Efficacy and Safety of Tildrakizumab in Participants With Moderate-to-Severe Chronic Plaque Psoriasis Who Are Non-Responders to Dimethyl Fumarate Therapy

PASI is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and scaling on a scale range from 0 (no symptoms) to 4 (very marked), together with the percentage (%) of the area affected, rated on a scale from 0 (0%) to 6 (90-100%). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 (no psoriasis) to 72 (the most severe disease). PASI 50, 75, 90 response, is defined as having an improvement (reduction) of greater than or equal to (>=) 50%, 75%, 90% and 100% respectively in PASI score compared to the baseline score.

PASI is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and scaling on a scale range from 0 (no symptoms) to 4 (very marked), together with the percentage (%) of the area affected, rated on a scale from 0 (0%) to 6 (90-100%). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 (no psoriasis) to 72 (the most severe disease). Percentage of participants who will achieve an absolute PASI score <= 5, 3 and 1 at Week 8 and Week 16 will be reported.

PASI is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and scaling on a scale range from 0 (no symptoms) to 4 (very marked), together with the percentage (%) of the area affected, rated on a scale from 0 (0%) to 6 (90-100%). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 (no psoriasis) to 72 (the most severe disease).

PASI is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and scaling on a scale range from 0 (no symptoms) to 4 (very marked), together with the percentage (%) of the area affected, rated on a scale from 0 (0%) to 6 (90-100%). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 (no psoriasis) to 72 (the most severe disease). Baseline value is defined as values collected at Week 1 of Part 1 of the study. Change from baseline will be calculated by subtracting post-dose value baseline value.

BSA is a numerical score used to measure the total area of the body affected by psoriasis. The palm method will be applied: the participant's palm, including the five digits is used as a reference (representing approximately 1% of the total body surface area) and is used to repeatedly cover the lesions on the body. The investigator totals the number of palms required and then estimates the percentage (%) in each of the four body regions: head (including scalp) and neck (10%); upper extremities (20%); trunk (30%); and lower extremities (40%).

BSA is a numerical score used to measure the total area of the body affected by psoriasis. The palm method will be applied: the participant's palm, including the five digits is used as a reference (representing approximately 1% of the total body surface area) and is used to repeatedly cover the lesions on the body. The investigator totals the number of palms required and then estimates the percentage (%) in each of the four body regions: head (including scalp) and neck (10%); upper extremities (20%); trunk (30%); and lower extremities (40%). Baseline value is defined as values collected at Week 1 of Part 1 of the study. Change from baseline will be calculated by subtracting post-dose value baseline value.

The PGA score is used to assess the overall severity of the psoriasis lesions at the time of evaluation. Overall lesions will be graded for erythema, induration, and scale based on 6-point scale ranging from 0 (clear) to 5 (severe). The sum of 3 scales will be divided by 3 to obtain final PGA score.

The scPGA score is used to assess the average severity of scalp psoriasis lesions. The scPGA is also 5-point scale ranging from 0 (clear) to 4 (severe), where higher score indicates severe scalp psoriasis lesions. Only in participants with scalp involvement, the scPGA assessment will be performed.

The PPPGA score is used to assess the average severity of psoriasis lesions on hands and/or feet. The PPPGA is a 5-point scale ranging from 0 (clear) to 4 (severe), where higher score indicates severe psoriasis lesions on hands and/or feet. Only in participants with palmar or plantar involvement the PPPGA assessment will be performed.

The PGA score is used to assess the overall severity of the psoriasis lesions at the time of evaluation. Overall lesions will be graded for erythema, induration, and scale based on 6-point scale ranging from 0 (clear) to 5 (severe). The sum of 3 scales will be divided by 3 to obtain final PGA score.

The scPGA score is used to assess the average severity of scalp psoriasis lesions. The scPGA is also 5-point scale ranging from 0 (clear) to 4 (severe), where higher score indicates severe scalp psoriasis lesions. Only in participants with scalp involvement, the scPGA assessment will be performed.

The PPPGA score is used to assess the average severity of severity of psoriasis lesions on hands and/or feet. The PPPGA is a 5-point scale ranging from 0 (clear) to 4 (severe), where higher score indicates severe psoriasis lesions on hands and/or feet. Only in participants with palmar or plantar involvement the PPPGA assessment will be performed.

The PGA score is used to assess the overall severity of the psoriasis lesions at the time of evaluation. Overall lesions will be graded for erythema, induration, and scale based on 6-point scale ranging from 0 (clear) to 5 (severe). The sum of 3 scales will be divided by 3 to obtain final PGA score. Baseline value is defined as values collected at Week 1 of Part 1 of the study. Change from baseline will be calculated by subtracting post-dose value baseline value.

