Psoriasis
Conditions
Brief summary
The two objectives of this study were to evaluate long-term efficacy and safety of adalimumab treatment in participants who had moderate to severe chronic plaque psoriasis and to evaluate the effectiveness of adalimumab retreatment in participants who had therapeutic response to adalimumab and were then withdrawn from adalimumab treatment.
Detailed description
Study M03-658 was a continuation study for participants with moderate to severe psoriasis who had participated in a prior psoriasis adalimumab study. Study M03-658 consisted of three sequential treatment periods. The first period was Period O, in which participants received open-label treatment with adalimumab (40 mg every other week or 40 mg every week) for a minimum of 104 weeks and a maximum of 252 weeks. Period O was the only period of the study until May 2008, when the subsequent periods were added via amendment to the protocol. At that time, participants who had achieved satisfactory therapeutic response (a Physician's Global Assessment \[PGA\] of 0, 1, or 2 \[clear, minimal, or mild\]) were given the opportunity to discontinue from the study or to continue and participate in the subsequent two periods. The second period was Period W, a maximum of 52 weeks, in which participants with a PGA of 2 (mild) or less were withdrawn from adalimumab treatment (i.e., participants received no treatment) until relapse of their psoriasis occurred (defined as a PGA of 3 \[moderate\] or worse). The third period was Period R, a 16-week period in which participants were retreated with open-label adalimumab (80 mg initial dose followed by 40 mg every other week). Period O was designed to evaluate the first objective regarding long-term efficacy and safety of adalimumab treatment, and Period R was designed to evaluate the effectiveness of adalimumab retreatment following relapse. Specific subsets of the study population that were identified as the populations of interest were the modified intent-to-treat populations for Period W and Period R, and these are described further in the outcome measures.
Interventions
DRUGadalimumab
40 mg every other week or 40 mg every week by subcutaneous injection
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
* Subject was age 18 or older and in good health (Investigator discretion) with a recent stable medical history. * Subjects who met the requirements from previous adalimumab psoriasis study participation.
Exclusion criteria
* Subject considered by the Investigator, for any reason, to be an unsuitable candidate for the study. * Female subject who was pregnant or breast-feeding or considering becoming pregnant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Physician's Global Assessment of Clear or Minimal at Week 16 of Period R | Week 16 of Period R | The Physician's Global Assessment \[PGA\] was scored by the physician using a 6-point scale (0-5) for the degree of overall lesion severity, where 0 = clear, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe, and 5 = very severe. Subjects with a PGA of Clear or Minimal overall lesion severity had scores of 0 or 1. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Physician's Global Assessment of Clear or Minimal at Week 120 | Week 120 | The Physician's Global Assessment \[PGA\] was scored by the physician using a 6-point scale (0-5) for the degree of overall lesion severity, where 0 = clear, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe, and 5 = very severe. Subjects with a PGA of Clear or Minimal overall lesion severity had scores of 0 or 1. |
| Percentage of Participants Who Achieved a Psoriasis Area and Severity Index 75 (PASI 75) Response at Week 60 | Week 60 | Psoriasis Area and Severity Index (PASI) scores were calculated from assessments at 4 designated anatomical sites (head, upper extremities, trunk, lower extremities) using both severity and area subscores (i.e., degree of and amount of psoriatic involvement per site). PASI scores range from 0.0 (best) to 72.0 (worst), with the highest score representing complete erythroderma of the severest degree. Positive percent decreases indicate improvement, with the best improvement being 100%. A PASI 75 response was at least a 75% reduction in PASI score from baseline PASI score of the initial study. |
| Percentage of Participants Who Achieved a Psoriasis Area and Severity Index 75 (PASI 75) Response at Week 120 | Week 120 | Psoriasis Area and Severity Index (PASI) scores were calculated from assessments at 4 designated anatomical sites (head, upper extremities, trunk, lower extremities) using both severity and area subscores (i.e., degree of and amount of psoriatic involvement per site). PASI scores range from 0.0 (best) to 72.0 (worst), with the highest score representing complete erythroderma of the severest degree. Positive percent decreases indicate improvement, with the best improvement being 100%. A PASI 75 response was at least a 75% reduction in PASI score from baseline PASI score of the initial study. |
