Association Between Plasma Concentrations of Certolizumab Pegol and Endoscopic Outcomes of Patients With Crohn's Disease  Jean–Frédéric Colombel, William J. Sandborn, Matthieu Allez, Jean–Louis Dupas, Olivier Dewit, Geert D'Haens, Yoram Bouhnik, Gerald Parker, Bosny Pierre–Louis, Xavier Hébuterne  Clinical Gastroenterology and Hepatology  Volume 12, Issue 3, Pages 423-431.e1 (March 2014) DOI: 10.1016/j.cgh.2013.10.025 Copyright © 2014 AGA Institute Terms and Conditions

Figure 1 Study design. After a screening period of 1 week, patients entered the 52-week treatment period and a 2-week follow-up period. CZP 400 mg was administered subcutaneously at weeks 0, 2, and 4 (loading dose), and then every 4 weeks (q4w) until week 52. If a patient did not achieve clinical response or clinical remission by week 10, or if clinical response was lost (clinician judgment) after week 10, the dose of CZP was escalated to 400 mg every 2 weeks (q2w). CZP plasma concentrations were collected at weeks 8 and 54 and stratified by quartiles. Rates of endoscopic response (CDEIS decrease from baseline, >5) and remission (CDEIS, <6) were determined at weeks 10 and 54. Loss of clinical response was defined as CDAI greater than 150 and an increase in CDAI of 70 points or more at 2 consecutive visits vs week 10. Clinical Gastroenterology and Hepatology 2014 12, 423-431.e1DOI: (10.1016/j.cgh.2013.10.025) Copyright © 2014 AGA Institute Terms and Conditions

Figure 2 Associations between clinical and endoscopic responses or remission at week 10 and plasma CZP concentrations at week 8. Receiver operating curves from logistic regression model. (A) For endoscopic response the area under the curve is 0.7593. (B) For endoscopic remission the area under the curve is 0.6940. (C) For clinical response the area under the curve is 0.5576 and (D) for clinical remission the area under the curve is 0.7045. Clinical Gastroenterology and Hepatology 2014 12, 423-431.e1DOI: (10.1016/j.cgh.2013.10.025) Copyright © 2014 AGA Institute Terms and Conditions

Figure 3 Rates of endoscopic response and remission and clinical response and remission at week 10 by CZP plasma concentration quartiles (μg/mL) at week 8 (trough). Patients received a loading dose of CZP 400 mg at weeks 0, 2, and 4, followed by CZP 400 mg every 4 weeks. Error bars represent 95% CIs. P values indicate the comparison of outcomes across quartiles. (A) Patients with endoscopic response and remission at week 10. (B) Patients with clinical response and remission at week 10. Clinical Gastroenterology and Hepatology 2014 12, 423-431.e1DOI: (10.1016/j.cgh.2013.10.025) Copyright © 2014 AGA Institute Terms and Conditions

Supplementary Figure 1 Rates of endoscopic response and remission and clinical response and remission at week 54 by CZP plasma concentration quartiles (μg/mL) at week 54 (2-week midpoint). Patients received CZP 400 mg at weeks 0, 2, and 4 (loading dose), followed by CZP 400 mg every 4 weeks to week 54. Error bars represent 95% CIs. P values indicate comparison of outcomes across quartiles. (A) Patients with endoscopic response and remission at week 54. (B) Patients with clinical response and remission at week 54. Clinical Gastroenterology and Hepatology 2014 12, 423-431.e1DOI: (10.1016/j.cgh.2013.10.025) Copyright © 2014 AGA Institute Terms and Conditions