Psoriasis Vulgaris
Conditions
Brief summary
The primary objective is to demonstrate added benefit of brodalumab versus a selected systemic comparator in treatment of moderate to severe plaque psoriasis in Germany in subjects who have not previously received systemic treatment for psoriasis. Fumaric acid esters have been selected as the comparator because it is an established systemic treatment of psoriasis in Germany.
Detailed description
A 24-week, randomised, open-label, active-controlled, parallel group, multi-centre trial with investigator-blinded efficacy assessments
Interventions
BIOLOGICALBrodalumab
Brodalumab is a recombinant fully human monoclonal immunoglobulin IgG2-antibody that binds with high affinity to human interleukin 17 receptor A (IL-17RA). Blocking IL-17RA inhibits IL-17 cytokine-induced responses and results in reduced or normalised inflammation of the skin in subjects with psoriasis.
Fumaric acid esters have been used to treat psoriasis since 1959. Systemic therapy with fumaric acid esters is based on an established dosing scheme with a gradual increase to improve tolerability, especially with regards to gastrointestinal side effects.
Sponsors
LEO Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Criteria for Inclusion: * Men or women ≥18 years of age at the time of screening. * Subjects with chronic plaque type psoriasis diagnosed at least 6 months before randomisation. * Subjects with moderate to severe plaque psoriasis in whom topical therapy is not adequate and who are candidates for systemic therapy, defined at randomisation by PASI 10, affected BSA \>10%, and DLQI \>10. * Subject has no known history of active tuberculosis. * Subject has a negative test for tuberculosis taken at screening (negative Quantiferon test). * Subject and/or subject's designee is/are capable of administering subcutaneous injections. Main Criteria for Exclusion: * Previous or current systemic treatment of plaque psoriasis or known contraindication for systemic therapy. * Previous or current PUVA (psoralens and ultraviolet A) therapy. * Washouts and non-permitted drugs: 1. Have received phototherapy (UVA light therapy without psoralens, UVB light therapy, excimer laser, tanning beds etc. within 4 weeks of baseline, or 2. Have had topical psoriasis treatment within 2 weeks of baseline (exceptions: bland emollients without urea or beta or alpha hydroxy acids) 3. Have received any biologic immune modulating treatments used for indication other than psoriasis within 4 weeks of baseline or within a period of 5 half-lives of the IMP, whichever is longer 4. Have received any other systemic immune modulating treatment (including but not limited to oral retinoids, methotrexate, calcineurin inhibitors, oral or parenteral corticosteroids etc. used for indications other than psoriasis) within 4 weeks of baseline or within a period of 5 half-lives of the IMP, whichever is longer. * Subjects with any of the following laboratory abnormalities at screening: 1. Leukocyte cell count below 3×10\^9/L or lymphocyte count below 0.7×10\^9/L 2. Aspartate aminotransferase (AST) or alanine transferase (ALT) \> 2× ULN (upper level of normal limit) 3. Absolute neutrophil count \< 2×10\^9/L 4. Serum creatinine \> ULN. * History of depressive disorder within the last 2 years including current antidepressive treatment. * Subjects with a history of suicidal behaviour (suicide attempt). * Any suicidal ideation of severity 4 or 5 based on the eC-SSRS questionnaire at screening. * A PHQ-8 score of ≥10 corresponding to moderate to severe depression at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Static Physician's Global Assessment (sPGA) Scale Score of 0 or 1 at Week 24 | Baseline to Week 24 | sPGA is a 6-point scale that represents the average lesion severity on the trunk and limbs. The assessment is based on the condition of the disease at the time of evaluation. Static Physician's Global Assessment is a scale ranging rom 0 (clear skin) to 5 (severe disease). |
