Cimzia Versus Mesalamine for Crohn's Recurrence

NCT ID: NCT01696942

Last Updated: 2018-01-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2016-06-30

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.

Conditions

Crohn's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Cimzia

Intervention Type: DRUG

400 mg subcutaneously at weeks 4, 6, and 8 after surgery, and then every 4 weeks

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.

Group Type: ACTIVE_COMPARATOR

Mesalamine

Intervention Type: DRUG

mesalamine 800 mg orally three times daily

Interventions

Cimzia

400 mg subcutaneously at weeks 4, 6, and 8 after surgery, and then every 4 weeks

Intervention Type: DRUG

Mesalamine

mesalamine 800 mg orally three times daily

Intervention Type: DRUG

Other Intervention Names

Certolizumab

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UCB Pharma

INDUSTRY

Sponsor Role: collaborator

Milton S. Hershey Medical Center

OTHER

Sponsor Role: lead

Responsible Party

David B. Stewart, MD, FACS, FASCRS

Assistant Professor of Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David B Stewart, MD

Role: PRINCIPAL_INVESTIGATOR

Milton S. Hershey Medical Center

Locations

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Countries

United States

References

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. doi: 10.1016/0016-5085(85)90007-1.

Reference Type: BACKGROUND

PMID: 3996839 (View on PubMed)

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. No abstract available.

Reference Type: BACKGROUND

PMID: 467942 (View on PubMed)

Kyle J. Prognosis after ileal resection for Crohn's disease. Br J Surg. 1971 Oct;58(10):735-7. doi: 10.1002/bjs.1800581006. No abstract available.

Reference Type: BACKGROUND

PMID: 5097949 (View on PubMed)

Lennard-Jones JE, Stalder GA. Prognosis after resection of chronic regional ileitis. Gut. 1967 Aug;8(4):332-6. doi: 10.1136/gut.8.4.332. No abstract available.

Reference Type: BACKGROUND

PMID: 6039720 (View on PubMed)

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. doi: 10.1056/NEJM197510022931403.

Reference Type: BACKGROUND

PMID: 1160935 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19109962 (View on PubMed)

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. No abstract available.

Reference Type: BACKGROUND

PMID: 19485805 (View on PubMed)

Schreiber S. Certolizumab pegol for the treatment of Crohn's disease. Therap Adv Gastroenterol. 2011 Nov;4(6):375-89. doi: 10.1177/1756283X11413315.

Reference Type: BACKGROUND

PMID: 22043230 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21642014 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21223344 (View on PubMed)

Other Identifiers

36497

Identifier Type: -

Identifier Source: org_study_id