| Percentage of Participants With a Physician's Global Assessment of Clear or Minimal at Week 60 | Week 60 | The Physician's Global Assessment \[PGA\] was scored by the physician using a 6-point scale (0-5) for the degree of overall lesion severity, where 0 = clear, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe, and 5 = very severe. Subjects with a PGA of Clear or Minimal overall lesion severity had scores of 0 or 1. |
| Percentage of Period R Modified Intent-to-Treat Participants Who Relapsed in Period W and Subsequently Had a Physician's Global Assessment of Clear or Minimal at Week 16 of Period R | Week 16 of Period R | The Physician's Global Assessment \[PGA\] was scored by the physician using a 6-point scale (0-5) for the degree of overall lesion severity, where 0 = clear, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe, and 5 = very severe. Subjects with a PGA of Clear or Minimal overall lesion severity had scores of 0 or 1. |
| Percentage of Period R Modified Intent-to-Treat Participants Who Did Not Relapse in Period W and Subsequently Had a Physician's Global Assessment of Clear or Minimal at Week 16 of Period R | Week 16 of Period R | The Physician's Global Assessment \[PGA\] was scored by the physician using a 6-point scale (0-5) for the degree of overall lesion severity, where 0 = clear, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe, and 5 = very severe. Subjects with a PGA of Clear or Minimal overall lesion severity had scores of 0 or 1. |
| Time to Relapse in Period W | Period W | Relapse of psoriasis was defined as a Physician's Global Assessment (assessment of overall lesion severity) score of greater than or equal to 3 (3=moderate; 4=severe; 5=very severe). |
Countries
Austria, Belgium, Canada, France, Germany, Poland, Puerto Rico, Spain, Switzerland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Adalimumab Treatment All participants in the study who received at least one dose of adalimumab. In this study, participants were treated with adalimumab 40 mg every other week (eow) or 40 mg every week by subcutaneous injection (SC) in Period O and then were retreated with open-label adalimumab 40 mg eow SC (after an 80 mg initial dose) in Period R after withdrawal from adalimumab treatment in Period W. | 1,468 |
| Total | 1,468 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Period O - Open-label Treatment | Administrative reasons | 2 |
| Period O - Open-label Treatment | Adverse Event | 82 |
| Period O - Open-label Treatment | Death | 6 |
| Period O - Open-label Treatment | Lack of Efficacy | 198 |
| Period O - Open-label Treatment | Lost to Follow-up | 91 |
| Period O - Open-label Treatment | Other reasons | 68 |
| Period O - Open-label Treatment | Protocol Violation | 12 |
| Period O - Open-label Treatment | Withdrawal by Subject | 147 |
| Period R - Retreatment 16 Weeks | Adverse Event | 4 |
| Period R - Retreatment 16 Weeks | Lack of Efficacy | 5 |
| Period R - Retreatment 16 Weeks | Lost to Follow-up | 11 |
| Period R - Retreatment 16 Weeks | Other reasons | 6 |
| Period R - Retreatment 16 Weeks | Withdrawal by Subject | 9 |
| Period W (Withdrawal) - No Treatment | Administrative reasons | 1 |
| Period W (Withdrawal) - No Treatment | Adverse Event | 4 |
| Period W (Withdrawal) - No Treatment | Death | 2 |
| Period W (Withdrawal) - No Treatment | Lost to Follow-up | 11 |
| Period W (Withdrawal) - No Treatment | Other reasons | 18 |
| Period W (Withdrawal) - No Treatment | Period W Close-out | 129 |
| Period W (Withdrawal) - No Treatment | Relapse (PGA >= 3) | 397 |
| Period W (Withdrawal) - No Treatment | Withdrawal by Subject | 46 |
Baseline characteristics
| Characteristic | All Adalimumab Treatment |
|---|---|
| Age Continuous | 44.1 years STANDARD_DEVIATION 12.75 |
| Region of Enrollment Austria | 34 participants |
| Region of Enrollment Belgium | 15 participants |
| Region of Enrollment Canada | 501 participants |
| Region of Enrollment France | 45 participants |
| Region of Enrollment Germany | 36 participants |
| Region of Enrollment Poland | 12 participants |
| Region of Enrollment Spain | 20 participants |
| Region of Enrollment Switzerland | 3 participants |
| Region of Enrollment United States | 802 participants |
| Sex: Female, Male Female | 470 Participants |
| Sex: Female, Male Male | 998 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1,036 / 1,468 |
| serious Total, serious adverse events | 189 / 1,468 |
Outcome results
Primary
Percentage of Participants With a Physician's Global Assessment of Clear or Minimal at Week 16 of Period R
The Physician's Global Assessment \[PGA\] was scored by the physician using a 6-point scale (0-5) for the degree of overall lesion severity, where 0 = clear, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe, and 5 = very severe. Subjects with a PGA of Clear or Minimal overall lesion severity had scores of 0 or 1.
