Familial Adenomatous Polyposis (FAP)
Conditions
Keywords
Familial adenomatous polyposis, celecoxib, IRA, IPAA
Brief summary
This is a registry-based observational study assessing clinical outcomes in FAP patients receiving celecoxib compared with historical/concurrent registry patients who have not received celecoxib. Both retrospective and prospective data will be utilized. No sampling methods apply.
Detailed description
The study prematurely discontinued on April 11, 2008 due to slow enrollment. It should be noted that safety concerns have not been seen in this study and have not factored into this decision.
Interventions
DRUGCelecoxib
800 mg total daily dosing
OTHERRoutine Medical Care
Sponsors
Pfizer
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Celecoxib Treated Patients: * Diagnosis of FAP based on the expression of the FAP phenotype. * Celecoxib treatment prescribed outside of a clinical trial setting with expected duration of celecoxib treatment of at least six months. Historical/Concurrent Control Patients: * Diagnosis of FAP based on the expression of the FAP phenotype. * Be greater than or equal to 12 years old at the time of study enrollment. * Have an endoscopically assessable colonic, rectal, ileal pouch and/or gastroduodenal segment. * For the group of post-surgical patients, IRA or IPAA performed from 1985 onward (in order to assure standardized surgical techniques and post-surgical management). Patients whose primary colorectal surgery was performed prior to 1985 will not be eligible to serve as historical controls.
Exclusion criteria
Celecoxib Treated Patients: * Have received a pharmacological treatment (other than celecoxib) within the last 3 months for their FAP disease including treatment of any extracolonic manifestation of FAP. * Have received a non-steroidal anti-inflammatory drug (NSAID) within the last 3 months, other than celecoxib, for any reason. Historical/Concurrent Control Patients: * Have pharmacological treatment recorded for their FAP disease at the defined index date. * Have received a non-steroidal anti-inflammatory drug (NSAID) within the last 3 months for any reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time From Ileorectal Anastomosis (IRA) to Time of First Excisional Polypectomy of a Rectal Polyp Post IRA | Up to 8 years prior to baseline | Time(months): \[date of first excisional polypectomy of rectal polyp post IRA minus date of prior IRA plus 1\] divided by 30.44. Baseline = start of study follow-up: start of on-study celecoxib treatment period for celecoxib-treated subjects and comparable to index date for control subjects. Index date calculated as Matched Celecoxib-treated patients: number of days from most recent FAP-related surgery (IRA or IPAA) to start of study follow-up; add this number of days to matched control patient's most recent FAP-related surgery date=index date for Matched Control. |
| Time From Start of Study Follow-up to the Time of First Excisional Polypectomy of a Rectal Polyp Post IRA | Baseline, Up to 60 months post-baseline | Time(months): \[date of first excisional polypectomy of rectal polyp post IRA minus date of start of study follow-up plus 1\] divided by 30.44. |
| Time From Ileopouch Anal Anastomosis (IPAA) to Time of First Excisional Polypectomy of a Rectal Polyp Post IPAA | Up to 15 years prior to baseline | Time (months): \[date of first excisional polypectomy of a rectal polyp post IPAA minus date of prior IPAA plus 1\] divided by 30.44. Baseline = start of study follow-up: start of on-study celecoxib treatment period for celecoxib-treated subjects and comparable to index date for control subjects. Index date calculated as Matched Celecoxib-treated patients: number of days from most recent FAP-related surgery (IRA or IPAA) to start of study follow-up; add this number of days to matched control patient's most recent FAP-related surgery date=index date for Matched Control. |
| Time From Start of Study Follow-up to Time of First Excisional Polypectomy of a Rectal Polyp Post IPAA | Baseline, Up to 60 months post-baseline | Time (months): \[date of first excisional polypectomy of rectal polyp post IPAA minus date of start of study follow-up plus 1\] divided by 30.44. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time From Post IRA to Time of Conversion From IRA to IPAA | Up to 15 years prior to baseline | Time (months): \[date of IPAA minus date of prior IRA plus 1\] divided by 30.44. |
