Crohn's Disease
Conditions
Brief summary
To make adalimumab available to subjects suffering from moderately to severely active Crohn's Disease (CD) and to expand the safety information on adalimumab. The study also assessed changes in Patient Reported Outcome Measures from baseline.
Detailed description
This was a Phase 3, multicenter, open-label, Early Access Study with an induction regimen of adalimumab 160 mg subcutaneous (SC) at Baseline and 80 mg SC at Week 2, followed by maintenance dosing of 40 mg every other week (eow) starting at Week 4 in subjects with moderately to severely active Crohn's Disease (CD) who were eligible to receive biologic therapy or who had failed to respond to, lost response to, or were intolerant to infliximab. Failure of prior therapy was determined by the Investigator. Subjects were to have an 8-week wash-out period prior to Baseline from the last dose of infliximab.
Interventions
BIOLOGICALadalimumab
160 mg loading dose, 80 mg at week 2, 40 mg every other week
Sponsors
Abbott
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males or females 18 years of age and older * Females: Not of childbearing potential OR Practicing approved birth control throughout the study and for 150 days after study completion * Diagnosis of moderate to severe CD for greater than 16 weeks prior to screening; Crohn's Disease Activity Index score \> 220 OR Harvey Bradshaw Index equal to or higher than 7, and who are refractory to optimal conventional therapies such as, 5-aminosalicylic acid (5-ASA), glucocorticoids, and immunosuppressive therapies (azathioprine, 6-MP and MTX) * Subjects who failed prior infliximab therapy (as determined by the primary investigator), including those who never clinically responded (primary non-responders)
Exclusion criteria
* History of cancer other than some skin and cervical cancers * History of opportunistic infections, central nervous system (CNS) demyelinating disease, chronic viral hepatitis, or untreated tuberculosis * Subjects with other, poorly controlled medical conditions * Subjects with any prior exposure to Tysabri® (natalizumab) * Subjects who have received any investigational agent in the past 30 days or 5 half-lives prior to screening (whichever is longer) * Female subjects who are pregnant or breast-feeding or considering becoming pregnant during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Extent of Exposure - Duration in Days | Up to 24 weeks | Extent of exposure for all adalimumab treated subjects |
| Total Number of Injections of Adalimumab | Up to 24 weeks | Extent of exposure for all adalimumab treated subjects |
| Compliance With Number of Injections of Adalimumab. Compliance Corresponds to Patients Who Received Their Injections. | Up to 24 weeks | Treatment compliance (%) = 100 \* (Number of doses of study medication actually received)/(Number of doses planned during the subject's participation in the study). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 50% Improvement in Draining Fistula Count and Fistula Healing | Week 12, Week 24, Last Assessment Value (last nonmissing value) | Decrease in draining fistula is beneficial. 50 percent improvement refers to a reduction in the number of baseline fistula by 50 percent. |
| Work Productivity and Activity Impairment - Change From Baseline in Overall Work Impairment | Weeks 4, 8, 12, and 24, and Last Assessment Value (last nonmissing value) | Scores are expressed as impairment percentages, higher numbers indicate greater impairment and less productivity (0% = no impairment; 100% = total loss of work productivity). Minimal clinically important difference = 7 points. Measure is Mean percent change. |
| Hematology - Change From Baseline to Final Visit | Up to 24 weeks | Changes from the Group mean at baseline are compared to the final visit Group mean value |
| Clinical Chemistry - Change From Baseline to Final Visit | Up to 24 weeks | Changes from the Group mean at Baseline are compared to the final visit Group mean value |
| Fistula Count Mean Change From Baseline (Change in Number of Fistulas From Baseline). | Week 12, Week 24, and Last Assessment Value (last nonmissing value) | Draining fistula counts is the sum of abdominal and perianal fistulas for each subject at each visit. |
| Work Productivity and Activity Impairment - Change From Baseline in Absenteeism | Weeks 4, 8, 12, and 24, and Last Assessmentl Value (last nonmissing value) | The Work Productivity and Activity Impairment (WPAI) questionnaire is a validated, self-administered tool used to assess the impact of disease on productivity. There are four component scores for WPAI: absenteeism, presenteeism, total work productivity impairment, daily activity impairment. The score for each component ranges from 0% to 100% (0%=no impairment; 100%=total loss of work productivity or activity). The minimal clinically important difference (MCID) is an absolute change of 7%. |
