time from the CD diagnosis was 5 years; 46% of pts had ileocolonic location of disease;68% had inflammatory (B1) disease behavior; 30% had prior resections. Over 7 years, 117pts completed, while 478 discontinued (36% due to AEs; 28% due to pt decision; 17% dueto no improvement/disease deterioration). Discontinuation rates were 29.2%, 13.6%, 16.1%,7.9%, 5.0%, 4.5% and 3.9% during years 1 - 7, respectively. Over 71% of pts were exposedto CZP for >1 year; the average number of CZP injections was 41. No new safety signalswere identified during this study. The most common AE was CD exacerbation (30%); mostcommon OI was herpes simplex (3.4%). The observed annual remission rates ranged from68% - 76% (Year 1 to 7, table). The remission rates analyzed by LOCF and NRI methodswere 58% and 45% at year 1, 56% and 26% at year 3 and 55% and 13% at year 7,respectively. FC levels had no trends toward change; CRP levels were relatively stable. Thegeometric mean CZP plasma concentrations ranged from 6 - 10 ug/mL up to year 6; CZPconcentrations were typically lower in pts who were anti-CZP antibody positive vs. negativethroughout the study (e.g. 3μg/ml vs. 9μg/ml at Wk 54, 3μg/ml vs. 10μg/ml at Wk 210,respectively). Conclusions: The P3 study demonstrates that the long-term safety of CZP isconsistent with short-term studies.[1, 2] Additionally, the observed rates of clinical remissionwere sustainable for 7 years.PRECiSE3 Remission Rates Over 7 Years, observed cases

*Year 0=end of the qualifying study and beginning of the OLE;†Percent of continuingpatients with HBI ≤4. CI, confidence interval. References: 1.Sandborn et al. N Engl J Med.2007;357:228-38 2.Schreiber et al. N Engl J Med. 2007;357:239-50.

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Adalimumab Achieves Efficacy in Mucosal Healing Regardless of BaselineDisease Severity in Patients With Crohn's Disease: Data From EXTENDWilliam Sandborn, Douglas C. Wolf, Jean-Frederic Colombel, Julian Panes, SamanthaEichner, Annalisa Iezzi, Qian Zhou, Anne Robinson, Majin Castillo, Roopal Thakkar

Background: Results from the clinical trial EXTEND demonstrated that adalimumab (ADA)-treated patients (pts) with moderately to severely active Crohn's disease (CD) were morelikely to achieve mucosal healing (MH) than pts receiving placebo (PBO)1. The influenceof 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 weeks0/2. At week 4, pts were stratified by responder status (decrease in CDAI ≥ 70 points) andrandomized to double-blind PBO or ADA (40 mg every other week [eow]) to week 52. Ptsexperiencing flare or non-response could move to OL eow dosing after week 8, followedby escalation to weekly dosing for continued flare/non-response. Endoscopies were performedat 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 hadmucosal ulceration at screening. Subgroup analyses by prior anti-TNF use and by diseaseseverity based on baseline CDAI (moderate CD, CDAI ≤ 300; severe CD, CDAI > 300) wereperformed. Non-responder imputation was used for missing data or that obtained after moveto 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 severelyactive 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 differenceswere not statistically significant (Table, ADA vs PBO, p=0.1 moderate CD, p=0.3 severeCD). Statistically significant differences in MH rates were observed at week 12 in anti-TNFNaive 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 ADAonly/PBO pts had mucosal healing at week 52 in both severity groups (Table). None of theinduction ADA only/PBO-treated pts had MH at week 52. Previous anti-TNF exposure didnot show a consistent influence on MH outcomes. Conclusion: Pts receiving ADA mainte-nance therapy are more likely to achieve MH at week 52 than PBO-treated patients regardlessof baseline disease severity. Reference: 1. Rutgeerts P, et al. Gastroenterol. 2012; 142:1102.MH in patients with moderately vs severely active CD by visit and prior anti-TNF use

†PBO pts received OL ADA at weeks 0/2; *p<0.05; **p≤0.01 PBO vs ADA Cochran-Mantel-Haenszel test

