Crohn's Disease
Conditions
Keywords
Crohn's disease, certolizumab, mesalamine, recurrence
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.
Interventions
DRUGCimzia
400 mg subcutaneously at weeks 4, 6, and 8 after surgery, and then every 4 weeks
DRUGMesalamine
mesalamine 800 mg orally three times daily
Sponsors
UCB Pharma
Milton S. Hershey Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Cimzia: 400 mg subcutaneously at weeks 4, 6, and 8 after surgery, and then every 4 weeks | 3 |
| 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.
Mesalamine: mesalamine 800 mg orally three times daily | 2 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | screen failure | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Cimzia Treatment Arm | Mesalamine Treatment Arm | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 5 | 3 / 5 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 |
Outcome results
Primary
Clinical Recurrence Rates of Crohn's Disease
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
Population: Subjects who received CDAI questionnaire. Number of participants fluctuates due to withdrawals and missed appointments.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cimzia Treatment Arm | Clinical Recurrence Rates of Crohn's Disease | 3 month CDAI reccurence | 2 Participants |
| Cimzia Treatment Arm | Clinical Recurrence Rates of Crohn's Disease | 9 month CDAI recurrence | 2 Participants |
| Cimzia Treatment Arm | Clinical Recurrence Rates of Crohn's Disease | 6 month CDAI recurrence | 1 Participants |
| Cimzia Treatment Arm | Clinical Recurrence Rates of Crohn's Disease | 12 month CDAI recurrence | 0 Participants |
| Cimzia Treatment Arm | Clinical Recurrence Rates of Crohn's Disease | 4 week CDAI recurrence | 3 Participants |
| Mesalamine Treatment Arm | Clinical Recurrence Rates of Crohn's Disease | 12 month CDAI recurrence | 0 Participants |
| Mesalamine Treatment Arm | Clinical Recurrence Rates of Crohn's Disease | 4 week CDAI recurrence | 1 Participants |
| Mesalamine Treatment Arm | Clinical Recurrence Rates of Crohn's Disease | 3 month CDAI reccurence | 1 Participants |
| Mesalamine Treatment Arm | Clinical Recurrence Rates of Crohn's Disease | 6 month CDAI recurrence | 2 Participants |
| Mesalamine Treatment Arm | Clinical Recurrence Rates of Crohn's Disease | 9 month CDAI recurrence | 0 Participants |
Secondary
Number of Participants With Endoscopic Recurrence of Crohn's Disease
To compare the endoscopic recurrence rates at one year following surgery between patients treated with certolizumab and mesalamine.
Time frame: One year following enrollment
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cimzia Treatment Arm | Number of Participants With Endoscopic Recurrence of Crohn's Disease | 0 Participants |
| Mesalamine Treatment Arm | Number of Participants With Endoscopic Recurrence of Crohn's Disease | 0 Participants |