| Having Least 75% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 75 Response) From Baseline at Week 24 | Baseline to Week 24 | The PASI score grades the extent and severity of psoriatic involvement for each of four body regions (head and neck, upper extremities, trunk, and lower extremities) using a 7-point scale for extent of involvement in each body region and 5-point scales for severity of each of the clinical signs redness, thickness, and scalliness in each body region. Psoriasis Area and Severity Index is a scale ranging from 0 (no disease) to 72 (maximal disease). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Having Least 90% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 90 Response) From Baseline at Week 24 | Baseline to Week 24 | The PASI score grades the extent and severity of psoriatic involvement for each of four body regions (head and neck, upper extremities, trunk, and lower extremities) using a 7-point scale for extent of involvement in each body region and 5-point scales for severity of each of the clinical signs redness, thickness, and scalliness in each body region. Psoriasis Area and Severity Index is a scale ranging from 0 (no disease) to 72 (maximal disease). |
| Having 100% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 100 Response) From Baseline at Week 24 | Baseline to Week 24 | The PASI score grades the extent and severity of psoriatic involvement for each of four body regions (head and neck, upper extremities, trunk, and lower extremities) using a 7-point scale for extent of involvement in each body region and 5-point scales for severity of each of the clinical signs redness, thickness, and scalliness in each body region. Psoriasis Area and Severity Index is a scale ranging from 0 (no disease) to 72 (maximal disease). |
| Change From Baseline at Week 24 in PASI Score | Baseline to Week 24 | The PASI score grades the extent and severity of psoriatic involvement for each of four body regions (head and neck, upper extremities, trunk, and lower extremities) using a 7-point scale for extent of involvement in each body region and 5-point scales for severity of each of the clinical signs redness, thickness, and scalliness in each body region. Psoriasis Area and Severity Index is a scale ranging from 0 (no disease) to 72 (maximal disease). A negative change in PASI score means that the PASI score was lower at the time of data collection. |
| Percent Change From Baseline in PASI Score at Week 24 | Baseline to Week 24 | The PASI score grades the extent and severity of psoriatic involvement for each of four body regions (head and neck, upper extremities, trunk, and lower extremities) using a 7-point scale for extent of involvement in each body region and 5-point scales for severity of each of the clinical signs redness, thickness, and scalliness in each body region. Psoriasis Area and Severity Index is a scale ranging from 0 (no disease) to 72 (maximal disease). A negative value in the percent change from baseline that the PASI score was lower at the time of data collection. |
| Change From Baseline at Week 24 in Affected Body Surface Area (BSA) | Baseline to Week 24 | The surface area of the participant's hand (palm and fingers) is used as a reference measurement to calculate the percentage of each body region that is affected by psoriasis. One hand is approximately equal to 1% total BSA. Furthermore, the complete body surface area (BSA=100%) can be divided into regions that approximates percentages of BSA as follows: head and neck (10%), upper extremities (20%), the trunk including the axillae and groin (30%), and finally the lower extremities, including the buttocks (40%). A negative value in the percent change from baseline that the affected BSA was lower at the time of data collection. |
| Number of Symptom-free Days From Randomisation to Week 24 | Baseline to Week 24 | The PSI consists of eight psoriasis-specific questions. Trial participants rated the severity of their symptoms in the last 24 hours from 'not at all' to 'very severe,' ranging from 0 to 4. Total scores range from 0 to 32 with higher scores indicating worse symptoms. PSI response is defined as total score ≤8 and no item score \>1. Symptom-free day is defined as having daily total PSI of 0 on that day. |
| Burden of Symptoms | Baseline to Week 24 | Burden of symptoms was assessed as the normalised area under the curve (AUC) of PSI from baseline to the last available assessment. The AUC for the PSI total score was calculated for each participant using the standard trapezoidal rule. The AUC was normalised by dividing it with the time from baseline to the last available assessment of the PSI total score. The PSI consists of eight psoriasis-specific questions. Trial participants rated the severity of their symptoms in the last 24 hours from 'not at all' to 'very severe,' ranging from 0 to 4. Total scores range from 0 to 32 with higher scores indicating worse symptoms. |