Time frame: Week 16 of Period R
Population: The Period R Modified Intent-to-Treat population included 178 participants who relapsed and 107 participants who did not relapse in Period W when therapy was withdrawn; all received Period R adalimumab 40 mg every other week (after an 80 mg initial dose). Results were analyzed using non-responder imputation (NRI) for missing values.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period O Adalimumab EOW Treatment Population | Percentage of Participants With a Physician's Global Assessment of Clear or Minimal at Week 16 of Period R | 76.5 percentage of participants |
Other Pre-specified
Percentage of Participants Who Achieved a Psoriasis Area and Severity Index 75 (PASI 75) Response at Week 120
Psoriasis Area and Severity Index (PASI) scores were calculated from assessments at 4 designated anatomical sites (head, upper extremities, trunk, lower extremities) using both severity and area subscores (i.e., degree of and amount of psoriatic involvement per site). PASI scores range from 0.0 (best) to 72.0 (worst), with the highest score representing complete erythroderma of the severest degree. Positive percent decreases indicate improvement, with the best improvement being 100%. A PASI 75 response was at least a 75% reduction in PASI score from baseline PASI score of the initial study.
Time frame: Week 120
Population: A subset of the the All Adalimumab Treatment population who initiated treatment with an adalimumab 40 mg every other week (eow) injection or placebo injection in a prior study. Results were analyzed using Last Observation Carried Forward (LOCF) imputation for missing values.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period O Adalimumab EOW Treatment Population | Percentage of Participants Who Achieved a Psoriasis Area and Severity Index 75 (PASI 75) Response at Week 120 | 57.3 percentage of participants |
Other Pre-specified
Percentage of Participants Who Achieved a Psoriasis Area and Severity Index 75 (PASI 75) Response at Week 60
Psoriasis Area and Severity Index (PASI) scores were calculated from assessments at 4 designated anatomical sites (head, upper extremities, trunk, lower extremities) using both severity and area subscores (i.e., degree of and amount of psoriatic involvement per site). PASI scores range from 0.0 (best) to 72.0 (worst), with the highest score representing complete erythroderma of the severest degree. Positive percent decreases indicate improvement, with the best improvement being 100%. A PASI 75 response was at least a 75% reduction in PASI score from baseline PASI score of the initial study.
Time frame: Week 60
Population: A subset of the All Adalimumab Treatment population who initiated treatment with an adalimumab 40 mg every other week (eow) injection or placebo injection in a prior study. Results were analyzed using Last Observation Carried Forward (LOCF) imputation for missing values.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period O Adalimumab EOW Treatment Population | Percentage of Participants Who Achieved a Psoriasis Area and Severity Index 75 (PASI 75) Response at Week 60 | 61.4 percentage of participants |
Other Pre-specified
Percentage of Participants With a Physician's Global Assessment of Clear or Minimal at Week 120
The Physician's Global Assessment \[PGA\] was scored by the physician using a 6-point scale (0-5) for the degree of overall lesion severity, where 0 = clear, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe, and 5 = very severe. Subjects with a PGA of Clear or Minimal overall lesion severity had scores of 0 or 1.