The scPGA score is used to assess the average severity of scalp psoriasis lesions. The scPGA is also 5-point scale ranging from 0 (clear) to 4 (severe), where higher score indicates severe scalp psoriasis lesions. Only in participants with scalp involvement, the scPGA assessment will be performed. Baseline value is defined as values collected at Week 1 of Part 1 of the study. Change from baseline will be calculated by subtracting post-dose value baseline value.

The PPPGA score is used to assess the average severity of psoriasis lesions on hands and/or feet. The PPPGA is a 5-point scale ranging from 0 (clear) to 4 (severe), where higher score indicates severe psoriasis lesions on hands and/or feet. Only in participants with palmar or plantar involvement the PPPGA assessment will be performed. Baseline value is defined as values collected at Week 1 of Part 1 of the study. Change from baseline will be calculated by subtracting post-dose value baseline value.

DLQI is a questionnaire which is to evaluate the impact on participant's quality of life due to psoriasis. It is composed of ten items related to symptoms, feelings, daily activities, leisure, working or studying activities, personal relationships and opinions about dermatological treatment. Each item is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life. The higher the score, the more quality of life is impaired. The DLQI can also be expressed as a percentage of the maximum possible score of 30.

DLQI is a questionnaire which is to evaluate the impact on participant's quality of life due to psoriasis. It is composed of ten items related to symptoms, feelings, daily activities, leisure, working or studying activities, personal relationships and opinions about dermatological treatment. Each item is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life. The higher the score, the more quality of life is impaired. The DLQI can also be expressed as a percentage of the maximum possible score of 30.

DLQI is a questionnaire which is to evaluate the impact on participant's quality of life due to psoriasis. It is composed of ten items related to symptoms, feelings, daily activities, leisure, working or studying activities, personal relationships and opinions about dermatological treatment. Each item is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life. The higher the score, the more quality of life is impaired. The DLQI can also be expressed as a percentage of the maximum possible score of 30. Baseline value is defined as values collected at Week 1 of Part 1 of the study. Change from baseline will be calculated by subtracting post-dose value baseline value.

Skindex is the dermatological instruments to measure dermatology-specific Health-Related Quality of Life (HRQoL). The 16-item Skindex questionnaire is divided into three domains: questions related to the participant's symptoms (1-4), emotions (5-11), and functioning (12-16). Each question asks the participant to quantify how much a specific aspect of their skin condition bothered them in the week prior to administration of the Skindex-16. The questions are answered on a scale from 0 (never bothered) to 6 (always bothered) with a total possible score ranging from 0 (best HRQoL) to 96 (worst HRQoL). Each item is then transformed to a linear scale from 0 to 100.

Skindex is the best dermatological instruments to measure dermatology-specific Health-Related Quality of Life (HRQoL). The 16-item Skindex questionnaire is divided into three domains: questions related to the participant's symptoms (1-4), emotions (5-11), and functioning (12-16). Each question asks the participant to quantify how much a specific aspect of their skin condition bothered them in the week prior to administration of the Skindex-16. The questions are answered on a scale from 0 (never bothered) to 6 (always bothered) with a total possible score ranging from 0 (best HRQoL) to 96 (worst HRQoL). Each item is then transformed to a linear scale from 0 to 100. Baseline value is defined as values collected at Week 1 of Part 1 of the study. Change from baseline will be calculated by subtracting post-dose value baseline value.

The pruritus-VAS is used to assess the pruritus by ticking the scale, which describes pruritus the best. The pruritus-VAS is a single-item continuous scale comprised of a 10 centimeter (cm) [(100 millimeter (mm)] horizontal/vertical line anchored by two verbal descriptors, one for each symptom extreme. For pruritus intensity, the scale is anchored by "no pruritus" (score of 0) and "worst imaginable pruritus" (score of 100 mm).

The pruritus-VAS is used to assess the pruritus by ticking the scale, which describes pruritus the best. The pruritus-VAS is a single-item continuous scale comprised of a 10 centimeter (cm) [(100 millimeter (mm)] horizontal/vertical line anchored by two verbal descriptors, one for each symptom extreme. For pruritus intensity, the scale is anchored by "no pruritus" (score of 0) and "worst imaginable pruritus" (score of 100 mm). Baseline value is defined as values collected at Week 1 of Part 1 of the study. Change from baseline will be calculated by subtracting post-dose value baseline value.

The MOS score questionnaire consists of 12 items leading to 6 subscales or domains: sleep disturbance, sleep adequacy, daytime sleepiness, 'supposed or known' snoring, being awakened by shortness of breath or by a headache, and quantity of sleep. Subscales are standardised to yield scores from 0 to 100, with the exception of sleep quantity. Higher scores on the MOS score reflects more of the attribute indicated by the subscale name.

