Volume 146, Issue 1, Pages 110-118.e3 (January 2014) Adalimumab Therapy Is Associated With Reduced Risk of Hospitalization in Patients With Ulcerative Colitis  Brian G. Feagan, William J. Sandborn, Andreas Lazar, Roopal B. Thakkar, Bidan Huang, Nattanan Reilly, Naijun Chen, Mei Yang, Martha Skup, Parvez Mulani, Jingdong Chao  Gastroenterology  Volume 146, Issue 1, Pages 110-118.e3 (January 2014) DOI: 10.1053/j.gastro.2013.09.032 Copyright © 2014 AGA Institute Terms and Conditions

Figure 1 ULTRA 1 and 2 study designs. (A) ULTRA 1 was an 8-week, double-blind, placebo-controlled induction trial of adalimumab in patients with moderately to severely active UC with an open-label extension for a total of 52 weeks. Under the original protocol, the adalimumab group received adalimumab (ADA) induction therapy of 160/80 mg at weeks 0/2 followed by ADA 40 mg eow starting at week 4. The placebo (PBO) group switched to adalimumab therapy (160/80-mg induction regimen at weeks 8/10) followed by 40 mg eow starting at week 12. (B) Under the amended protocol for ULTRA 1, a lower induction dose (80 mg at week 0, followed by 40 mg at week 2) was added. All patients received open-label ADA 40 mg eow starting at week 8. (C) ULTRA 2 was a 52-week, double-blind, placebo-controlled induction (160/80 mg) and maintenance (40 mg eow) trial of ADA in patients with moderately to severely active UC. Gastroenterology 2014 146, 110-118.e3DOI: (10.1053/j.gastro.2013.09.032) Copyright © 2014 AGA Institute Terms and Conditions

Figure 2 Incidence of hospitalization and colectomy in all patients during the first 8 weeks of therapy. Significant differences between the adalimumab and placebo groups were determined using the χ2 test. n, number of patients with event. Gastroenterology 2014 146, 110-118.e3DOI: (10.1053/j.gastro.2013.09.032) Copyright © 2014 AGA Institute Terms and Conditions

Figure 3 Event-based analysis of (A) all-cause, (B) UC-related, and (C) UC- or drug-related hospitalizations for all patients during the 52 weeks of therapy. Comparison between the adalimumab and placebo groups was performed by Poisson regression with time offset. n, number of hospitalizations; PY, patient-years. Gastroenterology 2014 146, 110-118.e3DOI: (10.1053/j.gastro.2013.09.032) Copyright © 2014 AGA Institute Terms and Conditions

Figure 4 Patient-based relative risk (RR) of hospitalization by study and for the combined studies. (A) The RR and corresponding 95% CI of all-cause hospitalization was determined for adalimumab (ADA) vs placebo (PBO) during the 52-week period of ULTRA 1 alone, ULTRA 2 alone, prior anti-TNF users, patients who were anti-TNF−naïve, and both trials combined. (B) The RR and corresponding 95% CI of UC-related hospitalization was determined for ADA vs PBO during the 52-week period of ULTRA 1 alone, ULTRA 2 alone, prior anti-TNF users, patients who were anti-TNF−naïve, and both trials combined. Gastroenterology 2014 146, 110-118.e3DOI: (10.1053/j.gastro.2013.09.032) Copyright © 2014 AGA Institute Terms and Conditions

Supplementary Figure 1 Accounting of hospitalization events of placebo subjects in the primary and sensitivity analyses. For the primary analysis, all events that occurred during the first 70 days after the switch from placebo (PBO) to adalimumab (ADA) therapy during the open-label (OL) period were included for the PBO group. For sensitivity approach 1, all events that occurred during the open-label period (ie, during ADA therapy) were excluded for the PBO group. For sensitivity approach 2, all events were attributed to the randomized groups regardless of whether patients treated with PBO had switched to OL therapy with ADA. DB; double-blind. Gastroenterology 2014 146, 110-118.e3DOI: (10.1053/j.gastro.2013.09.032) Copyright © 2014 AGA Institute Terms and Conditions

Supplementary Figure 2 Time-to-event Kaplan-Meier plots of (A) all-cause, (B) UC-related, and (C) UC- or drug-related hospitalizations for all patients during the 52 weeks of therapy. Comparison between the adalimumab and placebo groups was performed using log-rank tests. Gastroenterology 2014 146, 110-118.e3DOI: (10.1053/j.gastro.2013.09.032) Copyright © 2014 AGA Institute Terms and Conditions