Volume 142, Issue 5, Pages 1102-1111.e2 (May 2012) Adalimumab Induces and Maintains Mucosal Healing in Patients With Crohn's Disease: Data From the EXTEND Trial  Paul Rutgeerts, Gert Van Assche, William J. Sandborn, Douglas C. Wolf, Karel Geboes, Jean–Frédéric Colombel, Walter Reinisch, Ashish Kumar, Andreas Lazar, Anne Camez, Kathleen G. Lomax, Paul F. Pollack, Geert D'Haens  Gastroenterology  Volume 142, Issue 5, Pages 1102-1111.e2 (May 2012) DOI: 10.1053/j.gastro.2012.01.035 Copyright © 2012 AGA Institute Terms and Conditions

Figure 1 EXTEND study design. The primary efficacy end point was complete mucosal healing (ie, absence of mucosal ulceration) as determined by the review committee's visual assessment of the ileocolonoscopies at week 12. Patients who continued on blinded therapy for the full duration of the trial or who switched to open-label therapy before week 12 had 3 ileocolonoscopies (baseline, week 12/switch to open label, and week 52/termination). Patients who remained on their randomized treatment until week 12 and subsequently switched to open-label therapy had 4 ileocolonoscopies (baseline, week 12, switch to open label every other week [eow], and week 52/termination). aAdalimumab induction only with placebo maintenance; reinitiation of adalimumab for flare/nonresponse. Gastroenterology 2012 142, 1102-1111.e2DOI: (10.1053/j.gastro.2012.01.035) Copyright © 2012 AGA Institute Terms and Conditions

Figure 2 Efficacy of adalimumab for sustained mucosal healing. (A) Mucosal healing results at week 12 and week 52 per the review committee's assessment of the absence of mucosal ulceration; all analyses of complete mucosal healing included only patients with ulceration at screening as judged by the review committee. Patients who switched to open-label adalimumab between week 8 and week 12 underwent ileocolonoscopy before receiving their first doses of open-label therapy, and the results were carried forward to week 12 for the primary analysis. Nonresponder imputation was used for missing information on mucosal ulceration at weeks 12 and 52, whereby patients with missing data for mucosal healing were considered to have mucosal ulceration. For the analysis at week 52, patients who discontinued or switched to open-label treatment before week 52 were considered as having mucosal ulceration at week 52. Treatment displayed is original treatment at randomization. (B) Mucosal healing rates at week 12 and week 52 by median CDEIS score (CDEIS ≤9 or >9) at baseline. (C) CDEIS remission, defined as a CDEIS score of ≤4, at weeks 12 and 52. (D) CDEIS response, defined as a decrease in CDEIS >75% from baseline, at weeks 12 and 52. (E) CDAI remission using nonresponder imputation for missing clinical remission and for patients who entered the open-label phase at week 52. aP value from Cochran–Mantel–Haenszel test with CR-70 status at week 4 as the stratification factor. bComplete mucosal healing at week 12 was the primary end point. Four patients randomized to placebo and 2 patients randomized to continuous adalimumab every other week were excluded from the analyses of mucosal healing owing to absence of mucosal ulceration at screening (as judged by the review committee). cPer protocol represents all intent-to-treat (ITT) patients who did not have a significant protocol deviation; 6 ITT patients (1 with continuous adalimumab, 5 with induction only/placebo) were excluded: one adalimumab-treated patient did not meet diagnosis guidelines for ileocolonic CD, 2 patients in the induction-only/placebo group received the wrong dosage, 2 patients in the induction-only/placebo group had a baseline CDAI score >450, and one patient in the induction only/placebo group lacked documentation of the required degree of mucosal ulceration. dITT = 129 randomized patients; treatment displayed is original treatment at randomization. eITT = 129 randomized patients, irrespective of the review committee's assessment of the presence of mucosal ulceration at screening. Gastroenterology 2012 142, 1102-1111.e2DOI: (10.1053/j.gastro.2012.01.035) Copyright © 2012 AGA Institute Terms and Conditions

Supplementary Figure S1 EXTEND patient disposition. A total of 135 patients entered the induction phase and received adalimumab 160 mg at baseline/week 0 and 80 mg at week 2; 129 patients were randomized at week 4 (65 to induction only/placebo and 64 to continuous adalimumab). Eighteen patients (28.1%) randomized to adalimumab had their dosage increased to adalimumab 40 mg weekly. Five patients (8%) randomized to induction only/placebo and 10 patients (16%) randomized to continuous adalimumab discontinued from the study during the double-blind phase. eow, every other week. Gastroenterology 2012 142, 1102-1111.e2DOI: (10.1053/j.gastro.2012.01.035) Copyright © 2012 AGA Institute Terms and Conditions