Psoriasis
Conditions
Keywords
Psoriasis, Discontinuation of efalizumab, Managing inflammatory recurrence
Brief summary
This is a pilot investigational study of the appropriate therapeutic regimens to treat subjects experiencing inflammatory recurrence (rebound) of psoriatic disease upon discontinuation of efalizumab therapy and of the biological mechanisms involved in inflammatory disease recurrence and control.
Interventions
DRUGCyclosporins
Starting dose 4.0 - 5.1 mg/kg/day until clinical improvement. Upon clinical improvement, cyclosporin dose to be tapered by 50% every two weeks.
DRUGRetinoids
Starting dose 25 - 50 mg/day until clinical improvement. Upon clinical improvement, retinoid dose to be reduced by 50%. Thereafter, treatment to be continued for 8 weeks and then stopped.
Starting dose 0.25 - 0.5 mg/kg/day until clinical improvement. Upon clinical improvement, corticosteroid dose to be reduced by 50%. Thereafter, corticosteroids to be weaned by 50% every 2 weeks.
DRUGMethotrexate
Starting dose 20 - 25 mg per week until clinical improvement. Upon clinical improvement, dose to be reduced by 25%. Thereafter, methotrexate dose to be reduced by 25% every two weeks.
DRUGSystemic corticosteroids/methotrexate
Upon clinical improvement, corticosteroid dose to be reduced by 50%. Thereafter, to be weaned by 50% every 2 weeks. Methotrexate starting dose 20 - 25 mg per week until clinical improvement. Upon clinical improvement, dose to be reduced by 25%. Thereafter, to be reduced by 25% every two weeks.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Participation in Genentech study ACD2601g, Genentech study HUPA 600 or Serono study IMP24011. * Inflammatory psoriasis disease recurrence occurring up to 2 months after discontinuation of efalizumab that required immediate therapeutic control in the opinion of the Investigator. Psoriasis had to be rapidly developing, symptomatic and inflammatory in nature. * Written informed consent, given prior to any study-related procedure not part of the subject's normal medical care, with the understanding that the subject could withdraw consent at any time without prejudice to his or her future medical care. * Female subjects had to be neither pregnant nor breast-feeding, and had to lack childbearing potential, as defined by either: * Being post-menopausal or surgically sterile, or * Using an accepted form of contraception. * Confirmation that the subject was not pregnant had to be established by a negative urinary hCG test at SD1. A pregnancy test was not required if the subject was post-menopausal or surgically sterile. * Outpatient status at the time of enrolment.
Exclusion criteria
* Disease recurrence that was part of the natural disease progression, was not inflammatory in nature, and was not related to efalizumab study medication in the previous study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Physician's Global Assessment (PGA) of Change Over Time (Good or Better) | 12 weeks | The PGA response was classified according to the following categories by changes in all clinical signs and symptoms as compared to baseline: Cleared: Remission except for residual manifestations such as mild erythema (100% improvement) Excellent: Improvement of 75%-99% except for residual manifestations such as mild erythema Good: Improvement of 50%-74% |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient's Global Psoriasis Assessment (PGPA) | 12 weeks | The PGPA consisted of a single self-explanatory item: On a scale from 0 to 10, with 0 being no psoriasis and 10 the worst psoriasis that you can imagine, please rate the state of your psoriasis right now. Note: Consider only your skin condition and do not consider other aspects that may be related to your psoriasis (such as psoriatic arthritis). |
Participant flow
Recruitment details
Study Initiation Date: 24 February 2004 (first patient, first visit) Study Completion Date: 21 December 2004 (last patient, last visit) Study Centres: 9 clinical centres in Canada
Pre-assignment details
Subjects who satisfied the study's entry criteria were assigned to receive one of five treatment regimens involving accepted therapies for moderate to severe psoriasis
Participants by arm
| Arm | Count |
|---|---|
| Cyclosporin Starting dose 4.0 - 5.1 mg/kg/day until clinical improvement. Upon clinical improvement, cyclosporin dose to be tapered by 50% every two weeks. | 10 |
| Retinoids Starting dose 25 - 50 mg/day until clinical improvement. Upon clinical improvement, retinoid dose to be reduced by 50%. Thereafter, treatment to be continued for 8 weeks and then stopped. | 1 |
| Systemic Corticosteroids Starting dose 0.25 - 0.5 mg/kg/day until clinical improvement. Upon clinical improvement, corticosteroid dose to be reduced by 50%. Thereafter, corticosteroids to be weaned by 50% every 2 weeks. | 8 |
| Methotrexate Starting dose 20 - 25 mg per week until clinical improvement. Upon clinical improvement, dose to be reduced by 25%. Thereafter, methotrexate dose to be reduced by 25% every two weeks. | 20 |
| Systemic Corticosteroids/Methotrexate Corticosteroid starting dose 0.25 - 0.5 mg/kg/day until clinical improvement. Upon clinical improvement, corticosteroid dose to be reduced by 50%.