| Time From Start of Study Follow-up to Time of Conversion From IRA to IPAA | Baseline, Up to 60 months post-baseline | Time (months): \[date of IPAA minus date of start of study follow-up plus 1\] divided by 30.44. |
| Time From Most Recent Prior FAP-related Surgical Event or Onset of FAP Phenotype to Time of First Excisional or Ablational Event for Rectal, Colonic, Pouch, or Duodenal Adenomas (Duodenal Adenomatous Polyps) | Up to 15 years prior to baseline | Time (months): \[date of first excisional or ablational event for colonic, pouch, or duodenal adenomas occuring after date of most recent prior FAP-related surgical event or date of FAP diagnosis minus date of most recent prior FAP-related surgical event or date of FAP diagnosis plus 1\] divided by 30.44. |
| Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline, 6 to 14 months post-baseline, EOS | Number of subjects with polyp burden as assessed in most recent prior polyps evaluation: attenuated: \<100 polyps, mild: between 100 to 1000 polyps, severe: \>1000 polyps. EOS: endoscopic examination closest to end of on-study celecoxib or index period (within 6 months of end of celecoxib or index period and prior to intake of any exclusionary medications after baseline). |
| Duodenal Adenoma Burden as Measured by Spigelman Stage | Baseline, 6 to 14 months post-baseline, End of study (EOS) | Number of subjects with polyp burden as assessed in most recent prior polyps evaluation: Spigelman stage provides index of disease severity based on number of polyps, polyp size, histology, and dysplasia; range is Stage 0 (none) to Stage IV (severe). EOS: endoscopic examination closest to end of on-study celecoxib or index period (within 6 months of end of celecoxib or index period and prior to intake of any exclusionary medications after baseline). Spigelman Stage not completed as staging data largely missing; see measure: Duodenal adenoma burden as measured by polyp counts. |
| Time From Start of Study Follow-up to Time of First Excisional or Ablational Event for Rectal, Colonic, Pouch, or Duodenal Adenomas | Baseline, Up to 60 months post-baseline | Time (months): \[date of first excisional or ablational event for colonic, pouch, or duodenal adenomas, occurring after date of most recent prior FAP-related surgical event, or date of FAP diagnosis minus date of start of study follow-up plus 1\] divided by 30.44. |
| Time From Most Recent Prior FAP-related Surgical Event or Onset of FAP Phenotype to Time of First FAP-related Adverse Event | Up to 15 years prior to baseline | Time (months): \[date of first FAP-related adverse event, occurring after the date of most recent prior FAP-related surgery, or date of FAP diagnosis minus date of most recent prior FAP-related surgery, or date of FAP diagnosis plus 1\] divided by 30.44. FAP-related adverse event defined as any FAP related cancers, desmoid tumors requiring procedural intervention, hospitalizations or procedural interventions, or death related to FAP (i.e., as a consequence of FAP, FAP complications, or a procedure or drug used to treat FAP-related medical problems). |
| Time From Start of Study Follow-up to Time of First FAP-related Adverse Event | Baseline, Up to 60 months post-baseline | Time (months): \[date of first FAP-related adverse event, occurring after the date of the most recent prior FAP-related surgery, or date of FAP diagnosis minus date of start of study follow-up plus 1\] divided by 30.44. FAP-related adverse event defined as any FAP related cancers, desmoid tumors requiring procedural intervention, hospitalizations or procedural interventions, or death related to FAP (i.e., as a consequence of FAP, FAP complications, or a procedure or drug used to treat FAP-related medical problems). |
Countries
Canada, Denmark, Spain, United States
Participant flow
Recruitment details
Study prematurely discontinued in May 2008 prior to reaching planned enrollment target; Last subject last visit November 2008.
Pre-assignment details
Familial Adenomatous Polyposis (FAP) identified subjects=celecoxib-treated and matched control subjects eligible for inclusion in study identified from 4 registry sites; FAP analyzed=celecoxib-treated and matched control subjects eligible for matching and analysis in study. 1 subject excluded from analysis; took celecoxib without a prescription.