| Work Productivity and Activity Impairment - Change From Baseline in Presenteeism | Weeks 4, 8, 12, and 24, and Last Assessment Value (last nonmissing value) | The Work Productivity and Activity Impairment (WPAI) questionnaire is a validated, self-administered tool used to assess the impact of disease on productivity. There are four component scores for WPAI: absenteeism, presenteeism, total work productivity impairment, daily activity impairment. The score for each component ranges from 0% to 100% (0%=no impairment; 100%=total loss of work productivity or activity). The minimal clinically important difference (MCID) is an absolute change of 7%. |
| Work Productivity and Activity Impairment - Change From Baseline in Activity Impairment | Weeks 4, 8, 12, and 24, and Last Assessment Value (last nonmissing value) | The Work Productivity and Activity Impairment (WPAI) questionnaire is a validated, self-administered tool used to assess the impact of disease on productivity. There are four component scores for WPAI: absenteeism, presenteeism, total work productivity impairment, daily activity impairment. The score for each component ranges from 0% to 100% (0%=no impairment; 100%=total loss of work productivity or activity). The minimal clinically important difference (MCID) is an absolute change of 7%. |
| Urinalysis - Change From Baseline to Final Visit | Up to 24 weeks | Changes from the Group mean at baseline are compared to the final visit Group mean value |
| Overall Health Care Resource Utilization | Up to 24 weeks | From the Overall Health Care Resource Utilization Questionnaire: Number visits to physician, number visits to Emergency Room, number of hospital admissions, number of days of hospitalization. |
| Employment Status: Number of Subjects Employed | Baseline, Weeks 4, 8, 12, and 24, and Last Assessment Value (last nonmissing value) | Summary of employment status of those employed. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 40 mg Adalimumab Every Other Week Induction regimen of adalimumab 160 mg subcutaneous (SC) at Baseline and 80 mg SC at Week 2, followed by maintenance dosing of 40 mg every other week (eow) starting at Week 4 | 304 |
| Total | 304 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 26 |
| Overall Study | Adverse Event + Hospitalization | 1 |
| Overall Study | Adverse Event + Lost Response | 1 |
| Overall Study | Adverse Event + No Response | 1 |
| Overall Study | Adverse Event + No Therapeutic Benefit | 1 |
| Overall Study | Adverse Event + Withdrawn from Study | 1 |
| Overall Study | Adverse Event + Withdrew Consent | 1 |
| Overall Study | Adverse Event + Worsening of CD | 1 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Other reason not specified | 10 |
| Overall Study | Withdrawal by Subject | 4 |
| Overall Study | Withdrew Consent + Lack of Efficacy | 1 |
Baseline characteristics
| Characteristic | 40 mg Adalimumab Every Other Week |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 296 Participants |
| Alcohol Ex-User | 15 participants |
| Alcohol Non-User | 142 participants |
| Alcohol User | 147 participants |
| C-Reactive protein mg/dL < 1.0 mg/dL | 148 participants |
| C-Reactive protein mg/dL > = 1.0 mg/dL | 155 participants |
| C-Reactive protein mg/dL Missing | 1 participants |
| Duration of Crohn's Disease at Screening in Years | 11.8 years STANDARD_DEVIATION 9.54 |
| Nicotine Ex-User | 84 participants |
| Nicotine Non-User | 122 participants |
| Nicotine User | 98 participants |
| Number of Subjects with Abdominal Fistulas at Screening Count 0 | 291 Participants |
| Number of Subjects with Abdominal Fistulas at Screening Count 1 | 10 Participants |
| Number of Subjects with Abdominal Fistulas at Screening Count 2 | 1 Participants |
| Number of Subjects with Abdominal Fistulas at Screening Count 3 | 0 Participants |
| Number of Subjects with Abdominal Fistulas at Screening Count >=4 | 1 Participants |
| Number of Subjects with Abdominal Fistulas at Screening Missing | 1 Participants |
| Number Subjects With Draining Cutaneous Fistulas at Screening Count 0 lesions | 235 participants |
| Number Subjects With Draining Cutaneous Fistulas at Screening Count 1 lesion | 42 participants |
| Number Subjects With Draining Cutaneous Fistulas at Screening Count 2 lesions | 16 participants |
| Number Subjects With Draining Cutaneous Fistulas at Screening Count 3 lesions | 5 participants |
| Number Subjects With Draining Cutaneous Fistulas at Screening Count >=4 lesions | 5 participants |
| Number Subjects With Draining Cutaneous Fistulas at Screening Missing | 1 participants |
| Number Subjects with Perianal Fistulas at Screening Count 0 | 244 Participants |
| Number Subjects with Perianal Fistulas at Screening Count 1 | 35 Participants |