Thereafter, to be weaned by 50% every 2 weeks. Methotrexate starting dose 20 - 25 mg per week until clinical improvement. Upon clinical improvement, dose to be reduced by 25%. Thereafter, to be reduced by 25% every two weeks. | 2 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Lack of Efficacy | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Cyclosporin | Retinoids | Systemic Corticosteroids | Methotrexate | Systemic Corticosteroids/Methotrexate | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 43 years STANDARD_DEVIATION 12 | 41 years | 44 years STANDARD_DEVIATION 11 | 49 years STANDARD_DEVIATION 10 | 47 years STANDARD_DEVIATION 3 | 46 years STANDARD_DEVIATION 11 |
| Region of Enrollment Canada | 10 participants | 1 participants | 8 participants | 20 participants | 2 participants | 41 participants |
| Sex: Female, Male Female | 5 Participants | 0 Participants | 3 Participants | 7 Participants | 1 Participants | 16 Participants |
| Sex: Female, Male Male | 5 Participants | 1 Participants | 5 Participants | 13 Participants | 1 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 10 | 0 / 1 | 4 / 8 | 11 / 20 | 0 / 2 |
| serious Total, serious adverse events | 0 / 10 | 0 / 1 | 0 / 8 | 0 / 20 | 0 / 2 |
Outcome results
Primary
Physician's Global Assessment (PGA) of Change Over Time (Good or Better)
The PGA response was classified according to the following categories by changes in all clinical signs and symptoms as compared to baseline: Cleared: Remission except for residual manifestations such as mild erythema (100% improvement) Excellent: Improvement of 75%-99% except for residual manifestations such as mild erythema Good: Improvement of 50%-74%
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cyclosporin | Physician's Global Assessment (PGA) of Change Over Time (Good or Better) | 7 participants |
| Retinoids | Physician's Global Assessment (PGA) of Change Over Time (Good or Better) | 0 participants |
| Systemic Corticosteroids | Physician's Global Assessment (PGA) of Change Over Time (Good or Better) | 2 participants |
| Methotrexate | Physician's Global Assessment (PGA) of Change Over Time (Good or Better) | 9 participants |
| Systemic Corticosteroids/Methotrexate | Physician's Global Assessment (PGA) of Change Over Time (Good or Better) | 0 participants |
Secondary
Patient's Global Psoriasis Assessment (PGPA)
The PGPA consisted of a single self-explanatory item: On a scale from 0 to 10, with 0 being no psoriasis and 10 the worst psoriasis that you can imagine, please rate the state of your psoriasis right now. Note: Consider only your skin condition and do not consider other aspects that may be related to your psoriasis (such as psoriatic arthritis).
Time frame: 12 weeks
Population: One patient withdrew
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cyclosporin | Patient's Global Psoriasis Assessment (PGPA) | 5.1 PGPA score | Standard Deviation 2.4 |
| Retinoids | Patient's Global Psoriasis Assessment (PGPA) | 4.0 PGPA score | — |
| Systemic Corticosteroids | Patient's Global Psoriasis Assessment (PGPA) | 5.5 PGPA score | Standard Deviation 2.8 |
| Methotrexate | Patient's Global Psoriasis Assessment (PGPA) | 4.8 PGPA score | Standard Deviation 2.7 |
| Systemic Corticosteroids/Methotrexate | Patient's Global Psoriasis Assessment (PGPA) | 4.5 PGPA score | Standard Deviation 0.7 |