Cimzia Versus Mesalamine for Crohn's Recurrence

Phase 4

Terminated

• Conditions: Crohn's Disease
• Interventions: Drug: Cimzia; Drug: Mesalamine

• Registration Number: NCT01696942
• Lead Sponsor: Milton S. Hershey Medical Center

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).

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 Timeline

• Study First Submitted: 2012-09-25
• Study First Submitted QC: 2012-10-01
• Study First Posted: 2012-10-02
• Study Start: 2013-02
• Primary Completion: 2016-06
• Study Completion: 2016-06
• Results First Submitted: 2017-09-13
• Results First Submitted QC: 2017-09-13
• Results First Posted: 2017-10-10
• Status Verified: 2017-12
• Last Update Submitted: 2017-12-13
• Last Update Posted: 2018-01-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 10

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).

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cimzia treatment arm	Cimzia	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.
Mesalamine treatment arm	Mesalamine	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.

Trial Locations

Locations (1)

Penn State Milton S. Hershey Medical Center; 🇺🇸 Hershey, Pennsylvania, United States