Cimzia Versus Mesalamine for Crohn's Recurrence

• Sponsor: Milton S. Hershey Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01696942
• Collaborator: UCB Pharma (Industry)
• Enrollment: 10
• Location: 1
• Arms: 2
• Duration (Months): 40
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Hypothesis: Cimzia provides superior reduction in endoscopic and clinical recurrence rates compared to mesalamine in the treatment of Crohn's disease one-year following ileocolectomy for Crohn's disease.

1. To evaluate the difference in clinical recurrence rates between certolizumab and mesalamine after 4 weeks, 3 months, 6 months, 9 months, and 12 months of use following ileocolectomy for Crohn's disease using the Crohn's Disease Activity Index (CDAI).

2. To compare the endoscopic recurrence rates at one year following surgery between patients treated with certolizumab and mesalamine.

3. To compare medication side-effects and tolerance of therapy, including the need to interrupt therapy due to side-effects, the incidence of opportunistic infections, and a general assessment of each patient's health and well-being using the short-form 36 (SF-36).

Condition or Disease	Intervention/Treatment	Phase
Crohn's Disease	Drug: Cimzia; Drug: Mesalamine	Phase 4

Detailed Description

Crohn's disease is an autoimmune, pan-intestinal disease which can affect any portion of the alimentary tract, but which has a preference for the small intestine, the colon, and the anus. It is now well established that Crohn's disease most commonly presents with an ileocolic distribution, followed by involvement of the small intestine, the colon, and the anus. Treatment for Crohn's disease is principally medical, reserving surgery to address complications from the disease which cannot be adequately resolved with medication alone. The single greatest challenge in treating this incurable disease is dealing with its recurrence rate. The cumulative probability of disease recurrence is quite high, with 75% of Crohn's patients requiring abdominal surgery at some point during their life.

Following surgery, recurrence rates are significant, varying depending on the manner in which recurrence is defined. With regard to clinical recurrences, where the recrudescence of the disease is associated with symptoms caused by new intestinal lesions, the recurrence rate is 10-20% per year.In some instances, clinical recurrences can appear within 3 months of surgery. Taking into account the need for additional surgery as defining a "surgical recurrence", reoperation rates for Crohn's disease range from 16% to 65% 10 years after a previous surgery. When recurrence is viewed from the vantage point of evidence of new Crohn's disease activity based on radiographic studies, radiographic recurrences range from 41-60% over the first 10 years following surgery. One of the most common measures of recurrence has become demonstrating evidence of new Crohn's disease activity based on colonoscopy. This endoscopic recurrence has consistently been shown to be as high as 50-75% at 3 months after surgery, and 50-90% at 12 months. It is widely accepted by physicians treating Crohn's patients that the appearance of endoscopic lesions has prognostic significance, as endoscopic evidence of Crohn's disease temporally precedes radiographic, clinical and surgical recurrences.

The role that Cimzia should play in preventing recurrence of Crohn's disease following ileocolectomy for Crohn's disease remains to be determined, as does its relative advantages and disadvantages compared to the use of mesalamine.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Use of Certolizumab Following Ileocolectomy Lowers Endoscopic and Histological Recurrence Rates for Crohn's Disease at One Year Compared to Mesalamine
• Study Start Date: Feb 1, 2013
• Actual Primary Completion Date: Jun 1, 2016
• Actual Study Completion Date: Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cimzia treatment arm Beginning at 4 weeks after surgery, patients would be randomly assigned using a pulled card method to receive certolizumab at a dose of 400 mg subcutaneously at weeks 4, 6, and 8 after surgery, and then every 4 weeks thereafter up to 12 months after enrollment.	Drug: Cimzia; 400 mg subcutaneously at weeks 4, 6, and 8 after surgery, and then every 4 weeks; Other Names: Certolizumab
Active Comparator: Mesalamine treatment arm Beginning at 4 weeks after surgery, patients would be randomly assigned to receive mesalamine 800 mg orally three times daily for twelve months following enrollment.	Drug: Mesalamine; mesalamine 800 mg orally three times daily

Outcome Measures

Primary Outcome Measures

1. Clinical Recurrence Rates of Crohn's Disease [4 weeks, 3 months, 6 months, 9 months, and 12 months]

   To evaluate the difference in clinical recurrence rates between certolizumab and mesalamine after 4 weeks, 3 months, 6 months, 9 months, and 12 months of use following ileocolectomy for Crohn's disease using the Crohn's Disease Activity Index (CDAI). CDAI scores of 150 or greater are considered a recurrence.