| Change From Baseline at Week 24 in Dermatology Life Quality Index (DLQI) Total Score | Baseline to Week 24 | DLQI consists of 10 items addressing the participant's perception of the impact of their skin disease on different aspects of their quality of life over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4 point Likert scale (0 = not at all ⁄not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor QoL. |
| DLQI Total Score of 0 or 1 at Week 24 | Week 24 | DLQI consists of 10 items addressing the participant's perception of the impact of their skin disease on different aspects of their QoL over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4 point Likert scale (0 = not at all ⁄not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor QoL. |
| Psoriasis Symptom Inventory (PSI) Responder at Week 24 (Total Score ≤ 8, With no Item Scores > 1) | Week 24 | The PSI consists of eight psoriasis-specific questions. Trial participants rated the severity of their symptoms in the last 24 hours from 'not at all' to 'very severe,' ranging from 0 to 4. Total scores range from 0 to 32 with higher scores indicating worse symptoms. PSI response is defined as total score ≤8 and no item score \>1. Symptom-free day is defined as having daily total PSI of 0 on that day. |
| PSI Total Score of 0 at Week 24 | Week 24 | The PSI consists of eight psoriasis-specific questions. Trial participants rated the severity of their symptoms in the last 24 hours from 'not at all' to 'very severe,' ranging from 0 to 4. Total scores range from 0 to 32 with higher scores indicating worse symptoms. PSI response is defined as total score ≤8 and no item score \>1. Symptom-free day is defined as having daily total PSI of 0 on that day. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at Week 24 in NAPSI Total Score | Baseline to Week 24 | The Nail Psoriasis Severity Index (NAPSI) grades nails by first dividing the nail area with imaginary horizontal and vertical lines into 4 quarters. The following 8 clinical features of nail psoriasis are then scored based on the number of quarters in which the feature is present (0 to 4) to arrive at a NAPSI score of 0 to 32 for each nail: * Pitting. * Leukonychia. * Red spots in lunula. * Nail plate crumbling. * Oil drop (salmon patch) discoloration. * Onycholysis. * Nail bed hyperkeratosis. * Splinter haemorrhages. A negative change in NAPSI score means that the NAPSI score was lower at the time of data collection. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Brodalumab Subcutaneous (s.c.) brodalumab 210 mg once weekly at Weeks 0, 1, and 2, and 210 mg s.c. every 2 weeks. | 105 |
| Fumaric Acid Esters Oral fumaric acid esters up to 240 mg 3 times daily (TID). | 105 |
| Total | 210 |
Baseline characteristics
| Characteristic | Brodalumab | Fumaric Acid Esters | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 8 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 96 Participants | 97 Participants | 193 Participants |
| Body mass index (BMI) | 28.5 kg/m^2 STANDARD_DEVIATION 5.7 | 28.0 kg/m^2 STANDARD_DEVIATION 6 | 28.2 kg/m^2 STANDARD_DEVIATION 5.9 |
| BSA score | 24.8 score on a scale STANDARD_DEVIATION 15.2 | 25.5 score on a scale STANDARD_DEVIATION 14.9 | 25.2 score on a scale STANDARD_DEVIATION 15.1 |
| DLQI score | 18.8 score on a scale STANDARD_DEVIATION 5.2 | 18.5 score on a scale STANDARD_DEVIATION 4.9 | 18.7 score on a scale STANDARD_DEVIATION 5.1 |
| Duration of psoriasis | 14.3 years STANDARD_DEVIATION 11.5 | 13.2 years STANDARD_DEVIATION 11.7 | 13.7 years STANDARD_DEVIATION 11.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 100 Participants | 103 Participants | 203 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 2 Participants | 7 Participants |
| Height | 175 cm STANDARD_DEVIATION 9.6 | 176 cm STANDARD_DEVIATION 9.8 | 175 cm STANDARD_DEVIATION 9.7 |
| Mean weight in participants weighing <100 kg | 78.4 kg STANDARD_DEVIATION 11.9 | 77.2 kg STANDARD_DEVIATION 12.8 | 77.8 kg STANDARD_DEVIATION 12.4 |