Participants by arm
| Arm | Count |
|---|---|
| Matched Celecoxib Treated Celecoxib treatment prescribed outside clinical trial setting per routine medical care; matched to control subjects. Routine medical care: celecoxib is prescribed in the usual manner in accordance with the terms of the marketing authorization and as prescribed in medical practice. The assignment of the patient to celecoxib is not decided in advance by the study protocol but falls within current practice. All patients regardless of treatment status are followed according to local standard of medical care by the respective physicians. | 13 |
| Matched Control Observation of subjects not treated with celecoxib and followed according to routine medical practice; matched to matched celecoxib treated subjects. Routine medical practice: all patients regardless of treatment status are followed according to local standard of medical care by the respective physicians. | 13 |
| Not Matched Celecoxib Treated Celecoxib treatment prescribed outside clinical trial setting per routine medical care; not matched to control subjects. Routine medical care: celecoxib is prescribed in the usual manner in accordance with the terms of the marketing authorization and as prescribed in medical practice. The assignment of the patient to celecoxib is not decided in advance by the study protocol but falls within current practice. All patients regardless of treatment status are followed according to local standard of medical care by the respective physicians. | 41 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| FAP Analyzed Subjects | Lost to Follow-up | 0 | 2 |
| FAP Analyzed Subjects | Other study participation | 0 | 1 |
| FAP Identified Subjects | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Matched Celecoxib Treated | Matched Control | Not Matched Celecoxib Treated |
|---|---|---|---|---|
| Age, Customized 25 to 34 years | 14 participants | 5 participants | 4 participants | 5 participants |
| Age, Customized <25 years | 27 participants | 4 participants | 5 participants | 18 participants |
| Age, Customized 35 to 44 years | 13 participants | 3 participants | 2 participants | 8 participants |
| Age, Customized 45 to 54 years | 5 participants | 1 participants 11.24 | 1 participants 9 | 3 participants |
| Age, Customized 55 to 64 years | 1 participants | 0 participants | 0 participants | 1 participants |
| Age, Customized >64 years | 0 participants | 0 participants | 0 participants | 0 participants |
| Age, Customized Age not available (no surgery) | 7 participants | 0 participants | 1 participants | 6 participants |
| Sex: Female, Male Female | 29 Participants | 2 Participants | 6 Participants | 21 Participants |
| Sex: Female, Male Male | 38 Participants | 11 Participants | 7 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 54 |
| serious Total, serious adverse events | 5 / 54 |
Outcome results
Primary
Time From Ileopouch Anal Anastomosis (IPAA) to Time of First Excisional Polypectomy of a Rectal Polyp Post IPAA
Time (months): \[date of first excisional polypectomy of a rectal polyp post IPAA minus date of prior IPAA plus 1\] divided by 30.44. Baseline = start of study follow-up: start of on-study celecoxib treatment period for celecoxib-treated subjects and comparable to index date for control subjects. Index date calculated as Matched Celecoxib-treated patients: number of days from most recent FAP-related surgery (IRA or IPAA) to start of study follow-up; add this number of days to matched control patient's most recent FAP-related surgery date=index date for Matched Control.
Time frame: Up to 15 years prior to baseline
Population: All eligible subjects with IPAA performed prior to start of study follow-up included and with first excisional polypectomy of a rectal polyp post IPAA. No control group subjects (n=7) had a post-IPAA polypectomy (no data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Matched Celecoxib Treated | Time From Ileopouch Anal Anastomosis (IPAA) to Time of First Excisional Polypectomy of a Rectal Polyp Post IPAA | 152.7 months | Standard Deviation 42.1 |
| All Celecoxib Treated | Time From Ileopouch Anal Anastomosis (IPAA) to Time of First Excisional Polypectomy of a Rectal Polyp Post IPAA | 152.7 months | Standard Deviation 42.1 |
Comparison: Time to FAP-related surgical events (months); 25th percentile. Index date based on most recent colon and or rectum adenomatous polyps evaluation, most recent duodenal adenomatous polyps evaluation, and most recent desmoids tumors evaluation for Matched Control, Not Matched Celecoxib, and All Celecoxib Treated, respectively.95% CI: [104.73, 183.48]
Comparison: Time to FAP-related surgical events (months); 25th percentile.95% CI: [104.73, 183.48]
Primary
Time From Ileorectal Anastomosis (IRA) to Time of First Excisional Polypectomy of a Rectal Polyp Post IRA
Time(months): \[date of first excisional polypectomy of rectal polyp post IRA minus date of prior IRA plus 1\] divided by 30.44. Baseline = start of study follow-up: start of on-study celecoxib treatment period for celecoxib-treated subjects and comparable to index date for control subjects. Index date calculated as Matched Celecoxib-treated patients: number of days from most recent FAP-related surgery (IRA or IPAA) to start of study follow-up; add this number of days to matched control patient's most recent FAP-related surgery date=index date for Matched Control.