| Number Subjects with Perianal Fistulas at Screening Count 2 | 17 Participants |
| Number Subjects with Perianal Fistulas at Screening Count 3 | 4 Participants |
| Number Subjects with Perianal Fistulas at Screening Count >=4 | 3 Participants |
| Number Subjects with Perianal Fistulas at Screening Missing | 1 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 participants |
| Race/Ethnicity, Customized Asian | 3 participants |
| Race/Ethnicity, Customized Black or African American | 1 participants |
| Race/Ethnicity, Customized Hispanic | 0 participants |
| Race/Ethnicity, Customized More than one race | 1 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 6 participants |
| Race/Ethnicity, Customized White | 291 participants |
| Region of Enrollment Canada | 304 Participants |
| Sex: Female, Male Female | 173 Participants |
| Sex: Female, Male Male | 131 Participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Anal/Perianal | 2 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Anal/Perianal + Colon | 6 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Anal/Perianal + Colon + GD + Ileum | 4 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Anal/Perianal + Colon + GD +Rectum + Ileum | 2 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Anal/Perianal+Colon+GD+Rectum+Jejunum+Ileum | 1 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Anal/Perianal + Colon + Ileum | 13 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Anal/Perianal + Colon + Ileum + Other | 3 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Anal/Perianal + Colon + Jejunum + Ileum | 3 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Anal/Perianal + Colon + Other | 2 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Anal/Perianal + Colon + Rectum | 3 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Anal/Perianal + Colon + Rectum + Ileum | 13 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Anal/Perianal + Colon + Rectum + Ileum + Other | 2 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Anal/Perianal + Colon + Rectum +Jejunum + Ileum | 1 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Anal/Perianal + Ileum | 16 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Anal/Perianal + Ileum + Other | 2 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Anal/Perianal + Jejunum + Ileum | 1 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Anal/Perianal + Rectum | 2 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Anal/Perianal + Rectum + Ileum | 3 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Anal/Perianal + Rectum + Other | 1 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Colon | 40 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Colon + Gastroduodenum + Ileum | 1 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Colon+GD+Jejunum+Ileum | 2 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Colon+GD+Rectum+Jejunum+Ileum | 1 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Colon+GD+Rectum+ Other | 1 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Colon + Ileum | 64 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Colon + Ileum + Other | 3 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Colon + Jejunum + Ileum | 3 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Colon + Other | 2 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Colon + Rectum | 8 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Colon + Rectum + Ileum | 13 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Colon + Rectum + Ileum + Other | 2 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Gastroduodenum | 1 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Gastroduodenum + Ileum | 3 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Ileum | 54 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Ileum + Other | 7 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Jejunum | 2 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Jejunum + Ileum | 3 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Other | 3 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Rectum | 3 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Rectum + Ileum | 7 participants |
| Summary of Locations of Crohn's Disease at Screening (All Treated Subjects) Rectum + Ileum + Other | 1 participants |
| Weight in kilograms < = 70 kg | 163 Participants |
| Weight in kilograms > 70 kg | 141 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 133 / — |
| serious Total, serious adverse events | 44 / — |
Outcome results
Primary
Compliance With Number of Injections of Adalimumab. Compliance Corresponds to Patients Who Received Their Injections.
Treatment compliance (%) = 100 \* (Number of doses of study medication actually received)/(Number of doses planned during the subject's participation in the study).