| Mean weight in participants weighing >=100 kg | 116 kg STANDARD_DEVIATION 13.2 | 115 kg STANDARD_DEVIATION 13.9 | 116 kg STANDARD_DEVIATION 13.4 |
| NAPSI score | 6.4 score on a scale STANDARD_DEVIATION 4.4 | 7.7 score on a scale STANDARD_DEVIATION 4.9 | 7.0 score on a scale STANDARD_DEVIATION 4.7 |
| PASI score | 17.2 score on a scale STANDARD_DEVIATION 5.9 | 17.8 score on a scale STANDARD_DEVIATION 6.7 | 17.5 score on a scale STANDARD_DEVIATION 6.3 |
| PSI score | 14.8 score on a scale STANDARD_DEVIATION 5.4 | 17.9 score on a scale STANDARD_DEVIATION 5.3 | 16.3 score on a scale STANDARD_DEVIATION 5.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 104 Participants | 105 Participants | 209 Participants |
| Region of Enrollment Germany | 105 participants | 105 participants | 210 participants |
| Sex: Female, Male Female | 32 Participants | 33 Participants | 65 Participants |
| Sex: Female, Male Male | 73 Participants | 72 Participants | 145 Participants |
| sPGA score | 3.5 score on a scale STANDARD_DEVIATION 0.6 | 3.5 score on a scale STANDARD_DEVIATION 0.7 | 3.5 score on a scale STANDARD_DEVIATION 0.6 |
| Weight | 87.8 kg STANDARD_DEVIATION 20.4 | 86.6 kg STANDARD_DEVIATION 21.1 | 87.2 kg STANDARD_DEVIATION 20.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 104 | 0 / 102 |
| other Total, other adverse events | 66 / 104 | 90 / 102 |
| serious Total, serious adverse events | 3 / 104 | 1 / 102 |
Outcome results
Primary
Having Least 75% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 75 Response) From Baseline at Week 24
The PASI score grades the extent and severity of psoriatic involvement for each of four body regions (head and neck, upper extremities, trunk, and lower extremities) using a 7-point scale for extent of involvement in each body region and 5-point scales for severity of each of the clinical signs redness, thickness, and scalliness in each body region. Psoriasis Area and Severity Index is a scale ranging from 0 (no disease) to 72 (maximal disease).
Time frame: Baseline to Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brodalumab | Having Least 75% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 75 Response) From Baseline at Week 24 | 85 Participants |
| Fumaric Acid Esters | Having Least 75% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 75 Response) From Baseline at Week 24 | 40 Participants |
Comparison: Estimated risk difference, 95% CI and p-value are derived from Cochran-Mantel-Haenszel (CMH) analysis stratified by weight group at baseline (≤100 kg, \> 100 kg). Non-responder Imputation (NRI) was used to impute missing data. Treatment groups were defined as randomised treatment.p-value: <0.00195% CI: [30.93, 54.79]Cochran-Mantel-Haenszel
Primary
Static Physician's Global Assessment (sPGA) Scale Score of 0 or 1 at Week 24
sPGA is a 6-point scale that represents the average lesion severity on the trunk and limbs. The assessment is based on the condition of the disease at the time of evaluation. Static Physician's Global Assessment is a scale ranging rom 0 (clear skin) to 5 (severe disease).
Time frame: Baseline to Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brodalumab | Static Physician's Global Assessment (sPGA) Scale Score of 0 or 1 at Week 24 | 68 Participants |
| Fumaric Acid Esters | Static Physician's Global Assessment (sPGA) Scale Score of 0 or 1 at Week 24 | 21 Participants |
Comparison: Estimated risk difference, 95% CI and p-value are derived from Cochran-Mantel-Haenszel (CMH) analysis stratified by weight group at baseline (≤100 kg, \> 100 kg). Non-responder Imputation (NRI) was used to impute missing data. Treatment groups were defined as randomised treatment.p-value: <0.00195% CI: [32.81, 56.71]Cochran-Mantel-Haenszel
Secondary
Burden of Symptoms
Burden of symptoms was assessed as the normalised area under the curve (AUC) of PSI from baseline to the last available assessment. The AUC for the PSI total score was calculated for each participant using the standard trapezoidal rule. The AUC was normalised by dividing it with the time from baseline to the last available assessment of the PSI total score. The PSI consists of eight psoriasis-specific questions. Trial participants rated the severity of their symptoms in the last 24 hours from 'not at all' to 'very severe,' ranging from 0 to 4. Total scores range from 0 to 32 with higher scores indicating worse symptoms.