Time frame: Up to 8 years prior to baseline
Population: All eligible subjects with IRA performed prior to start of study follow-up; first excisional polypectomy of rectal polyp post IRA. Polyp size unavailable for many subjects; not considered in analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Matched Celecoxib Treated | Time From Ileorectal Anastomosis (IRA) to Time of First Excisional Polypectomy of a Rectal Polyp Post IRA | 86.4 months | Standard Deviation 143.78 |
| Matched Control | Time From Ileorectal Anastomosis (IRA) to Time of First Excisional Polypectomy of a Rectal Polyp Post IRA | 4.0 months | Standard Deviation 3.25 |
| Not Matched Celecoxib Treated | Time From Ileorectal Anastomosis (IRA) to Time of First Excisional Polypectomy of a Rectal Polyp Post IRA | 78.4 months | Standard Deviation 102.01 |
| All Celecoxib Treated | Time From Ileorectal Anastomosis (IRA) to Time of First Excisional Polypectomy of a Rectal Polyp Post IRA | 79.5 months | Standard Deviation 105.44 |
Comparison: Time to FAP-related surgical events (months); twenty-fifth (25th) percentile presented due to limited number of subjects.~Index date based on most recent colon and or rectum adenomatous polyps evaluation, most recent duodenal adenomatous polyps evaluation, and most recent desmoids tumors evaluation for Matched Control, Not Matched Celecoxib, and All Celecoxib Treated, respectively.~Only 13 matched pairs identified: p-values not computed in analysis of time-to-event endpoints95% CI: [3.48, 301.64]
Comparison: Time to FAP-related surgical events (months); 25th percentile.95% CI: [3.48, 11.76]
Comparison: Time to FAP-related surgical events (months); 25th percentile.95% CI: [3.48, 14.49]
Primary
Time From Start of Study Follow-up to the Time of First Excisional Polypectomy of a Rectal Polyp Post IRA
Time(months): \[date of first excisional polypectomy of rectal polyp post IRA minus date of start of study follow-up plus 1\] divided by 30.44.
Time frame: Baseline, Up to 60 months post-baseline
Population: All eligible subjects with IRA performed prior to start of study follow-up included, except left-censored subjects (had first excisional polypectomy of rectal polyp post IRA prior to start of study follow-up). No control group subjects (n=3) had a post-IRA polypectomy (no data).
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Matched Celecoxib Treated | Time From Start of Study Follow-up to the Time of First Excisional Polypectomy of a Rectal Polyp Post IRA | 19.8 months | Full Range 17.14 |
| Not Matched Celecoxib Treated | Time From Start of Study Follow-up to the Time of First Excisional Polypectomy of a Rectal Polyp Post IRA | 32.1 months | — |
| All Celecoxib Treated | Time From Start of Study Follow-up to the Time of First Excisional Polypectomy of a Rectal Polyp Post IRA | 25.9 months | — |
Comparison: Time to FAP-related surgical events (months); 25th percentile.95% CI: [0, 33.77]
Comparison: Time to FAP-related surgical events (months); 25th percentile.95% CI: [0, 33.77]
Primary
Time From Start of Study Follow-up to Time of First Excisional Polypectomy of a Rectal Polyp Post IPAA
Time (months): \[date of first excisional polypectomy of rectal polyp post IPAA minus date of start of study follow-up plus 1\] divided by 30.44.
Time frame: Baseline, Up to 60 months post-baseline
Population: All eligible subjects with IPAA performed prior to start of study follow-up included, except left-censored subjects (had first excisional polypectomy post IPAA prior to start of study follow-up). No control group subjects (n=7) had a post-IPAA polypectomy (no data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Matched Celecoxib Treated | Time From Start of Study Follow-up to Time of First Excisional Polypectomy of a Rectal Polyp Post IPAA | 20.3 months | Standard Deviation 15.72 |
| All Celecoxib Treated | Time From Start of Study Follow-up to Time of First Excisional Polypectomy of a Rectal Polyp Post IPAA | 20.3 months | Standard Deviation 15.72 |
Comparison: Time to FAP-related surgical events (months); 25th percentile.95% CI: [9.07, 38.24]
Secondary
Duodenal Adenoma Burden as Measured by Spigelman Stage
Number of subjects with polyp burden as assessed in most recent prior polyps evaluation: Spigelman stage provides index of disease severity based on number of polyps, polyp size, histology, and dysplasia; range is Stage 0 (none) to Stage IV (severe). EOS: endoscopic examination closest to end of on-study celecoxib or index period (within 6 months of end of celecoxib or index period and prior to intake of any exclusionary medications after baseline). Spigelman Stage not completed as staging data largely missing; see measure: Duodenal adenoma burden as measured by polyp counts.