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Mo1220

Patient-Reported Symptom Measures Differ in Their Association With MucosalHealing in Adults With Moderately to Severely Active Ulcerative Colitis:Results From ULTRA 1 and 2Jean-Frederic Colombel, William Sandborn, Walter Reinisch, Anne Robinson, WenruiWang, Bidan Huang, Andreas Lazar, Roopal Thakkar

Background: The efficacy of adalimumab (ADA) for the induction and maintenance ofclinical remission and mucosal healing (MH) in adults with moderate-to-severe ulcerativecolitis (UC) has been demonstrated in the randomized double-blind (DB) placebo (PBO)-controlled trials ULTRA 11 and ULTRA 22. Clinical symptoms may serve as measures ofresponse to treatment, but may not accurately reflect MH status. This post-hoc analysisevaluated the association of the Mayo score components rectal bleeding subscore (RBS) andstool frequency subscore (SFS) with endoscopy subscore (ES) in the 52-week (wk) studiesULTRA 1 and ULTRA 2. Methods: In ULTRA 1 and ULTRA 2, patients (pts) with a Mayoscore of 6-12 and ES ≥ 2 were randomized to PBO or ADA (160/80 mg or 80/40 mg,ULTRA 1 only) at wks 0/2 followed by PBO or 40 mg ADA every other wk (eow). Pts inULTRA 1 received open-label (OL) ADA from wks 8 or 12 to wk 52. Pts could move toweekly ADA (after OL eow ADA in ULTRA 2) for inadequate response. RBS and SFS wereassigned using the worst values of the 3 days prior to each study visit from pt diaries. RBS=0 indicated no visible blood in stool; SFS=0 indicated "normal" stool frequency for that pt.All data (DB or OL) from ADA-160/80mg-treated pts who had subscores at wks 8, 32, and52 were used to assess the association of RBS and SFS values of 0 and MH (ES=0-1 or ES=0) at each visit using the parameters sensitivity (sens; probability that RBS/SFS=0 when MH=yes), specificity (spec; probability that RBS/SFS>0 when MH=no), positive predictive value(PPV; probability that MH=yes when RBS/SFS=0), and negative predictive value (NPV;probability that MH=no when RBS/SFS>0). Results: Of 470 ADA-160/80mg-treated pts,145 had subscores at each visit. Sens, spec, PPV, and NPV analyses (Table) showed thatRBS=0 was likely (>75% of the time) when MH was present (ES= 0-1 or ES=0), whilenormal SFS was less frequent (~25% of the time). This relationship did not change withtime: among pts with MH (ES=0-1) at all 3 visits, a substantially higher proportion hadRBS=0 (80.4%, 82.1%, and 89.3% at wks 8, 32, and 52, respectively) compared with SFS=0 (28.6%, 26.8%, and 33.9%). Conclusion: Patient-reported typical symptoms of UC differedin their association with MH. Absence of rectal bleeding was associated with MH, whereasstool frequency may remain elevated even in pts with sustained MH. RBS may be a morereliable indicator of MH than SFS. References 1. Reinisch W et al. Gut 2011;60:780-7. 2.Sandborn WJ et al. Gastroenterology 2012;142:257-65Association of patient-reported rectal bleeding and stool frequency subscores with mucosalhealing (endoscopy subscore of 0-1 or 0) in adalimumab 160/80 mg treated pts withsubscores at all 3 time points (n=145)

Mo1221

Adalimumab Maintains Remission for Up to 4 Years in Patients WithUlcerative ColitisJean-Frederic Colombel, William Sandborn, Subrata Ghosh, Douglas C. Wolf, RemoPanaccione, Brian G. Feagan, Walter Reinisch, Anne Robinson, Andreas Lazar, MartinaKron, Bidan Huang, Roopal Thakkar