Time frame: Up to 24 weeks
Population: In addition to the Intent To Treat population, summaries for outcome measures were provided for the analyzable subsets, and subjects in the Per-Protocol analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 40 mg Adalimumab Every Other Week | Compliance With Number of Injections of Adalimumab. Compliance Corresponds to Patients Who Received Their Injections. | 98.85 Percentage of injections | Standard Deviation 4.207 |
Primary
Mean Extent of Exposure - Duration in Days
Extent of exposure for all adalimumab treated subjects
Time frame: Up to 24 weeks
Population: In addition to the Intent To Treat population, summaries for outcome measures were provided for the analyzable subsets, and subjects in the Per-Protocol analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 40 mg Adalimumab Every Other Week | Mean Extent of Exposure - Duration in Days | 159.2 days | Standard Deviation 34.78 |
Primary
Total Number of Injections of Adalimumab
Extent of exposure for all adalimumab treated subjects
Time frame: Up to 24 weeks
Population: In addition to the Intent To Treat population, summaries for outcome measures were provided for the analyzable subsets, and subjects in the Per-Protocol analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 40 mg Adalimumab Every Other Week | Total Number of Injections of Adalimumab | Number of Injections During Induction Therapy | 2 injections | Standard Deviation 0.1 |
| 40 mg Adalimumab Every Other Week | Total Number of Injections of Adalimumab | Number of Injections During Maintenance Therapy | 11.8 injections | Standard Deviation 4.24 |
Secondary
50% Improvement in Draining Fistula Count and Fistula Healing
Decrease in draining fistula is beneficial. 50 percent improvement refers to a reduction in the number of baseline fistula by 50 percent.
Time frame: Week 12, Week 24, Last Assessment Value (last nonmissing value)
Population: Intent To Treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 40 mg Adalimumab Every Other Week | 50% Improvement in Draining Fistula Count and Fistula Healing | Week 12 50% Improvement in draining fistula | 35 participants |
| 40 mg Adalimumab Every Other Week | 50% Improvement in Draining Fistula Count and Fistula Healing | Week 24 50% Improvement in draining fistula | 31 participants |
| 40 mg Adalimumab Every Other Week | 50% Improvement in Draining Fistula Count and Fistula Healing | Last Value 50% Improvement in draining fistula | 32 participants |
| 40 mg Adalimumab Every Other Week | 50% Improvement in Draining Fistula Count and Fistula Healing | Week 12 Fistula Healing | 23 participants |
| 40 mg Adalimumab Every Other Week | 50% Improvement in Draining Fistula Count and Fistula Healing | Week 24 Fistula Healing | 27 participants |
| 40 mg Adalimumab Every Other Week | 50% Improvement in Draining Fistula Count and Fistula Healing | Last Assessment Value Fistula Healing | 28 participants |
Secondary
Clinical Chemistry - Change From Baseline to Final Visit
Changes from the Group mean at Baseline are compared to the final visit Group mean value
Time frame: Up to 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 40 mg Adalimumab Every Other Week | Clinical Chemistry - Change From Baseline to Final Visit | SGPT/ALT (U/L) | 0.6 number | Standard Deviation 17.89 |
| 40 mg Adalimumab Every Other Week | Clinical Chemistry - Change From Baseline to Final Visit | SGOT/ALT (U/L) | 1.6 number | Standard Deviation 10.35 |
| 40 mg Adalimumab Every Other Week | Clinical Chemistry - Change From Baseline to Final Visit | Alkaline phosphatase (U/L) | -5.2 number | Standard Deviation 21.53 |
| 40 mg Adalimumab Every Other Week | Clinical Chemistry - Change From Baseline to Final Visit | Total Bilirubin (mcmol/L) | 1.6 number | Standard Deviation 4.06 |
| 40 mg Adalimumab Every Other Week | Clinical Chemistry - Change From Baseline to Final Visit | Creatinine (mcmol/L) | 1.7 number | Standard Deviation 10.35 |
| 40 mg Adalimumab Every Other Week | Clinical Chemistry - Change From Baseline to Final Visit | BUN (mmol/L) | 0.06 number | Standard Deviation 1.367 |
| 40 mg Adalimumab Every Other Week | Clinical Chemistry - Change From Baseline to Final Visit | Uric acid (mcmol/L) | 4.6 number | Standard Deviation 52.38 |
| 40 mg Adalimumab Every Other Week | Clinical Chemistry - Change From Baseline to Final Visit | Inorganic phosphate | 0.016 number | Standard Deviation 0.2588 |
| 40 mg Adalimumab Every Other Week | Clinical Chemistry - Change From Baseline to Final Visit | Calcium (mmol/L) | 0.008 number | Standard Deviation 0.1189 |
| 40 mg Adalimumab Every Other Week | Clinical Chemistry - Change From Baseline to Final Visit | Sodium (mmol/L) | -0.3 number | Standard Deviation 2.38 |
| 40 mg Adalimumab Every Other Week | Clinical Chemistry - Change From Baseline to Final Visit | Potassium (mmol/L) | -0.00 number | Standard Deviation 0.779 |
| 40 mg Adalimumab Every Other Week | Clinical Chemistry - Change From Baseline to Final Visit | Albumin (G/L) | 0.4 number | Standard Deviation 4.01 |