Time frame: Baseline, 6 to 14 months post-baseline, End of study (EOS)
Population: All subjects; Spigelman Stage not completed as staging data largely missing.
Secondary
Rectal or Pouch Adenoma Burden Based on Polyp Counts
Number of subjects with polyp burden as assessed in most recent prior polyps evaluation: attenuated: \<100 polyps, mild: between 100 to 1000 polyps, severe: \>1000 polyps. EOS: endoscopic examination closest to end of on-study celecoxib or index period (within 6 months of end of celecoxib or index period and prior to intake of any exclusionary medications after baseline).
Time frame: Baseline, 6 to 14 months post-baseline, EOS
Population: All subjects; duodenal polyp burden analyzed in terms of severity categories and based on polyp numbers.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline unknown | 0 particpants |
| Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline severe | 0 particpants |
| Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline not assessed | 0 particpants |
| Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS not assessed | 0 particpants |
| Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline mild | 0 particpants |
| Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline attenuated | 6 particpants |
| Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS unknown | 3 particpants |
| Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS severe | 0 particpants |
| Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline severe | 0 particpants |
| Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline attenuated | 9 particpants |
| Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS mild | 0 particpants |
| Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS attenuated | 8 particpants |
| Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline unknown | 1 particpants |
| Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS no polyps | 2 particpants |
| Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline not assessed | 3 particpants |
| Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline no polyps | 4 particpants |
| Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline no polyps | 1 particpants |
| Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline mild | 2 particpants |
| Matched Control | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline severe | 0 particpants |
| Matched Control | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline attenuated | 4 particpants |
| Matched Control | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline mild | 2 particpants |
| Matched Control | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline unknown | 0 particpants |
| Matched Control | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline no polyps | 6 particpants |
| Matched Control | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline not assessed | 1 particpants |
| Matched Control | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline attenuated | 3 particpants |
| Matched Control | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline mild | 0 particpants |
| Matched Control | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline severe | 0 particpants |
| Matched Control | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline unknown | 0 particpants |
| Matched Control | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline no polyps | 5 particpants |
| Matched Control | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline not assessed | 5 particpants |
| Matched Control | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS attenuated | 2 particpants |
| Matched Control | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS mild | 0 particpants |
| Matched Control | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS severe | 0 particpants |
| Matched Control | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS unknown | 0 particpants |
| Matched Control | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS no polyps | 6 particpants |
| Matched Control | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS not assessed | 5 particpants |
| Not Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline no polyps | 4 particpants |
| Not Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline unknown | 0 particpants |
| Not Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline no polyps | 1 particpants |
| Not Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline unknown | 12 particpants |
| Not Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS not assessed | 26 particpants |
| Not Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline not assessed | 29 particpants |
| Not Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS no polyps | 2 particpants |
| Not Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS attenuated | 12 particpants |
| Not Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline severe | 0 particpants |
| Not Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS mild | 0 particpants |
| Not Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline attenuated | 18 particpants |
| Not Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS severe | 0 particpants |
| Not Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline mild | 2 particpants |
| Not Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline attenuated | 10 particpants |
| Not Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline not assessed | 5 particpants |
| Not Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline mild | 1 particpants |
| Not Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS unknown | 1 particpants |
| Not Matched Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline severe | 0 particpants |
| All Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline attenuated | 16 particpants |
| All Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS unknown | 4 particpants |
| All Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS mild | 0 particpants |
| All Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline unknown | 0 particpants |
| All Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline unknown | 13 particpants |
| All Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline attenuated | 27 particpants |
| All Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline mild | 4 particpants |
| All Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline no polyps | 5 particpants |
| All Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline no polyps | 5 particpants |
| All Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS not assessed | 26 particpants |
| All Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS severe | 0 particpants |
| All Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline not assessed | 32 particpants |
| All Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline severe | 0 particpants |
| All Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Baseline not assessed | 5 particpants |
| All Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline severe | 0 particpants |
| All Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS attenuated | 20 particpants |
| All Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | Post-baseline mild | 1 particpants |
| All Celecoxib Treated | Rectal or Pouch Adenoma Burden Based on Polyp Counts | EOS no polyps | 4 particpants |
Secondary
Time From Most Recent Prior FAP-related Surgical Event or Onset of FAP Phenotype to Time of First Excisional or Ablational Event for Rectal, Colonic, Pouch, or Duodenal Adenomas (Duodenal Adenomatous Polyps)
Time (months): \[date of first excisional or ablational event for colonic, pouch, or duodenal adenomas occuring after date of most recent prior FAP-related surgical event or date of FAP diagnosis minus date of most recent prior FAP-related surgical event or date of FAP diagnosis plus 1\] divided by 30.44.