The MOS score questionnaire consists of 12 items leading to 6 subscales or domains: sleep disturbance, sleep adequacy, daytime sleepiness, 'supposed or known' snoring, being awakened by shortness of breath or by a headache, and quantity of sleep. Subscales are standardised to yield scores from 0 to 100, with the exception of sleep quantity. Higher scores on the MOS score reflects more of the attribute indicated by the subscale name. Baseline value is defined as values collected at Week 1 of Part 1 of the study. Change from baseline will be calculated by subtracting post-dose value baseline value.

PASI is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and scaling on a scale range from 0 (no symptoms) to 4 (very marked), together with the percentage (%) of the area affected, rated on a scale from 0 (0%) to 6 (90-100%). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 (no psoriasis) to 72 (the most severe disease). Baseline value is defined as values collected at Week 1 of Part 1 of the study.

PGA is used to assess the overall severity of the psoriasis lesions at the time of evaluation. Overall lesions will be graded for erythema, induration, and scale based on 6-point scale ranging from 0 (clear) to 5 (severe). The sum of 3 scales will be divided by 3 to obtain final PGA score. Baseline value is defined as values collected at Week 1 of Part 1 of the study.

The scPGA scores is used to assess the average severity of scalp psoriasis lesions. The scPGA is also 5-point scale ranging from 0 (clear) to 4 (severe), where higher score indicates severe scalp psoriasis lesions. Only in participants with scalp involvement, the scPGA assessment will be performed. Baseline value is defined as values collected at Week 1 of Part 1 of the study.

PPPGA Scores is used to assess the average severity of psoriasis lesions on hands and/or feet. The PPPGA is a 5-point scale ranging from 0 (clear) to 4 (severe), where higher score indicates severe psoriasis lesions on hands and/or feet. Only in participants with palmar or plantar involvement the PPPGA assessment will be performed. Baseline value is defined as values collected at Week 1 of Part 1 of the study.

DLQI is a questionnaire which is to evaluate the impact on participant's quality of life due to psoriasis. It is composed of ten items related to symptoms, feelings, daily activities, leisure, working or studying activities, personal relationships and opinions about dermatological treatment. Each item is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life. The higher the score, the more quality of life is impaired. The DLQI can also be expressed as a percentage of the maximum possible score of 30. Baseline value is defined as values collected at Week 1 of Part 1 of the study.

Skindex is the dermatological instruments to measure dermatology-specific Health-Related Quality of Life (HRQoL). The 16-item Skindex questionnaire is divided into three domains: questions related to the participant's symptoms (1-4), emotions (5-11), and functioning (12-16). Each question asks the participant to quantify how much a specific aspect of their skin condition bothered them in the week prior to administration of the Skindex-16. The questions are answered on a scale from 0 (never bothered) to 6 (always bothered) with a total possible score ranging from 0 (best HRQoL) to 96 (worst HRQoL). Each item is then transformed to a linear scale from 0 to 100. Baseline value is defined as values collected at Week 1 of Part 1 of the study.

The pruritus-VAS is used to assess the pruritus by ticking the scale, which describes pruritus the best. The pruritus-VAS is a single-item continuous scale comprised of a 10 centimeter (cm) [(100 millimeter (mm)] horizontal/vertical line anchored by two verbal descriptors, one for each symptom extreme. For pruritus intensity, the scale is anchored by "no pruritus" (score of 0) and "worst imaginable pruritus" (score of 100 mm). Baseline value is defined as values collected at Week 1 of Part 1 of the study.

The MOS score questionnaire consists of 12 items leading to 6 subscales or domains: sleep disturbance, sleep adequacy, daytime sleepiness, 'supposed or known' snoring, being awakened by shortness of breath or by a headache, and quantity of sleep. Subscales are standardised to yield scores from 0 to 100, with the exception of sleep quantity. Higher scores on the MOS score reflects more of the attribute indicated by the subscale name. Baseline value is defined as values collected at Week 1 of Part 1 of the study.

An Adverse event (AE) is defined as "any untoward medical occurrence in a clinical trial participant (regardless of the administration of the study drug and its causal relationship to it). An AE can therefore be any unfavourable and unintended medical occurrence during the participant's participation in the trial, including deterioration of a pre-existing medical condition, an abnormal clinically significant finding in a laboratory assessment, or an abnormal clinically significant finding in the physical examination or vital sign. Any AE occurring following the start of treatment or occurring before treatment but increasing in severity afterward will be counted as TEAE.