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P182. Impact of induction dosing on maintenance outcome with adalimumab in Crohn's disease

J. Colombel1, P. Rutgeerts2, W.J. Sandborn3, W. Reinisch4, E.V. Loftus Jr.5, J. Tang6, P.F. Pollack7, M. Yang7, B. Huang7, J. Chao7, P.M. Mulani7

1Centre Hospitalier Universitaire de Lille, Lille, France; 2University Hospital of Gasthuisberg, Leuven, Belgium; 3University of California, San Diego, La Jolla, CA, United States; 4Medical University of Vienna, Vienna, Austria; 5Mayo Clinic, Rochester, MN, United States; 6Analysis Group, Inc., Boston, MA, United States; 7Abbott Laboratories, Abbott Park, IL, United States

Aim: Two induction regimens of adalimumab are used in Crohn's disease (CD): 160/80 mg at Weeks 0 and 2 and 80/40 mg at Weeks 0 and 2. No comparison of efficacy over the long-term for patients who received 160/80 mg vs. 80/40 mg as induction therapy followed by eow maintenance therapy has been performed.

Materials and Methods: Data were from 2 randomized, double-blinded, placebo-controlled efficacy and safety trials of patients with moderate to severe CD. EXTEND, a 52-week study in patients with mucosal ulceration, used the 160-/80-mg induction regimen. CHARM, a 56-week study for maintenance of clinical remission, used the 80-/40-mg induction regimen. All patients who started with induction dose and were randomized to eow from both trials plus those patients who started with induction dose but were not randomized (ie, dropouts prior to Week 4) were included. Missing Crohn's Disease Activity Index (CDAI) scores were imputed with both non-responder imputation (NRI) and last observation carried forward (LOCF). Remission (CDAI < 150) and hospitalization were compared between patients starting with 160-/80-mg and those starting with 80/40 mg. To incorporate the correlation between visits for a patient, a logistic regression with the patient-level random intercept using all the time points after Week 4 was constructed to compare likelihood of remission, controlling for baseline CDAI, fistula, prior use of an anti-tumor necrosis factor therapy, concomitant medications, CD duration, and other factors.

Results: In total, 70 patients in the 160-/80-mg group were compared with 336 patients in the 80-/40-mg group. Baseline characteristics for the 2 groups were similar except for greater rates of rectal/anal CD in the 160-/80-mg arm and greater use of concomitant steroids in the 80-/40-mg arm. Compared with the 80-/40-mg group, the 160-/80-mg group had a greater percentage of time in remission from Week 0–52 (36% vs. 25%; p < 0.05, NRI), significantly fewer hospitalizations per patient (0.09 vs. 0.23; p < 0.05), and significantly fewer CD-related hospitalizations (0.07 vs. 0.18; p < 0.05). Patients in the 160-/80-mg group were significantly more likely to be in remission during Weeks 4 to 52 than were patients in the 80-/40-mg group after adjusting for baseline characteristics (adjusted odds ratio = 4.8; p < 0.001). Similar results were consistently shown using the LOCF for remission analysis. In safety analyses, it did not appear that the 160-/80-mg dose led to a higher rate of AEs.

Conclusion: The 160-/80-mg induction regimen of adalimumab was associated with a greater likelihood of remission, more time in remission, and fewer hospitalizations during eow maintenance therapy compared with the 80-/40-mg regimen.