Time frame: Up to 15 years prior to baseline
Population: All eligible subjects; first excisional or ablational event for rectal adenomas that does not qualify for primary efficacy endpoint; after most recent FAP-related surgical event prior to start of study follow-up or onset of FAP phenotype for subjects with no prior FAP-related surgery.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Matched Celecoxib Treated | Time From Most Recent Prior FAP-related Surgical Event or Onset of FAP Phenotype to Time of First Excisional or Ablational Event for Rectal, Colonic, Pouch, or Duodenal Adenomas (Duodenal Adenomatous Polyps) | 25.7 months | Standard Deviation 18.71 |
| Matched Control | Time From Most Recent Prior FAP-related Surgical Event or Onset of FAP Phenotype to Time of First Excisional or Ablational Event for Rectal, Colonic, Pouch, or Duodenal Adenomas (Duodenal Adenomatous Polyps) | 47.7 months | Standard Deviation 42.32 |
| Not Matched Celecoxib Treated | Time From Most Recent Prior FAP-related Surgical Event or Onset of FAP Phenotype to Time of First Excisional or Ablational Event for Rectal, Colonic, Pouch, or Duodenal Adenomas (Duodenal Adenomatous Polyps) | 89.9 months | Standard Deviation 89.34 |
| All Celecoxib Treated | Time From Most Recent Prior FAP-related Surgical Event or Onset of FAP Phenotype to Time of First Excisional or Ablational Event for Rectal, Colonic, Pouch, or Duodenal Adenomas (Duodenal Adenomatous Polyps) | 77.4 months | Standard Deviation 84.32 |
Comparison: Time to FAP-related surgical events (months); 25th percentile.95% CI: [8.05, 48.03]
Comparison: Time to FAP-related surgical events (months); 25th percentile.95% CI: [8.31, 105.68]
Comparison: Time to FAP-related surgical events (months); 25th percentile.95% CI: [16.03, 56.34]
Comparison: Time to FAP-related surgical events (months); 25th percentile.95% CI: [12.35, 40.31]
Secondary
Time From Most Recent Prior FAP-related Surgical Event or Onset of FAP Phenotype to Time of First FAP-related Adverse Event
Time (months): \[date of first FAP-related adverse event, occurring after the date of most recent prior FAP-related surgery, or date of FAP diagnosis minus date of most recent prior FAP-related surgery, or date of FAP diagnosis plus 1\] divided by 30.44. FAP-related adverse event defined as any FAP related cancers, desmoid tumors requiring procedural intervention, hospitalizations or procedural interventions, or death related to FAP (i.e., as a consequence of FAP, FAP complications, or a procedure or drug used to treat FAP-related medical problems).
Time frame: Up to 15 years prior to baseline
Population: All eligible subjects; first FAP-related adverse event (FAP-related cancers, desmoid tumors requiring procedural intervention, hospitalizations, procedural interventions, or death related to FAP) after subject's most recent FAP-related surgical event performed prior to start of study follow-up, onset of FAP phenotype (no prior FAP-related surgery).
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Matched Celecoxib Treated | Time From Most Recent Prior FAP-related Surgical Event or Onset of FAP Phenotype to Time of First FAP-related Adverse Event | 3.0 months | Full Range 123.17 |
| Matched Control | Time From Most Recent Prior FAP-related Surgical Event or Onset of FAP Phenotype to Time of First FAP-related Adverse Event | 3.4 months | Full Range 48.34 |
| Not Matched Celecoxib Treated | Time From Most Recent Prior FAP-related Surgical Event or Onset of FAP Phenotype to Time of First FAP-related Adverse Event | 61.4 months | — |
| All Celecoxib Treated | Time From Most Recent Prior FAP-related Surgical Event or Onset of FAP Phenotype to Time of First FAP-related Adverse Event | 56.3 months | — |
Comparison: Time to FAP-related events (months); 25th percentile.95% CI: [4.07, 64.16]
Comparison: Time to FAP-related events (months); 25th percentile.95% CI: [3.68, 64.16]
Secondary
Time From Post IRA to Time of Conversion From IRA to IPAA
Time (months): \[date of IPAA minus date of prior IRA plus 1\] divided by 30.44.
