Volume 126, Issue 2, Pages 402-413 (February 2004) Comparison of scheduled and episodic treatment strategies of infliximab in Crohn’s disease  Paul Rutgeerts, Brian G. Feagan, Gary R. Lichtenstein, Lloyd F. Mayer, Stefan Schreiber, Jean Frederic Colombel, Daniel Rachmilewitz, Douglas C. Wolf, Allan Olson, Weihang Bao, Stephen B. Hanauer  Gastroenterology  Volume 126, Issue 2, Pages 402-413 (February 2004) DOI: 10.1053/j.gastro.2003.11.014

Figure 1 (A ) Summary of patient disposition through week 54 of maintenance treatment. Five hundred eighty patients received an initial infusion of infliximab at week 0. Seven patients discontinued from the study prior to randomization. At week 2, 573 patients were stratified by response status and randomized to 1 of 3 treatment strategy groups. The numbers in the boxes represent patients who continued through each visit. The numbers of patients who withdrew are shown at each visit by the arrows to the left (with totals at each visit) and are totaled in the octagon at the bottom of the Figure. At week 14 or later, patients who had responded to infliximab therapy at any time during the trial but then worsened were eligible to cross over to active episodic treatment with infliximab 5, 10, and 15 mg/kg for patients originally assigned to the episodic treatment, 5 mg/kg scheduled treatment, and 10 mg/kg scheduled treatment strategy groups, respectively. Worsening was defined by (1) an increase in the CDAI of at least 70 points from the baseline score with a total score of at least 175 and an increase in the CDAI of 35% or more from the baseline value or (2) the introduction of a new treatment or an increase in the dose of an existing treatment for active Crohn’s disease. The numbers of patients crossing over to episodic treatment are indicated by arrows to the right and are totaled in the circles. (B) Summary of disposition for patients who crossed over to episodic treatment. At week 14 or later, patients who had responded to infliximab therapy at any time during the trial but then worsened were eligible to cross over to active episodic treatment with infliximab 5, 10, and 15 mg/kg for patients originally assigned to the episodic treatment, 5 mg/kg scheduled treatment, and 10 mg/kg scheduled treatment strategy groups, respectively. Worsening was defined by (1) an increase in the CDAI of at least 70 points from the baseline score with a total score of at least 175 and an increase in the CDAI of 35% or more from the baseline value or (2) the introduction of a new treatment or an increase in the dose of an existing treatment for active Crohn’s disease. The numbers of patients who crossed over to episodic treatment at each visit are indicated by arrows entering the box from the right. The numbers of patients followed in the episodic treatment phase at each visit are indicated by the numbers within the boxes. The numbers of patients withdrawing from episodic treatment are shown by visit (with totals at each visit) and are totaled in the octagons at the bottom of the Figure. Gastroenterology 2004 126, 402-413DOI: (10.1053/j.gastro.2003.11.014)