Background: Results from the clinical trials ULTRA 11 and ULTRA 2 2 demonstrated theefficacy of adalimumab (ADA) induction and maintenance therapy in the treatment ofulcerative colitis (UC) through week (wk) 52. The long-term efficacy and safety of ADAcontinues to be evaluated in the ongoing open-label (OL) extension, ULTRA 3. Methods:Patients (pts) who completed ULTRA 1 or 2 could enter ULTRA 3. Pts entering ULTRA 3from blinded therapy received ADA 40 mg every other week (eow) and those entering fromOL ADA, either eow or weekly (ew), continued on the same dosing regimen. Escalation toew dosing was allowed for flare or non-response during ULTRA 3. Partial Mayo score (PMS),Mayo score without endoscopy subscore, was calculated at every study visit. Endoscopieswere performed every 48 wks in ULTRA 3. Remission (PMS ≤ 2 with no subscore >1) andmucosal healing (MH) (endoscopy subscore ≤ 1) at year 4 after lead-in study baseline (BL)was assessed in the ITT pts who entered ULTRA 3 from ULTRA 1 and 2. Maintenance ofremission per PMS and maintenance of MH in year 4 was assessed in pts who enteredULTRA 3 in remission per full Mayo score (Mayo score ≤ 2 with no subscore >1) and withMH, respectively. Efficacy endpoints were measured, using a data cut-off of April 15, 2013,from ULTRA 3 entry (wk 0) through wk 156 (representing 208 wks from lead-in studyBL), for remission, and through wk 144 (representing 196 wks from lead-in study BL), forMH. Missing data were handled using last observation carried forward and non-responderimputation (NRI). Results: More than half of the pts from ULTRA 1 and 2 were followedin ULTRA 3 (588/1094, 53.7%). Of these pts, 52.2% (307/588, NRI) were in remission perPMS and 69.6% (409/588, NRI) had MH upon entry into ULTRA 3. At year 4 from lead-in study BL, remission per PMS and MH rates were 46.4% (273/588, NRI) and 50.7% (298/588, NRI), respectively. A majority of the pts entering ULTRA 3 with remission per fullMayo score or MH maintained remission per PMS and MH, respectively, over time (Table).Adverse event rates were stable over time and no new safety signals were observed. Conclu-sion: Long-term ADA therapy maintains remission and MH for up to four years in pts with

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sUC, with a stable safety profile and no new safety signals. References: 1. Reinisch, W, etal. Gut. 2011; 60:780. 2. Sandborn, WJ, et al. Gastroenterol. 2012; 142:257.Maintenance of remission per PMS and MH during ULTRA 3

N/A: not available due to the timing of endoscopies in ULTRA 3

Mo1222

Effects of Continued Vedolizumab Therapy for Ulcerative Colitis in Week 6Induction Therapy NonrespondersBrian G. Feagan, William Sandborn, Michael D. Smyth, Serap Sankoh, Asit Parikh, IrvingFox

Background: Vedolizumab (VDZ), a gut-selective, humanized, anti-α4β7 integrin monoclonalantibody, was evaluated for the treatment of ulcerative colitis (UC) in the 52-week GEMINI1 trial. In this study, 47.1% of patients had a clinical response to VDZ induction therapyat week 6. Here the efficacy of continuing VDZ therapy is evaluated in week 6 nonrespondersto VDZ induction therapy. Methods: GEMINI 1 participants were randomly assigned toreceive placebo (PBO) or VDZ 300 mg (cohort 1) or assigned to receive open-label VDZ(cohort 2) intravenously at weeks 0 and 2. Patients who did not respond to VDZ inductiontherapy at week 6 received open-label VDZ every 4 weeks (Q4W) during maintenance,whereas all PBO patients continued on PBO. Clinical response (reduction in partial MayoClinic score [MCS] of ≥2 points and decrease of ≥25% from the baseline score, with anaccompanying reduction in rectal bleeding subscore of ≥1 point or a rectal bleeding subscoreof 0 or 1) and clinical remission (partial MCS of ≤2 points and no subscore >1 point) wereassessed in week 6 nonresponders at weeks 10 and 14 (prespecified) and at week 52 (posthoc). Week 52 post hoc analyses were also performed for mucosal healing (Mayo Clinicscale endoscopic subscore of 0 or 1) in week 6 nonresponders and for efficacy end pointsin week 6 nonresponders who had clinical response at week 10 or 14. Results: At baseline,the median duration of UC in VDZ week 6 nonresponders (4.6 years) was comparable toweek 6 responders. Baseline UC activity (ie, complete MCS) was higher in VDZ week 6nonresponders (median, 9.0) than in week 6 responders (median, 8.0), which was attributablemainly to a greater proportion of patients with MCS of 9 to 12 (56% of week 6 nonresponders,42% of week 6 responders). Rate of previous tumor necrosis factor antagonist failure washigher among week 6 nonresponders (51%) than among week 6 responders (32%). Propor-tions of week 6 nonresponders who had clinical response, clinical remission, or mucosalhealing at weeks 10, 14, and 52 were numerically greater with VDZ than with PBO (Table).These differences were most pronounced at week 52. For both VDZ and PBO, the proportionsof week 6 nonresponders who had clinical response, clinical remission, or mucosal healingat week 52 were similar between those who responded at week 10 and those who respondedat week 14; the small numbers of PBO-treated patients in these subgroups are a limitationof this analysis. Conclusions: Patients with UC who did not have a clinical response to VDZinduction therapy at week 6 and continued VDZ Q4W had higher rates of clinical responseand remission at weeks 10, 14, and 52 and of mucosal healing at week 52 than did thosewho received PBO.