Time frame: Baseline to Week 24
Population: Not all participants had recorded PSI data, therefore the analysed number of participants is lower than the randomised number of participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Brodalumab | Burden of Symptoms | 6.00 score on a scale | Standard Error 0.54 |
| Fumaric Acid Esters | Burden of Symptoms | 10.92 score on a scale | Standard Error 0.55 |
Comparison: The AUC was analysed using analysis of covariance (ANCOVA) with treatment group, baseline weight group, and the baseline PSI total score as explanatory variables. Treatment groups are defined as randomised treatment.p-value: <0.00195% CI: [-6.31, -3.53]ANCOVA
Secondary
Change From Baseline at Week 24 in Affected Body Surface Area (BSA)
The surface area of the participant's hand (palm and fingers) is used as a reference measurement to calculate the percentage of each body region that is affected by psoriasis. One hand is approximately equal to 1% total BSA. Furthermore, the complete body surface area (BSA=100%) can be divided into regions that approximates percentages of BSA as follows: head and neck (10%), upper extremities (20%), the trunk including the axillae and groin (30%), and finally the lower extremities, including the buttocks (40%). A negative value in the percent change from baseline that the affected BSA was lower at the time of data collection.
Time frame: Baseline to Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Brodalumab | Change From Baseline at Week 24 in Affected Body Surface Area (BSA) | -20.82 percent change | Standard Error 1.48 |
| Fumaric Acid Esters | Change From Baseline at Week 24 in Affected Body Surface Area (BSA) | -11.91 percent change | Standard Error 1.48 |
Comparison: The endpoint was analysed using mixed model for repeated measures (MMRM) model including treatment group, week, interaction between treatment and time, baseline value, and baseline weight group as fixed factors. Within participant covariance was estimated by an unstructured covariance matrix. Treatment groups were defined as randomised treatment.p-value: <0.00195% CI: [-13, -4.81]Mixed Models Analysis
Secondary
Change From Baseline at Week 24 in Dermatology Life Quality Index (DLQI) Total Score
DLQI consists of 10 items addressing the participant's perception of the impact of their skin disease on different aspects of their quality of life over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4 point Likert scale (0 = not at all ⁄not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor QoL.
Time frame: Baseline to Week 24
Population: The number of analysed participants is not the same as the number of randomised participants, as participants with missing data in all visits for a given endpoint are not included in the mixed model for repeated measurements (MMRM) analysis used to analyse the endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Brodalumab | Change From Baseline at Week 24 in Dermatology Life Quality Index (DLQI) Total Score | -16.67 score on a scale | Standard Error 0.61 |
| Fumaric Acid Esters | Change From Baseline at Week 24 in Dermatology Life Quality Index (DLQI) Total Score | -14.10 score on a scale | Standard Error 0.7 |
Comparison: The endpoint is analysed by using mixed model for repeated measurements (MMRM) model including treatment group, week, interaction between treatment and time, baseline value, and baseline weight group as fixed factors. Within participant covariance was estimated by an unstructured covariance matrix. Treatment groups are defined as randomised treatment.p-value: 0.00495% CI: [-4.32, -0.82]Mixed Models Analysis
Secondary
Change From Baseline at Week 24 in PASI Score
The PASI score grades the extent and severity of psoriatic involvement for each of four body regions (head and neck, upper extremities, trunk, and lower extremities) using a 7-point scale for extent of involvement in each body region and 5-point scales for severity of each of the clinical signs redness, thickness, and scalliness in each body region. Psoriasis Area and Severity Index is a scale ranging from 0 (no disease) to 72 (maximal disease). A negative change in PASI score means that the PASI score was lower at the time of data collection.
Time frame: Baseline to Week 24
Population: The number of analysed participants is not the same as the number of randomised participants, as participants with missing data in all visits for a given endpoint are not included in the mixed model for repeated measurements (MMRM) analysis used to analyse the endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Brodalumab | Change From Baseline at Week 24 in PASI Score | -15.69 score on a scale | Standard Error 0.59 |
| Fumaric Acid Esters | Change From Baseline at Week 24 in PASI Score | -12.62 score on a scale | Standard Error 0.67 |
Comparison: The endpoint was analysed using mixed model for repeated measures (MMRM) model including treatment group, week, interaction between treatment and time, baseline value, and baseline weight group as fixed factors. Within participant covariance was estimated by an unstructured covariance matrix. Treatment groups were defined as randomised treatment.p-value: <0.00195% CI: [-4.83, -1.33]Mixed Models Analysis
Secondary
DLQI Total Score of 0 or 1 at Week 24
DLQI consists of 10 items addressing the participant's perception of the impact of their skin disease on different aspects of their QoL over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4 point Likert scale (0 = not at all ⁄not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor QoL.