Time frame: Up to 15 years prior to baseline
Population: All eligible subjects with IRA performed prior to start of study follow-up; data censored (n=5) for control group subjects (no data).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Matched Celecoxib Treated | Time From Post IRA to Time of Conversion From IRA to IPAA | 301.6 months |
| Not Matched Celecoxib Treated | Time From Post IRA to Time of Conversion From IRA to IPAA | 129.7 months |
| All Celecoxib Treated | Time From Post IRA to Time of Conversion From IRA to IPAA | 175.8 months |
Secondary
Time From Start of Study Follow-up to Time of Conversion From IRA to IPAA
Time (months): \[date of IPAA minus date of start of study follow-up plus 1\] divided by 30.44.
Time frame: Baseline, Up to 60 months post-baseline
Population: All eligible subjects with IRA performed prior to start of study follow-up included, except left-censored subjects (had IPAA prior to start of study follow-up); data censored (n=5) for control group subjects (no data).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Not Matched Celecoxib Treated | Time From Start of Study Follow-up to Time of Conversion From IRA to IPAA | 4.8 months |
| All Celecoxib Treated | Time From Start of Study Follow-up to Time of Conversion From IRA to IPAA | 4.8 months |
Secondary
Time From Start of Study Follow-up to Time of First Excisional or Ablational Event for Rectal, Colonic, Pouch, or Duodenal Adenomas
Time (months): \[date of first excisional or ablational event for colonic, pouch, or duodenal adenomas, occurring after date of most recent prior FAP-related surgical event, or date of FAP diagnosis minus date of start of study follow-up plus 1\] divided by 30.44.
Time frame: Baseline, Up to 60 months post-baseline
Population: All eligible subjects included, except left censored subjects (had any excisional or ablational event for rectal, colonic, pouch, or duodenal adenomas between date of most recent FAP-related surgical event performed prior to the start of study follow-up, or onset of FAP phenotype \[with no prior FAP-related surgery\], and start of study follow-up).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Matched Celecoxib Treated | Time From Start of Study Follow-up to Time of First Excisional or Ablational Event for Rectal, Colonic, Pouch, or Duodenal Adenomas | 0.0 months | Standard Deviation 0 |
| Matched Control | Time From Start of Study Follow-up to Time of First Excisional or Ablational Event for Rectal, Colonic, Pouch, or Duodenal Adenomas | 41.7 months | Standard Deviation 21.73 |
| Not Matched Celecoxib Treated | Time From Start of Study Follow-up to Time of First Excisional or Ablational Event for Rectal, Colonic, Pouch, or Duodenal Adenomas | 21.4 months | Standard Deviation 22.39 |
| All Celecoxib Treated | Time From Start of Study Follow-up to Time of First Excisional or Ablational Event for Rectal, Colonic, Pouch, or Duodenal Adenomas | 12.9 months | Standard Deviation 19.71 |
Secondary
Time From Start of Study Follow-up to Time of First FAP-related Adverse Event
Time (months): \[date of first FAP-related adverse event, occurring after the date of the most recent prior FAP-related surgery, or date of FAP diagnosis minus date of start of study follow-up plus 1\] divided by 30.44. FAP-related adverse event defined as any FAP related cancers, desmoid tumors requiring procedural intervention, hospitalizations or procedural interventions, or death related to FAP (i.e., as a consequence of FAP, FAP complications, or a procedure or drug used to treat FAP-related medical problems).
