Spondylarthropathies, Enthesitis
Conditions
Keywords
Refractory Heel Enthesitis in Spondylarthropathy, Spondylarthropathy, Refractory Heel Enthesitis
Brief summary
To assess the efficacy and safety of Etanercept in patients with spondylarthropathy and refractory heel enthesitis.
Interventions
DRUGEtanercept
50 mg injection once weekly
OTHERPlacebo
placebo
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Spondylarthropathy * Heel enthesitis refractory to standard treatment * Between 18 and 70 years of age * The patient global assessment of the disease activity (measured by a 100 mm VAS) must be \>40 in the last 48 hours
Exclusion criteria
* Use of \> 1 local steroid injection within 2 weeks of screening * Prior exposure to any TNF-inhibitor, including etanercept * Dose of NSAIDs changed within two weeks of study drug evaluation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Normalized Net Incremental Area Under the Curve (AUC) for Patient Global Assessment of Disease Activity (PGA) Between Randomization and Week 12 | 12 weeks | PGA was measured using a 100mm Visual Analog Scale (VAS) ranging from 0=very good to 100=very bad. The normalized net incremental area under the curve of the PGA is the area between the baseline and the PGA curve as a function of time (week 2, 4, 8, 12). AUC was computed using the linear trapezoidal method. All the areas above the baseline and under the curve are positive and all the area below the baseline and above the curve are negative. The net incremental AUC is the sum of these areas. This result is then divided by the study duration of the patients. (negative value = improvement). |
| Change From Baseline in Patient Global Assessment of Disease Activity Score at Week 12 | Baseline and 12 weeks | The patient global assessment of disease activity was measured using a 100mm Visual Analog Scale (VAS) ranging from 0=very good to 100=very bad. Change=12 week score minus baseline score. A negative score indicates an improvement in disease activity and a positive score indicates worsening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Achieving a 50% Response on the Patient Global Assessment of Disease Activity | 12 weeks | A response is defined as at least a 50% improvement (decrease) from baseline in the patient global assessment of disease activity. The patient global assessment of disease activity was measured using a 100mm Visual Analog Scale (VAS) ranging from 0=very good to 100=very bad. |
Countries
France, Germany, Netherlands
Participant flow
Recruitment details
Patients were recruited worldwide from February 2007 to June 2008.
Pre-assignment details
Patients were screened up to 6 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Etanercept 50mg subcutaneously once weekly | 12 |
| Placebo Subcutaneously once weekly | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 0 | 3 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Serious Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Etanercept | Placebo | Total |
|---|---|---|---|
| Age Continuous | 34.5 years STANDARD_DEVIATION 12.4 | 40.0 years STANDARD_DEVIATION 10.4 | 37.3 years STANDARD_DEVIATION 11.5 |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 12 | 11 / 12 |
| serious Total, serious adverse events | 1 / 12 | 0 / 12 |
Outcome results
Primary
Change From Baseline in Patient Global Assessment of Disease Activity Score at Week 12
The patient global assessment of disease activity was measured using a 100mm Visual Analog Scale (VAS) ranging from 0=very good to 100=very bad. Change=12 week score minus baseline score. A negative score indicates an improvement in disease activity and a positive score indicates worsening.
Time frame: Baseline and 12 weeks
Population: All randomized patients who received at least 1 dose of test article.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etanercept | Change From Baseline in Patient Global Assessment of Disease Activity Score at Week 12 | -37.59 units on scale | Standard Deviation 22.04 |
| Placebo | Change From Baseline in Patient Global Assessment of Disease Activity Score at Week 12 | -11.58 units on scale | Standard Deviation 22.04 |
p-value: 0.007ANCOVA
Primary
Normalized Net Incremental Area Under the Curve (AUC) for Patient Global Assessment of Disease Activity (PGA) Between Randomization and Week 12
PGA was measured using a 100mm Visual Analog Scale (VAS) ranging from 0=very good to 100=very bad. The normalized net incremental area under the curve of the PGA is the area between the baseline and the PGA curve as a function of time (week 2, 4, 8, 12). AUC was computed using the linear trapezoidal method. All the areas above the baseline and under the curve are positive and all the area below the baseline and above the curve are negative. The net incremental AUC is the sum of these areas. This result is then divided by the study duration of the patients. (negative value = improvement).
Time frame: 12 weeks
Population: All randomized patients who received at least 1 dose of test article. Last observation carried forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etanercept | Normalized Net Incremental Area Under the Curve (AUC) for Patient Global Assessment of Disease Activity (PGA) Between Randomization and Week 12 | -28.54 mm | Standard Deviation 18.01 |
| Placebo | Normalized Net Incremental Area Under the Curve (AUC) for Patient Global Assessment of Disease Activity (PGA) Between Randomization and Week 12 | -11.07 mm | Standard Deviation 18.01 |
Comparison: Comparison of adjusted meansp-value: 0.02995% CI: [-32.93, -2.01]ANCOVA
Secondary
Number of Patients Achieving a 50% Response on the Patient Global Assessment of Disease Activity
A response is defined as at least a 50% improvement (decrease) from baseline in the patient global assessment of disease activity. The patient global assessment of disease activity was measured using a 100mm Visual Analog Scale (VAS) ranging from 0=very good to 100=very bad.
Time frame: 12 weeks
Population: All randomized patients who received at least 1 dose of test article.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept | Number of Patients Achieving a 50% Response on the Patient Global Assessment of Disease Activity | 8 patients |
| Placebo | Number of Patients Achieving a 50% Response on the Patient Global Assessment of Disease Activity | 2 patients |
p-value: 0.0295% CI: [1.44, 69.26]Generalized estimating equations (GEE)