Secondary Outcome Measures

1. Number of Participants With Endoscopic Recurrence of Crohn's Disease [One year following enrollment]

   To compare the endoscopic recurrence rates at one year following surgery between patients treated with certolizumab and mesalamine.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients ≥18 years of age or older with Crohn's disease of any phenotype (luminal disease, perforating disease, stricturing disease) with an ileocolic distribution.

• Ileocolic Crohn's disease severe enough to require ileocolectomy (either open or laparoscopic).

Exclusion Criteria:

• Patients younger than 18 years of age, as there is little data on pediatric patients and since the Colorectal Surgery service only treats patients 18 years of age or older.

• Patients undergoing an ileocolectomy for any reason besides Crohn's disease.

• Patients requiring a stoma.

• Patients with short-bowel syndrome.

• Patients who are incarcerated, due to difficulties with frequent clinic visits given their incarceration and transportation issues.

• Patients who received previous anti-TNF therapy from infliximab or adalimumab within three months of surgery, or patients who have a history of a severe hypersensitivity reaction to infliximab or adalimumab

• Patients with a positive PPD and a suspicious finding on a chest x-ray suggestive of tuberculosis, or any patient with a history of tuberculosis.

• Patients who require postoperative therapy besides either mesalamine or certolizumab (steroids, antibiotics, and immunomodulator therapy would not be permitted starting at 4 weeks after ileocolectomy).

• Patients with significant psychiatric disorders (i.e. schizophrenia) and those with significant cognitive disorders, due to the difficulties with this patient group remaining compliant with frequent clinic visits, and due to the difficulty evaluating quality of life measures in these patients.

• Patients with a history of malignancy.

• Patients with a history of any demyelinating neurologic disease or a history of seizures.

• Patients with a history of severe congestive heart failure.

• Patients with a history of hepatitis B or C virus.

• Patients who are pregnant or who become pregnant.

• Involvement in any other clinical studies which use study medications.

• The subject has a condition, which, in the opinion of the investigator, would compromise the study or well-being of the subject or prevent the subject from meeting or performing the study requirements.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033

Sponsors and Collaborators

• Milton S. Hershey Medical Center
• UCB Pharma

Investigators

• Principal Investigator: David B Stewart, MD, Milton S. Hershey Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

• Cottone M, Mocciaro F, Orlando A. Infliximab prevents Crohn's disease recurrence after ileal resection. Expert Rev Gastroenterol Hepatol. 2009 Jun;3(3):231-4. doi: 10.1586/egh.09.13.
• Feagan BG, Sandborn WJ, Wolf DC, Coteur G, Purcaru O, Brabant Y, Rutgeerts PJ. Randomised clinical trial: improvement in health outcomes with certolizumab pegol in patients with active Crohn's disease with prior loss of response to infliximab. Aliment Pharmacol Ther. 2011 Mar;33(5):541-50. doi: 10.1111/j.1365-2036.2010.04568.x. Epub 2011 Jan 12.
• Greenstein AJ, Sachar DB, Pasternack BS, Janowitz HD. Reoperation and recurrence in Crohn's colitis and ileocolitis Crude and cumulative rates. N Engl J Med. 1975 Oct 2;293(14):685-90.
• Kyle J. Prognosis after ileal resection for Crohn's disease. Br J Surg. 1971 Oct;58(10):735-7.
• Lennard-Jones JE, Stalder GA. Prognosis after resection of chronic regional ileitis. Gut. 1967 Aug;8(4):332-6.
• Mekhjian HS, Switz DM, Watts HD, Deren JJ, Katon RM, Beman FM. National Cooperative Crohn's Disease Study: factors determining recurrence of Crohn's disease after surgery. Gastroenterology. 1979 Oct;77(4 Pt 2):907-13.
• Regueiro M, Schraut W, Baidoo L, Kip KE, Sepulveda AR, Pesci M, Harrison J, Plevy SE. Infliximab prevents Crohn's disease recurrence after ileal resection. Gastroenterology. 2009 Feb;136(2):441-50.e1; quiz 716. doi: 10.1053/j.gastro.2008.10.051. Epub 2008 Oct 31.
• Sandborn WJ, Schreiber S, Feagan BG, Rutgeerts P, Younes ZH, Bloomfield R, Coteur G, Guzman JP, D'Haens GR. Certolizumab pegol for active Crohn's disease: a placebo-controlled, randomized trial. Clin Gastroenterol Hepatol. 2011 Aug;9(8):670-678.e3. doi: 10.1016/j.cgh.2011.04.031. Epub 2011 May 13.
• Schreiber S. Certolizumab pegol for the treatment of Crohn's disease. Therap Adv Gastroenterol. 2011 Nov;4(6):375-89. doi: 10.1177/1756283X11413315.
• Whelan G, Farmer RG, Fazio VW, Goormastic M. Recurrence after surgery in Crohn's disease. Relationship to location of disease (clinical pattern) and surgical indication. Gastroenterology. 1985 Jun;88(6):1826-33.