Mo1223

Health-Related Quality of Life in Patients With Ulcerative Colitis AfterTreatment With Vedolizumab: Results From the Gemini 1 StudyBrian G. Feagan, Jean-Frederic Colombel, David T. Rubin, Reema Mody, Serap Sankoh,Karen Lasch

Background: In the GEMINI 1 study, vedolizumab (VDZ)-treated patients with ulcerativecolitis (UC) had greater improvements in health-related quality of life (HRQoL), as assessedwith the Inflammatory Bowel Disease Questionnaire (IBDQ), than placebo (PBO)-treatedpatients. The analyses detailed here further describe VDZ effects on HRQoL using the 36-Item Short Form Health Survey (SF-36) and EQ-5D™ visual analogue scale (VAS) scoresand evaluate effects on IBDQ total and SF-36 summary scores by prior anti-tumor necrosisfactor (TNF) therapy status and baseline Mayo score. Methods: In the induction phase(weeks 0-6) of GEMINI 1, patients with UC received blinded VDZ 300 mg or PBO or open-label VDZ 300 mg at weeks 0 and 2. Patients who responded at week 6 were rerandomizedto receive VDZ 300 mg every 4 weeks (Q4W) or 8 weeks (Q8W) or PBO Q4W during themaintenance phase (weeks 6-52). Changes from baseline to weeks 6 and 52 in HRQoL endpoints were prospectively analyzed for the overall population. As post hoc analyses, changesin IBDQ total and SF-36 physical component summary (PCS) and mental componentsummary (MCS) scores also were analyzed by baseline disease activity (Mayo score <9 or≥9) and prior anti-TNF therapy (failure or naive). Proportions of patients with an IBDQtotal score ≥170 and those with clinically meaningful increases from baseline in IBDQ totalscore (≥16 points) and SF-36 MCS or PCS score (≥5 points) were also assessed. All analysesused the last-observation-carried-forward method. Results: Patients treated with VDZ hadgreater improvements from baseline to weeks 6 and 52 in SF-36 and EQ-5D VAS scoresthan PBO-treated patients (Table). IBDQ total and SF-36 PCS and MCS scores were alsoimproved with VDZ compared with PBO at weeks 6 and 52 for Mayo score <9 and anti-TNF-naive patient subgroups. For patients with Mayo score ≥9, VDZ improved IBDQ totaland SF-36 MCS scores at week 6 and IBDQ total and SF-36 PCS and MCS scores at week52 (Q8W only) compared with PBO. VDZ also improved IBDQ total and SF-36 PCS scoresversus PBO at week 6 in patients with prior anti-TNF failure. Proportions of patients withan IBDQ total score ≥170 were greater with VDZ at week 6 (37%) and week 52 (68%[Q4W]; 59% [Q8W]) than with PBO (week 6 [23%]; week 52 [38%]; P<0.005). Further,higher proportions of patients treated with VDZ than with PBO had clinically meaningfulincreases from baseline in IBDQ total and SF-36 PCS and MCS scores at week 6, and more