| 40 mg Adalimumab Every Other Week | Clinical Chemistry - Change From Baseline to Final Visit | Total protein (G/L) | 0.8 number | Standard Deviation 4.83 |
| 40 mg Adalimumab Every Other Week | Clinical Chemistry - Change From Baseline to Final Visit | Cholesterol (mmol/L) | 0.021 number | Standard Deviation 0.7024 |
| 40 mg Adalimumab Every Other Week | Clinical Chemistry - Change From Baseline to Final Visit | Triglycerides (mmol/L) | 0.093 number | Standard Deviation 0.7581 |
| 40 mg Adalimumab Every Other Week | Clinical Chemistry - Change From Baseline to Final Visit | C-reactive protein (mg/L) | -8.181 number | Standard Deviation 28.7023 |
| 40 mg Adalimumab Every Other Week | Clinical Chemistry - Change From Baseline to Final Visit | Glucose - fasting (mmol/L) | -0.268 number | Standard Deviation 1.3893 |
Secondary
Employment Status: Number of Subjects Employed
Summary of employment status of those employed.
Time frame: Baseline, Weeks 4, 8, 12, and 24, and Last Assessment Value (last nonmissing value)
Population: In addition to the Intent To Treat population, summaries for outcome measures were provided for the analyzable subsets, and subjects in the Per-Protocol analysis set.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| 40 mg Adalimumab Every Other Week | Employment Status: Number of Subjects Employed | Baseline | 195 participants | 64.1 |
| 40 mg Adalimumab Every Other Week | Employment Status: Number of Subjects Employed | Week 4 | 199 participants | — |
| 40 mg Adalimumab Every Other Week | Employment Status: Number of Subjects Employed | Week 8 | 198 participants | — |
| 40 mg Adalimumab Every Other Week | Employment Status: Number of Subjects Employed | Week 12 | 192 participants | — |
| 40 mg Adalimumab Every Other Week | Employment Status: Number of Subjects Employed | Week 24 | 190 participants | — |
| 40 mg Adalimumab Every Other Week | Employment Status: Number of Subjects Employed | Last Assessment Value | 208 participants | — |
Secondary
Fistula Count Mean Change From Baseline (Change in Number of Fistulas From Baseline).
Draining fistula counts is the sum of abdominal and perianal fistulas for each subject at each visit.
Time frame: Week 12, Week 24, and Last Assessment Value (last nonmissing value)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 40 mg Adalimumab Every Other Week | Fistula Count Mean Change From Baseline (Change in Number of Fistulas From Baseline). | Week 12 | -0.17 number of fistulas | Standard Deviation 0.644 |
| 40 mg Adalimumab Every Other Week | Fistula Count Mean Change From Baseline (Change in Number of Fistulas From Baseline). | Week 24 | -0.15 number of fistulas | Standard Deviation 0.587 |
| 40 mg Adalimumab Every Other Week | Fistula Count Mean Change From Baseline (Change in Number of Fistulas From Baseline). | Last Assessment Value | -0.15 number of fistulas | Standard Deviation 0.567 |
Secondary
Hematology - Change From Baseline to Final Visit
Changes from the Group mean at baseline are compared to the final visit Group mean value
Time frame: Up to 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 40 mg Adalimumab Every Other Week | Hematology - Change From Baseline to Final Visit | Hemoglobin (g/L) | 2.2 number | Standard Deviation 12.43 |
| 40 mg Adalimumab Every Other Week | Hematology - Change From Baseline to Final Visit | Hematocrit (fraction) | 0.011 number | Standard Deviation 0.0376 |
| 40 mg Adalimumab Every Other Week | Hematology - Change From Baseline to Final Visit | Red blood cell count (x10^9/L) | 0.03 number | Standard Deviation 0.353 |
| 40 mg Adalimumab Every Other Week | Hematology - Change From Baseline to Final Visit | Platelet Count (x10^9/L) | -30.2 number | Standard Deviation 89.28 |
| 40 mg Adalimumab Every Other Week | Hematology - Change From Baseline to Final Visit | White blood cell count (x10^9/L) | -1.59 number | Standard Deviation 3.297 |
| 40 mg Adalimumab Every Other Week | Hematology - Change From Baseline to Final Visit | Neutrophils (x10^9/L) | -2.005 number | Standard Deviation 3.1777 |
| 40 mg Adalimumab Every Other Week | Hematology - Change From Baseline to Final Visit | Lymphocytes (x10^9/L) | 0.408 number | Standard Deviation 0.7285 |
| 40 mg Adalimumab Every Other Week | Hematology - Change From Baseline to Final Visit | Monocytes (x10^9/L) | -0.014 number | Standard Deviation 0.1725 |
| 40 mg Adalimumab Every Other Week | Hematology - Change From Baseline to Final Visit | Eosinophils (x10^9/L) | 0.009 number | Standard Deviation 0.1505 |
| 40 mg Adalimumab Every Other Week | Hematology - Change From Baseline to Final Visit | Basophils (x10^9/L) | -0.015 number | Standard Deviation 0.0617 |
Secondary
Overall Health Care Resource Utilization
From the Overall Health Care Resource Utilization Questionnaire: Number visits to physician, number visits to Emergency Room, number of hospital admissions, number of days of hospitalization.
