the Cochran-Mantel-Haenszel test, adjusting for baseline disease duration category (<2, 2 to <5, and ≥5 years).

Results: Clinical remission rates and median CD duration in each group are shown (Table). The median CD duration was longer in TNF-exposed groups versus TNF-naïve groups. For adalimumab-treated patients with prior anti-TNF exposure, remission rates were not significantly different in patients receiving concomitant IMMs versus those not receiving IMMs (28.8% vs. 18.1%; P = 0.171). For adalimumab-treated patients without prior anti-TNF use, no significant differences in remission rates were observed between patients receiving concomitant IMMs versus those not receiving IMMs (33.9% vs. 38.2%; P = 0.459).

Conclusion: Use of concomitant IMMs did not influence the rates of clinical remission achieved at 1-year with adalimumab therapy in patients with moderate to severe CD when analyzed by prior anti-TNF exposure. The finding of numerically lower remission rates in patients with previous anti-TNF exposure may be related, at least in part, to longer disease duration and warrants further exploration.

Table. One-Year Clinical Remission Ratesa
Prior Anti-TNF UseBaseline IMM UseMedian Disease Duration, YearsPlacebo
n/N (%)
ADA 40 mg eow
n/N (%)
YesYes8.843/84 (3.6)23/80 (28.8)**
YesNo9.788/83 (9.6)15/83 (18.1)*
NoYes5.8112/74 (16.2)20/59 (33.9)*
NoNo7.3610/85 (11.8)39/102 (38.2)**
*P < 0.05, **P < 0.001 for placebo vs. ADA.a1-year defined as Week 52 for EXTEND and Week 56 for CHARM

1. Colombel JF et al. Gastro. 2007;132(1):52–65.

2. Hanauer SB et al. Am J Gastroenterol. 2006;101(9 Suppl):S457.