Slides compiled by Dr. Najma Ahmed A treat to target approach decreases the rate of CD-related adverse outcomes versus a clinical approach in patients with moderate to severely active Crohn’s disease: Data from CALM Colombel J, Panaccione R, Bossuyt P, et al. Slides compiled by Dr. Najma Ahmed UEGW 2017

Introduction Background and objectives Methods Primary results of CALM showed a treat-to-target (T2T) approach led to superior endoscopic and deep remission vs standard clinical management (CM) in CD1,2 Objective: To assess adverse outcomes (e.g., hospitalizations) in CALM Methods N=244 (122 in CM, 122 in T2T), baseline characteristics similar between groups Mean age ± SD, 31.6 ± 11.7 years; mean CD duration ± SD, 0.95 ± 1.98 years Treatment at randomization and at Weeks 11, 23 and 35 based on failure to fulfil success criteria: CDAI < 150, CRP < 5 mg/L, FC < 250 mg/g, no prednisone use T2T: Escalation driven by CDAI, FC, CRP, prednisone use CM: Escalation driven by CDAI, prednisone use Further details about methodology are available in the DDW 2017 CALM summary2 CD: Crohn’s disease; CDAI: Crohn’s Disease Activity Index; CRP: C-reactive protein; FC: fecal calprotectin; SD: standard deviation 1. Colombel JF, et al. Lancet 2017; DOI: 10.1016/S0140-6736(17)32641-7. 2. IBD Update. Treat to target vs clinical management in CD: CALM. DDW 2017. Summary slides available here.

Method Endpoints evaluated at 48 weeks after randomization Endpoint Description CD-related hospitalization* On or after randomization and ≤ 70 days after last dose CD-related surgical procedure Major: Bowel resection, ostomy, by-pass, strictureplasty, surgical drainage of abdominal/pelvic abscess Non-major: Debridement, abscess drainage, seton placement, fistulotomy, TPN access line CD-related hospitalization* OR serious complication CD-related hospitalization OR Abscess, fistula or stricture, skin or ocular EIM, or serious adverse drug reaction (from randomization up to Week 48 or last dose) Time to CD-related flare Time to increase in CDAI ≥ 70 points from 1 week prior to randomization OR early randomization CDAI and CDAI > 220 *Other than for CD-related major surgery CDAI: Crohn’s Disease Activity Index; EIM: extra-intestinal manifestation; TPN: total parenteral nutrition

Rates of CD-related hospitalizations after randomization Results Compared with clinical management, treat to target was associated with significant reductions in: CD-related hospitalizations Time to CD-related flare (next slide) No significant difference: CD-related surgical procedure CD-related hospitalizations or serious complications Rates of CD-related hospitalizations after randomization P = 0.021 Events/100 PY 29 events 14 events Treat to Target N = 122 PY = 103.6 N = 122 PY = 106.3 CD: Crohn’s Disease *CD-related hospitalization, other than CD-related major surgery, on or after randomization and ≤ 70 days after last dose.

Results Time to CD-related flare* There was an early separation in the time to CD-related flare between the clinical management and T2T groups Log-rank P=0.010 HR=0.4 95% CI 0.2-0.8, P=0.012 Proportion of patients without CD flare Clinical Management T2T Week after randomization No. at risk 122 97 94 85 78 75 107 105 101 86 CD: Crohn’s Disease; T2T: treat to target *CD-related flare: Increase in CDAI ≥ 70 points from 1 week prior to randomization OR early randomization CDAI and CDAI > 200

Conclusions & significance to clinical practice A treat-to-target approach led to reduced CD-related hospitalizations and time to CD-related flare compared with standard clinical management Significance to clinical practice Need to correlate clinical symptoms with objective data prior to making treatment decisions Study limitations include short-term data (1 year), new-onset disease (within 1 year) and IMM- and biologic-naive CD: Crohn’s disease; IMM: immunomodulator