• Responsible Party: David B. Stewart, MD, FACS, FASCRS, Assistant Professor of Surgery, Milton S. Hershey Medical Center
• ClinicalTrials.gov Identifier: NCT01696942
• Other Study ID Numbers: 36497
• First Posted: Oct 2, 2012
• Last Update Posted: Jan 12, 2018
• Last Verified: Dec 1, 2017

• Keywords provided by David B. Stewart, MD, FACS, FASCRS, Assistant Professor of Surgery, Milton S. Hershey Medical Center: Crohn's disease; certolizumab; mesalamine; recurrence
• Additional relevant MeSH terms: Crohn Disease; Recurrence; Mesalamine

Study Results

Participant Flow

Arm/Group Title	Cimzia Treatment Arm	Mesalamine Treatment Arm
Arm/Group Description	Beginning at 4 weeks after surgery, patients would be randomly assigned using a pulled card method to receive certolizumab at a dose of 400 mg subcutaneously at weeks 4, 6, and 8 after surgery, and then every 4 weeks thereafter up to 12 months after enrollment. Cimzia: 400 mg subcutaneously at weeks 4, 6, and 8 after surgery, and then every 4 weeks	Beginning at 4 weeks after surgery, patients would be randomly assigned to receive mesalamine 800 mg orally three times daily for twelve months following enrollment. Mesalamine: mesalamine 800 mg orally three times daily
Period Title: Overall Study
STARTED	5	5
COMPLETED	3	2
NOT COMPLETED	2	3

Baseline Characteristics

Arm/Group Title	Cimzia Treatment Arm	Mesalamine Treatment Arm	Total
Arm/Group Description	Beginning at 4 weeks after surgery, patients would be randomly assigned using a pulled card method to receive certolizumab at a dose of 400 mg subcutaneously at weeks 4, 6, and 8 after surgery, and then every 4 weeks thereafter up to 12 months after enrollment. Cimzia: 400 mg subcutaneously at weeks 4, 6, and 8 after surgery, and then every 4 weeks	Beginning at 4 weeks after surgery, patients would be randomly assigned to receive mesalamine 800 mg orally three times daily for twelve months following enrollment. Mesalamine: mesalamine 800 mg orally three times daily	Total of all reporting groups
Overall Participants	3	2	5
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 100%	2 100%	5 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	3 100%	2 100%	5 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 50%	1 20%
Not Hispanic or Latino	3 100%	1 50%	4 80%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	3 100%	2 100%	5 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Clinical Recurrence Rates of Crohn's Disease
Description	To evaluate the difference in clinical recurrence rates between certolizumab and mesalamine after 4 weeks, 3 months, 6 months, 9 months, and 12 months of use following ileocolectomy for Crohn's disease using the Crohn's Disease Activity Index (CDAI). CDAI scores of 150 or greater are considered a recurrence.
Time Frame	4 weeks, 3 months, 6 months, 9 months, and 12 months

Outcome Measure Data

Analysis Population Description

Subjects who received CDAI questionnaire. Number of participants fluctuates due to withdrawals and missed appointments.

Arm/Group Title	Cimzia Treatment Arm	Mesalamine Treatment Arm
Arm/Group Description	Beginning at 4 weeks after surgery, patients would be randomly assigned using a pulled card method to receive certolizumab at a dose of 400 mg subcutaneously at weeks 4, 6, and 8 after surgery, and then every 4 weeks thereafter up to 12 months after enrollment. Cimzia: 400 mg subcutaneously at weeks 4, 6, and 8 after surgery, and then every 4 weeks	Beginning at 4 weeks after surgery, patients would be randomly assigned to receive mesalamine 800 mg orally three times daily for twelve months following enrollment. Mesalamine: mesalamine 800 mg orally three times daily
Measure Participants	5	3
4 week CDAI recurrence	3 100%	1 50%
3 month CDAI reccurence	2 66.7%	1 50%
6 month CDAI recurrence	1 33.3%	2 100%
9 month CDAI recurrence	2 66.7%	0 0%
12 month CDAI recurrence	0 0%	0 0%

2. Secondary Outcome

Title	Number of Participants With Endoscopic Recurrence of Crohn's Disease
Description	To compare the endoscopic recurrence rates at one year following surgery between patients treated with certolizumab and mesalamine.
Time Frame	One year following enrollment

Outcome Measure Data

Analysis Population Description

Subjects available for colonoscopy at 12 month visit. This visit was sometimes separated from the overall 12-month visit so only 1 (cimzia) and 2 (mesalamine) patients respectively had the colonoscopy performed.