Time frame: Up to 24 weeks
Population: In addition to the Intent To Treat population, summaries for outcome measures were provided for the analyzable subsets, and subjects in the Per-Protocol analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 40 mg Adalimumab Every Other Week | Overall Health Care Resource Utilization | Number of visits to a physician | 1.13 number of visits | Standard Deviation 2.794 |
| 40 mg Adalimumab Every Other Week | Overall Health Care Resource Utilization | Number of visits to Emergency Room | 0.17 number of visits | Standard Deviation 0.522 |
| 40 mg Adalimumab Every Other Week | Overall Health Care Resource Utilization | Number of hospital admissions | 0.10 number of visits | Standard Deviation 0.346 |
| 40 mg Adalimumab Every Other Week | Overall Health Care Resource Utilization | Number of days of hospitalizations | 0.60 number of visits | Standard Deviation 2.79 |
Secondary
Urinalysis - Change From Baseline to Final Visit
Changes from the Group mean at baseline are compared to the final visit Group mean value
Time frame: Up to 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 40 mg Adalimumab Every Other Week | Urinalysis - Change From Baseline to Final Visit | Urine pH | 0.02 number | Standard Deviation 0.98 |
| 40 mg Adalimumab Every Other Week | Urinalysis - Change From Baseline to Final Visit | Specific gravity | -0.0004 number | Standard Deviation 0.00713 |
Secondary
Work Productivity and Activity Impairment - Change From Baseline in Absenteeism
The Work Productivity and Activity Impairment (WPAI) questionnaire is a validated, self-administered tool used to assess the impact of disease on productivity. There are four component scores for WPAI: absenteeism, presenteeism, total work productivity impairment, daily activity impairment. The score for each component ranges from 0% to 100% (0%=no impairment; 100%=total loss of work productivity or activity). The minimal clinically important difference (MCID) is an absolute change of 7%.
Time frame: Weeks 4, 8, 12, and 24, and Last Assessmentl Value (last nonmissing value)
Population: In addition to the Intent To Treat population, summaries for outcome measures were provided for the analyzable subsets, and subjects in the Per-Protocol analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 40 mg Adalimumab Every Other Week | Work Productivity and Activity Impairment - Change From Baseline in Absenteeism | Week 4 | -5.99 units on a scale | Standard Deviation 24.592 |
| 40 mg Adalimumab Every Other Week | Work Productivity and Activity Impairment - Change From Baseline in Absenteeism | Week 8 | -7.55 units on a scale | Standard Deviation 27.543 |
| 40 mg Adalimumab Every Other Week | Work Productivity and Activity Impairment - Change From Baseline in Absenteeism | Week 12 | -8.74 units on a scale | Standard Deviation 33.477 |
| 40 mg Adalimumab Every Other Week | Work Productivity and Activity Impairment - Change From Baseline in Absenteeism | Week 24 | -8.54 units on a scale | Standard Deviation 27.26 |
| 40 mg Adalimumab Every Other Week | Work Productivity and Activity Impairment - Change From Baseline in Absenteeism | Last Assessment Value | -6.46 units on a scale | Standard Deviation 29.167 |
Secondary
Work Productivity and Activity Impairment - Change From Baseline in Activity Impairment
The Work Productivity and Activity Impairment (WPAI) questionnaire is a validated, self-administered tool used to assess the impact of disease on productivity. There are four component scores for WPAI: absenteeism, presenteeism, total work productivity impairment, daily activity impairment. The score for each component ranges from 0% to 100% (0%=no impairment; 100%=total loss of work productivity or activity). The minimal clinically important difference (MCID) is an absolute change of 7%.