Time frame: Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brodalumab | DLQI Total Score of 0 or 1 at Week 24 | 70 Participants |
| Fumaric Acid Esters | DLQI Total Score of 0 or 1 at Week 24 | 27 Participants |
p-value: <0.00195% CI: [28.75, 53.16]Cochran-Mantel-Haenszel
Secondary
Having 100% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 100 Response) From Baseline at Week 24
The PASI score grades the extent and severity of psoriatic involvement for each of four body regions (head and neck, upper extremities, trunk, and lower extremities) using a 7-point scale for extent of involvement in each body region and 5-point scales for severity of each of the clinical signs redness, thickness, and scalliness in each body region. Psoriasis Area and Severity Index is a scale ranging from 0 (no disease) to 72 (maximal disease).
Time frame: Baseline to Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brodalumab | Having 100% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 100 Response) From Baseline at Week 24 | 42 Participants |
| Fumaric Acid Esters | Having 100% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 100 Response) From Baseline at Week 24 | 9 Participants |
Comparison: Estimated risk difference, 95% CI and p-value are derived from Cochran-Mantel-Haenszel (CMH) analysis stratified by weight group at baseline (≤100 kg, \> 100 kg). Non-responder Imputation (NRI) was used to impute missing data. Treatment groups were defined as randomised treatment.p-value: <0.00195% CI: [20.76, 42.1]Cochran-Mantel-Haenszel
Secondary
Having Least 90% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 90 Response) From Baseline at Week 24
The PASI score grades the extent and severity of psoriatic involvement for each of four body regions (head and neck, upper extremities, trunk, and lower extremities) using a 7-point scale for extent of involvement in each body region and 5-point scales for severity of each of the clinical signs redness, thickness, and scalliness in each body region. Psoriasis Area and Severity Index is a scale ranging from 0 (no disease) to 72 (maximal disease).
Time frame: Baseline to Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brodalumab | Having Least 90% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 90 Response) From Baseline at Week 24 | 69 Participants |
| Fumaric Acid Esters | Having Least 90% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 90 Response) From Baseline at Week 24 | 23 Participants |
Comparison: Estimated risk difference, 95% CI and p-value are derived from Cochran-Mantel-Haenszel (CMH) analysis stratified by weight group at baseline (≤100 kg, \> 100 kg). Non-responder Imputation (NRI) was used to impute missing data. Treatment groups were defined as randomised treatment.p-value: <0.00195% CI: [31.78, 55.84]Cochran-Mantel-Haenszel
Secondary
Number of Symptom-free Days From Randomisation to Week 24
The PSI consists of eight psoriasis-specific questions. Trial participants rated the severity of their symptoms in the last 24 hours from 'not at all' to 'very severe,' ranging from 0 to 4. Total scores range from 0 to 32 with higher scores indicating worse symptoms. PSI response is defined as total score ≤8 and no item score \>1. Symptom-free day is defined as having daily total PSI of 0 on that day.
Time frame: Baseline to Week 24
Population: PSI data was missing for many participants at baseline and Week 24. For this reason, no statistical analysis was performed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Brodalumab | Number of Symptom-free Days From Randomisation to Week 24 | 0.44 days | Standard Deviation 0.8 |
| Fumaric Acid Esters | Number of Symptom-free Days From Randomisation to Week 24 | 0.42 days | Standard Deviation 1.3 |
Secondary
Percent Change From Baseline in PASI Score at Week 24
The PASI score grades the extent and severity of psoriatic involvement for each of four body regions (head and neck, upper extremities, trunk, and lower extremities) using a 7-point scale for extent of involvement in each body region and 5-point scales for severity of each of the clinical signs redness, thickness, and scalliness in each body region. Psoriasis Area and Severity Index is a scale ranging from 0 (no disease) to 72 (maximal disease). A negative value in the percent change from baseline that the PASI score was lower at the time of data collection.