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of these patients had improvements with VDZ in IBDQ total (Q8W and Q4W) and SF-36PCS (Q8W) scores at week 52 compared with PBO. Conclusion: Patients with UC treatedwith VDZ had significant and clinically meaningful improvements in HRQoL, as measuredby both disease-specific and generic instruments, at weeks 6 and 52 compared with PBOacross disease severity and in difficult-to-treat UC.

Mo1224

Budesonide Foam for the Treatment of Patients With Mild-to-ModerateUlcerative Proctitis or Ulcerative Proctosigmoiditis: Subgroup Analyses of TwoRandomized, Placebo-Controlled, Phase 3 Clinical TrialsBrian Bosworth, William Sandborn, Salam F. Zakko, Glenn L. Gordon, David T. Rubin,Jing Yu, Andrew Barrett, Craig Paterson, William P. Forbes

Background: Treatment of distal ulcerative colitis (UC) is challenging. Oral therapies mayfail to distribute active drug to the distal colon, whereas rectal therapies (eg, enemas,suppositories) may be difficult for patients to retain. The objective of this analysis was tocharacterize the efficacy of an investigational rectal therapy, budesonide foam (BF), accordingto extent of distal disease—ulcerative proctitis (UP) and ulcerative proctosigmoiditis (UPS).Methods: Adults with endoscopically confirmed active mild-to-moderate UP (disease limitedto the rectum, extending 5 cm to ~15 cm from anal verge) or UPS (disease limited to therectum and sigmoid colon, extending to >15 cm to ~40 cm) with baseline Modified MayoDisease Activity Index (MMDAI) scores ≥5 and ≤10, with subscale ratings ≥2 for rectalbleeding and endoscopic appearance, were recruited into 2 identically designed, double-blind, randomized, phase 3 studies. Patients received BF 2 mg/25 mL or placebo (PBO)twice daily for 2 weeks, then once daily for 4 weeks. The primary endpoint was the percentageof patients achieving remission at week 6 (ie, endoscopy score ≤1 [no friability observed],rectal bleeding score of 0 [no blood observed], and improvement or no change from baselinein stool frequency MMDAI subscales). Key secondary endpoints included the percentage ofpatients achieving a rectal bleeding MMDAI subscale score = 0 and the percentage of patientsachieving an endoscopy MMDAI subscale score ≤1 at week 6. Results: The majority ofpatients in the pooled population had UPS (n = 390; 71.4%) compared with UP (n = 153;28.0%); the mean baseline total MMDAI score was 7.9. Pooled analyses at week 6 demon-strated that BF induced remission in more patients with UP and UPS relative to PBO (UP,30.6% vs 16.0%, P = 0.0315; UPS, 45.1% vs 26.9%, P = 0.0002; Table), resulting in treatmentgroup differences of 14.6% and 18.2%, respectively. A significantly greater percentage ofBF-treated patients with UPS (21.3% difference) and UP (16.3% difference) achieved a rectalbleeding MMDAI subscale score of 0 versus PBO (UPS, 52.8% vs 31.5%, P<0.0001; UP,36.1% vs 19.8%, P = 0.0242; Table). A significantly greater percentage of BF-treated patientswith UPS (19.9% difference) achieved an endoscopy MMDAI score ≤1 versus PBO (58.5%vs 38.6%, P = 0.0001; Table). Conclusions: Budesonide foam was significantly more effica-cious for the induction of UC remission in both subgroups (UP and UPS) of patientscompared with PBO. In addition, larger treatment differences versus PBO were noted in theUPS subgroup. These findings suggest that BF can improve symptoms in patients with distalUC. BF may satisfy an unmet medical need for targeted delivery of drug to the site of UCinflammation in the distal colon.Primary and Key Secondary Endpoints at 6 Weeks

UP = ulcerative proctitis; UPS = ulcerative proctosigmoiditis.