Time frame: Weeks 4, 8, 12, and 24, and Last Assessment Value (last nonmissing value)
Population: In addition to the Intent To Treat population, summaries for outcome measures were provided for the analyzable subsets, and subjects in the Per-Protocol analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 40 mg Adalimumab Every Other Week | Work Productivity and Activity Impairment - Change From Baseline in Activity Impairment | Week 4 | -23.59 Units on scale | Standard Deviation 26.928 |
| 40 mg Adalimumab Every Other Week | Work Productivity and Activity Impairment - Change From Baseline in Activity Impairment | Week 8 | -24.79 Units on scale | Standard Deviation 28.431 |
| 40 mg Adalimumab Every Other Week | Work Productivity and Activity Impairment - Change From Baseline in Activity Impairment | Week 12 | -30.36 Units on scale | Standard Deviation 28.697 |
| 40 mg Adalimumab Every Other Week | Work Productivity and Activity Impairment - Change From Baseline in Activity Impairment | Week 24 | -34.00 Units on scale | Standard Deviation 29.552 |
| 40 mg Adalimumab Every Other Week | Work Productivity and Activity Impairment - Change From Baseline in Activity Impairment | Last Assessment Value | -30.98 Units on scale | Standard Deviation 30.484 |
Secondary
Work Productivity and Activity Impairment - Change From Baseline in Overall Work Impairment
Scores are expressed as impairment percentages, higher numbers indicate greater impairment and less productivity (0% = no impairment; 100% = total loss of work productivity). Minimal clinically important difference = 7 points. Measure is Mean percent change.
Time frame: Weeks 4, 8, 12, and 24, and Last Assessment Value (last nonmissing value)
Population: In addition to the Intent To Treat population, summaries for outcome measures were provided for the analyzable subsets, and subjects in the Per-Protocol analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 40 mg Adalimumab Every Other Week | Work Productivity and Activity Impairment - Change From Baseline in Overall Work Impairment | Week 4 | -22.08 Units on scale | Standard Deviation 28.454 |
| 40 mg Adalimumab Every Other Week | Work Productivity and Activity Impairment - Change From Baseline in Overall Work Impairment | Week 8 | -22.36 Units on scale | Standard Deviation 29.337 |
| 40 mg Adalimumab Every Other Week | Work Productivity and Activity Impairment - Change From Baseline in Overall Work Impairment | Week 12 | -29.93 Units on scale | Standard Deviation 33.669 |
| 40 mg Adalimumab Every Other Week | Work Productivity and Activity Impairment - Change From Baseline in Overall Work Impairment | Week 24 | -31.23 Units on scale | Standard Deviation 30.403 |
| 40 mg Adalimumab Every Other Week | Work Productivity and Activity Impairment - Change From Baseline in Overall Work Impairment | Last Assessment Value | -28.49 Units on scale | Standard Deviation 32.286 |
Secondary
Work Productivity and Activity Impairment - Change From Baseline in Presenteeism
The Work Productivity and Activity Impairment (WPAI) questionnaire is a validated, self-administered tool used to assess the impact of disease on productivity. There are four component scores for WPAI: absenteeism, presenteeism, total work productivity impairment, daily activity impairment. The score for each component ranges from 0% to 100% (0%=no impairment; 100%=total loss of work productivity or activity). The minimal clinically important difference (MCID) is an absolute change of 7%.