Time frame: Baseline to Week 24
Population: The number of analysed participants is not the same as the number of randomised participants, as participants with missing data in all visits for a given endpoint are not included in the mixed model for repeated measurements (MMRM) analysis used to analyse the endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Brodalumab | Percent Change From Baseline in PASI Score at Week 24 | -90.03 percent change in PASI | Standard Error 2.25 |
| Fumaric Acid Esters | Percent Change From Baseline in PASI Score at Week 24 | -73.67 percent change in PASI | Standard Error 2.63 |
Comparison: The endpoint was analysed using mixed model for repeated measures (MMRM) model including treatment group, week, interaction between treatment and time, baseline value, and baseline weight group as fixed factors. Within participant covariance was estimated by an unstructured covariance matrix. Treatment groups were defined as randomised treatment.p-value: <0.00195% CI: [-23.03, -9.68]Mixed Models Analysis
Secondary
PSI Total Score of 0 at Week 24
The PSI consists of eight psoriasis-specific questions. Trial participants rated the severity of their symptoms in the last 24 hours from 'not at all' to 'very severe,' ranging from 0 to 4. Total scores range from 0 to 32 with higher scores indicating worse symptoms. PSI response is defined as total score ≤8 and no item score \>1. Symptom-free day is defined as having daily total PSI of 0 on that day.
Time frame: Week 24
Population: PSI data was missing for many participants at baseline and Week 24. For this reason, no statistical analysis was performed. The data shown is therefore descriptive data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brodalumab | PSI Total Score of 0 at Week 24 | 5 Participants |
| Fumaric Acid Esters | PSI Total Score of 0 at Week 24 | 3 Participants |
Secondary
Psoriasis Symptom Inventory (PSI) Responder at Week 24 (Total Score ≤ 8, With no Item Scores > 1)
The PSI consists of eight psoriasis-specific questions. Trial participants rated the severity of their symptoms in the last 24 hours from 'not at all' to 'very severe,' ranging from 0 to 4. Total scores range from 0 to 32 with higher scores indicating worse symptoms. PSI response is defined as total score ≤8 and no item score \>1. Symptom-free day is defined as having daily total PSI of 0 on that day.
Time frame: Week 24
Population: PSI data was missing for many participants at baseline and Week 24. For this reason, no statistical analysis was performed. The data shown is therefore descriptive data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brodalumab | Psoriasis Symptom Inventory (PSI) Responder at Week 24 (Total Score ≤ 8, With no Item Scores > 1) | 15 Participants |
| Fumaric Acid Esters | Psoriasis Symptom Inventory (PSI) Responder at Week 24 (Total Score ≤ 8, With no Item Scores > 1) | 13 Participants |
Other Pre-specified
Change From Baseline at Week 24 in NAPSI Total Score
The Nail Psoriasis Severity Index (NAPSI) grades nails by first dividing the nail area with imaginary horizontal and vertical lines into 4 quarters. The following 8 clinical features of nail psoriasis are then scored based on the number of quarters in which the feature is present (0 to 4) to arrive at a NAPSI score of 0 to 32 for each nail: * Pitting. * Leukonychia. * Red spots in lunula. * Nail plate crumbling. * Oil drop (salmon patch) discoloration. * Onycholysis. * Nail bed hyperkeratosis. * Splinter haemorrhages. A negative change in NAPSI score means that the NAPSI score was lower at the time of data collection.
Time frame: Baseline to Week 24
Population: Only participants with nail involvement at baseline were included in the analysis. Therefore the number of analysed participants differs from the number of randomised participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Brodalumab | Change From Baseline at Week 24 in NAPSI Total Score | -2.97 score on a scale | Standard Error 0.54 |
| Fumaric Acid Esters | Change From Baseline at Week 24 in NAPSI Total Score | -1.26 score on a scale | Standard Error 0.57 |
p-value: 0.02895% CI: [-3.24, -0.19]Mixed Models Analysis