Figure 1 (A ) Summary of patient disposition through week 54 of maintenance treatment. Five hundred eighty patients received an initial infusion of infliximab at week 0. Seven patients discontinued from the study prior to randomization. At week 2, 573 patients were stratified by response status and randomized to 1 of 3 treatment strategy groups. The numbers in the boxes represent patients who continued through each visit. The numbers of patients who withdrew are shown at each visit by the arrows to the left (with totals at each visit) and are totaled in the octagon at the bottom of the Figure. At week 14 or later, patients who had responded to infliximab therapy at any time during the trial but then worsened were eligible to cross over to active episodic treatment with infliximab 5, 10, and 15 mg/kg for patients originally assigned to the episodic treatment, 5 mg/kg scheduled treatment, and 10 mg/kg scheduled treatment strategy groups, respectively. Worsening was defined by (1) an increase in the CDAI of at least 70 points from the baseline score with a total score of at least 175 and an increase in the CDAI of 35% or more from the baseline value or (2) the introduction of a new treatment or an increase in the dose of an existing treatment for active Crohn’s disease. The numbers of patients crossing over to episodic treatment are indicated by arrows to the right and are totaled in the circles. (B) Summary of disposition for patients who crossed over to episodic treatment. At week 14 or later, patients who had responded to infliximab therapy at any time during the trial but then worsened were eligible to cross over to active episodic treatment with infliximab 5, 10, and 15 mg/kg for patients originally assigned to the episodic treatment, 5 mg/kg scheduled treatment, and 10 mg/kg scheduled treatment strategy groups, respectively. Worsening was defined by (1) an increase in the CDAI of at least 70 points from the baseline score with a total score of at least 175 and an increase in the CDAI of 35% or more from the baseline value or (2) the introduction of a new treatment or an increase in the dose of an existing treatment for active Crohn’s disease. The numbers of patients who crossed over to episodic treatment at each visit are indicated by arrows entering the box from the right. The numbers of patients followed in the episodic treatment phase at each visit are indicated by the numbers within the boxes. The numbers of patients withdrawing from episodic treatment are shown by visit (with totals at each visit) and are totaled in the octagons at the bottom of the Figure. Gastroenterology 2004 126, 402-413DOI: (10.1053/j.gastro.2003.11.014)

Figure 2 Proportion of patients with different extent of exposure to infliximab by treatment group. Gastroenterology 2004 126, 402-413DOI: (10.1053/j.gastro.2003.11.014)

Figure 3 Median CDAI scores at each visit through week 54. Clinical remission is defined as a CDAI score <150. The numbers of patients evaluated were as follows: episodic, n = 188; 5 mg/kg scheduled, n = 192; 10 mg/kg scheduled, n = 193. Only significant P values are presented. Gastroenterology 2004 126, 402-413DOI: (10.1053/j.gastro.2003.11.014)

Figure 4 (A) Proportion of patients in clinical remission through week 54. Clinical remission was defined as a CDAI <150 points. The numbers of patients evaluated were as follows: episodic, n = 188; 5 mg/kg scheduled, n = 192; 10 mg/kg scheduled, n = 193. Only significant P values are presented. (B) Proportion of patients in clinical response through week 54. Clinical response was defined as reduction in CDAI ≥70 points and ≥25% from baseline. The numbers of patients evaluated were as follows: episodic, n = 188; 5 mg/kg scheduled, n = 192; 10 mg/kg scheduled, n = 193. Only significant P values are presented. Gastroenterology 2004 126, 402-413DOI: (10.1053/j.gastro.2003.11.014)

Figure 5 Proportion of patients with IBDQ score >170 at each visit through week 54. IBDQ scores >170 generally indicate remission of disease. The numbers of patients evaluated were 188 patients in the episodic strategy, 192 patients in the 5 mg/kg scheduled strategy, and 193 patients in the 10 mg/kg scheduled strategy. Only significant P values are presented. Gastroenterology 2004 126, 402-413DOI: (10.1053/j.gastro.2003.11.014)

Figure 6 Proportion of patients demonstrating mucosal healing at week 54. Ninety-nine patients were enrolled and randomized in the endoscopic substudy at selected North American and European sites. Mucosal ulceration was present in 82% (81/99) of patients at baseline. Seventy-four and 58 patients had follow-up endoscopy at weeks 10 and 54, respectively. Mucosal healing was defined as the complete absence of mucosal ulcerations that were observed at baseline. Gastroenterology 2004 126, 402-413DOI: (10.1053/j.gastro.2003.11.014)

Figure 7 Number of Crohn’s disease-related hospitalizations per 100 patients. Gastroenterology 2004 126, 402-413DOI: (10.1053/j.gastro.2003.11.014)

Figure 8 Proportion of patients with Crohn’s disease-related intra-abdominal surgeries. Gastroenterology 2004 126, 402-413DOI: (10.1053/j.gastro.2003.11.014)