Time frame: Baseline, Up to 60 months post-baseline
Population: All eligible subjects included, except left-censored subjects (had any FAP-related adverse event between the date of most recent FAP-related surgical event performed prior to start of study follow-up, or onset of FAP phenotype (no prior FAP-related surgery), and start of study follow-up.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Matched Celecoxib Treated | Time From Start of Study Follow-up to Time of First FAP-related Adverse Event | 37.9 months |
| Matched Control | Time From Start of Study Follow-up to Time of First FAP-related Adverse Event | 75.7 months |
| Not Matched Celecoxib Treated | Time From Start of Study Follow-up to Time of First FAP-related Adverse Event | 9.7 months |
| All Celecoxib Treated | Time From Start of Study Follow-up to Time of First FAP-related Adverse Event | 14.3 months |
Post Hoc
Duodenal Adenoma Burden as Measured by Polyp Counts
Number of subjects with polyp burden as assessed in most recent prior polyps evaluation: attenuated: \<100 polyps, mild: between 100 to 1000 polyps, severe: \>1000 polyps. EOS: endoscopic examination closest to end of on-study celecoxib or index period (within 6 months of end of celecoxib or index period and prior to intake of any exclusionary medications after baseline). Post-hoc analysis of duodenal polyp burden in terms of severity categories and based on polyp numbers; Spigelman Stage not completed as staging data largely missing (see: Duodenal adenoma burden as measured by Spigelman Stage)
Time frame: Baseline, 6 to 14 months post-baseline, End of study (EOS)
Population: All subjects; Spigelman Stage not completed as staging data largely missing; duodenal polyp burden analyzed in terms of severity categories and based on polyp numbers.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS attenuated | 2 participants |
| Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS not assessed | 9 participants |
| Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline no polyps | 1 participants |
| Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline no polyps | 1 participants |
| Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline unknown | 3 participants |
| Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline attenuated | 5 participants |
| Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS unknown | 1 participants |
| Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline not assessed | 4 participants |
| Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline severe | 0 participants |
| Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline not assessed | 8 participants |
| Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS no polyps | 1 participants |
| Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline attenuated | 1 participants |
| Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline mild | 0 participants |
| Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline severe | 0 participants |
| Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS mild | 0 participants |
| Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline mild | 0 participants |
| Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS severe | 0 participants |
| Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline unknown | 3 participants |
| Matched Control | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS no polyps | 1 participants |
| Matched Control | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline severe | 0 participants |
| Matched Control | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline unknown | 0 participants |
| Matched Control | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline mild | 0 participants |
| Matched Control | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline not assessed | 7 participants |
| Matched Control | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline no polyps | 3 participants |
| Matched Control | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS not assessed | 10 participants |
| Matched Control | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline severe | 0 participants |
| Matched Control | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline unknown | 2 participants |
| Matched Control | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS unknown | 0 participants |
| Matched Control | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline no polyps | 5 participants |
| Matched Control | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline not assessed | 5 participants |
| Matched Control | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline attenuated | 1 participants |
| Matched Control | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS mild | 0 participants |
| Matched Control | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline attenuated | 3 participants |
| Matched Control | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS severe | 0 participants |
| Matched Control | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline mild | 0 participants |
| Matched Control | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS attenuated | 2 participants |
| Not Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS unknown | 2 participants |
| Not Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS severe | 0 participants |
| Not Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline attenuated | 18 participants |
| Not Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline mild | 0 participants |
| Not Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline severe | 0 participants |
| Not Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline unknown | 10 participants |
| Not Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline no polyps | 5 participants |
| Not Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline not assessed | 8 participants |
| Not Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline attenuated | 12 participants |
| Not Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline mild | 0 participants |
| Not Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline severe | 0 participants |
| Not Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline unknown | 0 participants |
| Not Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline no polyps | 0 participants |
| Not Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline not assessed | 29 participants |
| Not Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS attenuated | 17 participants |
| Not Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS mild | 0 participants |
| Not Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS no polyps | 2 participants |
| Not Matched Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS not assessed | 20 participants |
| All Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline mild | 0 participants |
| All Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS mild | 0 participants |
| All Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS attenuated | 19 participants |
| All Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline attenuated | 13 participants |
| All Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline not assessed | 12 participants |
| All Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS severe | 0 participants |
| All Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline no polyps | 6 participants |
| All Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline unknown | 13 participants |
| All Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline severe | 0 participants |
| All Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS unknown | 3 participants |
| All Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline mild | 0 participants |
| All Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Baseline attenuated | 23 participants |
| All Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS not assessed | 29 participants |
| All Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline no polyps | 1 participants |
| All Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline unknown | 3 participants |
| All Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | EOS no polyps | 3 participants |
| All Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline not assessed | 37 participants |
| All Celecoxib Treated | Duodenal Adenoma Burden as Measured by Polyp Counts | Post-baseline severe | 0 participants |