Time frame: Weeks 4, 8, 12, and 24, and Last Assessment Value (last nonmissing value)
Population: In addition to the ITT population, summaries for outcome measures were provided for the analyzable subsets, and subjects in the Per-Protocol analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 40 mg Adalimumab Every Other Week | Work Productivity and Activity Impairment - Change From Baseline in Presenteeism | Week 4 | -20.58 Units on scale | Standard Deviation 26.115 |
| 40 mg Adalimumab Every Other Week | Work Productivity and Activity Impairment - Change From Baseline in Presenteeism | Week 8 | -19.94 Units on scale | Standard Deviation 27.151 |
| 40 mg Adalimumab Every Other Week | Work Productivity and Activity Impairment - Change From Baseline in Presenteeism | Week 12 | -25.79 Units on scale | Standard Deviation 30.113 |
| 40 mg Adalimumab Every Other Week | Work Productivity and Activity Impairment - Change From Baseline in Presenteeism | Week 24 | -28.96 Units on scale | Standard Deviation 28.472 |
| 40 mg Adalimumab Every Other Week | Work Productivity and Activity Impairment - Change From Baseline in Presenteeism | Last Assessment Value | -26.69 Units on scale | Standard Deviation 30.058 |
Post Hoc
Harvey-Bradshaw Index (HBI) Mean Change From Baseline
HBI score (range 0-30) sum subtotal of 5 parameters of subject's CD activity: a)Well being 0=very well-4=terrible b) Abdominal pain 0=none- 3=severe c) Number liquid stools per day d) Abdominal mass 0=none-3=tender e) Complications: 1 point each. Decrease indicates improvement. Absolute decrease of 3 units on scale is clinically important.
Time frame: Weeks 4, 8, 12, and 24, and Last Assessment Value (last nonmissing value)
Population: Intent to Treat - subjects who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 40 mg Adalimumab Every Other Week | Harvey-Bradshaw Index (HBI) Mean Change From Baseline | Week 4 | -4.39 Units on scale | — |
| 40 mg Adalimumab Every Other Week | Harvey-Bradshaw Index (HBI) Mean Change From Baseline | Week 8 | -4.53 Units on scale | 95% Confidence Interval 5.175 |
| 40 mg Adalimumab Every Other Week | Harvey-Bradshaw Index (HBI) Mean Change From Baseline | Week 12 | -5.32 Units on scale | 95% Confidence Interval 5.008 |
| 40 mg Adalimumab Every Other Week | Harvey-Bradshaw Index (HBI) Mean Change From Baseline | Week 24 | -6.36 Units on scale | 95% Confidence Interval 5.031 |
| 40 mg Adalimumab Every Other Week | Harvey-Bradshaw Index (HBI) Mean Change From Baseline | Last Assessment Value | -5.92 Units on scale | 95% Confidence Interval 5.162 |
Post Hoc
Short Inflammatory Bowel Disease Questionnaire (SIBDQ) Mean Change From Baseline
Quality of life questionnaire for patients with IBD consisting of 4 domains: systemic, social, emotional, and bowel. This is a 10-item questionnaire, and all items are reported with a 7-point scale (ranging from 1 = poor HRQOL, to 7 = optimum HRQOL). Total SIBDQ score ranges from 10 (quality of life has been negatively affected tremendously by IBD) to 70 (quality of life is barely impacted by IBD). A change greater than 9 points was the minimal clinically important difference (MCID).
Time frame: Weeks 4, 8, 12, and 24, and Last Assessment Value (last nonmissing value)
Population: In addition to the Intent To Treat population, summaries for outcome measures were provided for the analyzable subsets, and subjects in the Per-Protocol analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 40 mg Adalimumab Every Other Week | Short Inflammatory Bowel Disease Questionnaire (SIBDQ) Mean Change From Baseline | Week 4 | 10.16 units on a scale | Standard Deviation 10.692 |
| 40 mg Adalimumab Every Other Week | Short Inflammatory Bowel Disease Questionnaire (SIBDQ) Mean Change From Baseline | Week 8 | 11.85 units on a scale | Standard Deviation 11.591 |
| 40 mg Adalimumab Every Other Week | Short Inflammatory Bowel Disease Questionnaire (SIBDQ) Mean Change From Baseline | Week 12 | 13.14 units on a scale | Standard Deviation 11.783 |
| 40 mg Adalimumab Every Other Week | Short Inflammatory Bowel Disease Questionnaire (SIBDQ) Mean Change From Baseline | Week 24 | 15.06 units on a scale | Standard Deviation 12.209 |
| 40 mg Adalimumab Every Other Week | Short Inflammatory Bowel Disease Questionnaire (SIBDQ) Mean Change From Baseline | Last Assessment Value | 13.74 units on a scale | Standard Deviation 12.629 |