Arm/Group Title	Cimzia Treatment Arm	Mesalamine Treatment Arm
Arm/Group Description	Beginning at 4 weeks after surgery, patients would be randomly assigned using a pulled card method to receive certolizumab at a dose of 400 mg subcutaneously at weeks 4, 6, and 8 after surgery, and then every 4 weeks thereafter up to 12 months after enrollment. Cimzia: 400 mg subcutaneously at weeks 4, 6, and 8 after surgery, and then every 4 weeks	Beginning at 4 weeks after surgery, patients would be randomly assigned to receive mesalamine 800 mg orally three times daily for twelve months following enrollment. Mesalamine: mesalamine 800 mg orally three times daily
Measure Participants	1	2
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Arm/Group Title	Cimzia Treatment Arm		Mesalamine Treatment Arm
Arm/Group Description	Beginning at 4 weeks after surgery, patients would be randomly assigned using a pulled card method to receive certolizumab at a dose of 400 mg subcutaneously at weeks 4, 6, and 8 after surgery, and then every 4 weeks thereafter up to 12 months after enrollment. Cimzia: 400 mg subcutaneously at weeks 4, 6, and 8 after surgery, and then every 4 weeks		Beginning at 4 weeks after surgery, patients would be randomly assigned to receive mesalamine 800 mg orally three times daily for twelve months following enrollment. Mesalamine: mesalamine 800 mg orally three times daily
All Cause Mortality
	Cimzia Treatment Arm		Mesalamine Treatment Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cimzia Treatment Arm		Mesalamine Treatment Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Cimzia Treatment Arm		Mesalamine Treatment Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		3/5 (60%)
Blood and lymphatic system disorders
anemia	1/5 (20%)	1	0/5 (0%)	0
Eye disorders
Episcleritis	1/5 (20%)	1	0/5 (0%)	0
Gastrointestinal disorders
Diarrhea	2/5 (40%)	2	1/5 (20%)	1
nausea	2/5 (40%)	2	0/5 (0%)	0
ulcer (anastamotic)	1/5 (20%)	1	0/5 (0%)	0
melena	1/5 (20%)	1	0/5 (0%)	0
constipation	1/5 (20%)	1	0/5 (0%)	0
fecal calprotectin elevation	1/5 (20%)	1	0/5 (0%)	0
colon inflammation	1/5 (20%)	1	0/5 (0%)	0
cramping with BM	1/5 (20%)	1	0/5 (0%)	0
Crohn's flare	1/5 (20%)	1	0/5 (0%)	0
General disorders
dehydration	1/5 (20%)	1	1/5 (20%)	1
fatigue	2/5 (40%)	2	1/5 (20%)	1
Abdominal Pain	2/5 (40%)	2	0/5 (0%)	0
insomnia	0/5 (0%)	0	1/5 (20%)	1
Headache	1/5 (20%)	1	1/5 (20%)	1
Elevated CRP	1/5 (20%)	1	0/5 (0%)	0
Infections and infestations
Urinary Tract infection	0/5 (0%)	0	1/5 (20%)	2
Musculoskeletal and connective tissue disorders
Musculoskeletal ache	2/5 (40%)	2	0/5 (0%)	0
Nervous system disorders
seizure	0/5 (0%)	0	1/5 (20%)	1
Psychiatric disorders
Attention Deficit	1/5 (20%)	1	0/5 (0%)	0
panic attack	0/5 (0%)	0	1/5 (20%)	1
Respiratory, thoracic and mediastinal disorders
upper respiratory infection	1/5 (20%)	1	0/5 (0%)	0
pulmonary nodules	0/5 (0%)	0	1/5 (20%)	1
Skin and subcutaneous tissue disorders
Perianal rash	1/5 (20%)	1	1/5 (20%)	1
papular rash	2/5 (40%)	2	0/5 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.