Time frame: Week 120
Population: A subset of the All Adalimumab Treatment population who initiated treatment with an adalimumab 40 mg every other week (eow) injection or placebo injection in a prior study. Results were analyzed using Last Observation Carried Forward (LOCF) imputation for missing values.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period O Adalimumab EOW Treatment Population | Percentage of Participants With a Physician's Global Assessment of Clear or Minimal at Week 120 | 46.3 percentage of participants |
Other Pre-specified
Percentage of Participants With a Physician's Global Assessment of Clear or Minimal at Week 60
The Physician's Global Assessment \[PGA\] was scored by the physician using a 6-point scale (0-5) for the degree of overall lesion severity, where 0 = clear, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe, and 5 = very severe. Subjects with a PGA of Clear or Minimal overall lesion severity had scores of 0 or 1.
Time frame: Week 60
Population: A subset of the All Adalimumab Treatment population who initiated treatment with an adalimumab 40 mg every other week (eow) injection or placebo injection in a prior study. Results were analyzed using Last Observation Carried Forward (LOCF) imputation for missing values.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period O Adalimumab EOW Treatment Population | Percentage of Participants With a Physician's Global Assessment of Clear or Minimal at Week 60 | 50.6 percentage of participants |
Other Pre-specified
Percentage of Period R Modified Intent-to-Treat Participants Who Did Not Relapse in Period W and Subsequently Had a Physician's Global Assessment of Clear or Minimal at Week 16 of Period R
The Physician's Global Assessment \[PGA\] was scored by the physician using a 6-point scale (0-5) for the degree of overall lesion severity, where 0 = clear, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe, and 5 = very severe. Subjects with a PGA of Clear or Minimal overall lesion severity had scores of 0 or 1.
Time frame: Week 16 of Period R
Population: Participants in the Period R mITT population who did not relapse (did not have a PGA greater than or equal to 3) with adalimumab treatment withdrawal during Period W. Results were analyzed using non-responder imputation (NRI) for missing values.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period O Adalimumab EOW Treatment Population | Percentage of Period R Modified Intent-to-Treat Participants Who Did Not Relapse in Period W and Subsequently Had a Physician's Global Assessment of Clear or Minimal at Week 16 of Period R | 88.8 percentage of participants |
Other Pre-specified
Percentage of Period R Modified Intent-to-Treat Participants Who Relapsed in Period W and Subsequently Had a Physician's Global Assessment of Clear or Minimal at Week 16 of Period R
The Physician's Global Assessment \[PGA\] was scored by the physician using a 6-point scale (0-5) for the degree of overall lesion severity, where 0 = clear, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe, and 5 = very severe. Subjects with a PGA of Clear or Minimal overall lesion severity had scores of 0 or 1.
Time frame: Week 16 of Period R
Population: Participants in the Period R mITT population who had relapsed (had a PGA of greater than or equal to 3) with adalimumab treatment withdrawal during Period W. Results were analyzed using non-responder imputation (NRI) for missing values.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period O Adalimumab EOW Treatment Population | Percentage of Period R Modified Intent-to-Treat Participants Who Relapsed in Period W and Subsequently Had a Physician's Global Assessment of Clear or Minimal at Week 16 of Period R | 69.1 percentage of participants |
Other Pre-specified
Time to Relapse in Period W
Relapse of psoriasis was defined as a Physician's Global Assessment (assessment of overall lesion severity) score of greater than or equal to 3 (3=moderate; 4=severe; 5=very severe).
Time frame: Period W
Population: Participants in the Period W Modified Intent-to-Treat Population who had relapsed (defined by a PGA of greater than or equal to 3) during Period W and had at least one post-baseline PGA assessment in Period W.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Period O Adalimumab EOW Treatment Population | Time to Relapse in Period W | 141 days |