Efficacy and Safety Study of Guselkumab in the Treatment of Participants With Active Psoriatic Arthritis (PsA)

The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90 percentage (%)-100% involvement), and for erythema, induration and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72 (worst condition). PASI 75 response was defined as at least a 75% reduction in PASI relative to Baseline. As planned, results data was analyzed and reported for the specified arms for this outcome measure.

Change from baseline in HAQ-DI score is a measure of the change in the physical function, where a negative change reflects an improvement and a positive change reflects worsening of physical function. HAQ-DI is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0 indicating no difficulty, to 3 indicating inability to perform a task in that area (that is, lower scores are indicative of better functioning). The total HAQ-DI score ranges from 0-24 with lower score indicating better functioning.

ACR 20 response is defined as at least 20 percent (%) improvement from baseline in both swollen joint (66 joints) and tender joint (68 joints) counts and at least 20% improvement from baseline in 3 of following 5 assessments: patient's assessment of pain (visual analog scale [VAS]: 0-100 millimeter [mm]; 0=no pain and 100=worst possible pain), patient's global assessment of disease activity on arthritis (VAS: 0-100 mm, 0=excellent and 100=poor), physician's global assessment of disease activity (VAS: 0-100mm; 0=no arthritis activity and 100 = extremely active arthritis), patient's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas;derived HAQ-DI ranges from 0 indicating no difficulty, to 3 indicating inability to perform a task in that area) and serum C-Reactive Protein (CRP).

ACR 50 response is defined as at least 50 % improvement from baseline in both swollen joint (66 joints) and tender joint (68 joints) counts and at least 50% improvement from baseline in 3 of following 5 assessments: patient's assessment of pain (VAS:0-100 mm; 0=no pain and 100=worst possible pain), patient's global assessment of disease activity on arthritis (VAS:0-100mm; 0=excellent and 100=poor), physician's global assessment of disease activity (VAS: 0-100mm; 0=no arthritis activity and 100 = extremely active arthritis), patient's assessment of physical function measured by HAQ-DI (defined as a 20-question instrument assessing 8 functional areas;derived HAQ-DI ranges from 0 indicating no difficulty, to 3 indicating inability to perform a task in that area) and serum CRP.

Enthesitis was assessed using the Leeds Enthesitis Index (LEI). The LEI was developed to assess enthesitis in participants with psoriatic arthritis (PsA), and evaluates the presence (score of 1) or absence of pain (score of 0) by applying local pressure to Lateral elbow epicondyle, left and right, Medial femoral condyle, left and right, and Achilles tendon insertion, left and right. LEI scores ranging from 0 (0 sites with tenderness) to 6 (worst possible score; 6 sites with tenderness).

Dactylitis is characterized by swelling of the entire finger or toe. The severity of dactylitis is scored on a scale of 0-3, where 0, 1, 2, 3 indicates none, mild, moderate, severe, respectively in each digit of the hands and feet. The range of total dactylitis scores for a participant is 0-60. Higher score indicates more severe dactylitis.

ACR 20, 50, and 70 response is defined as at least 20%, 50%, and 70% improvement from baseline in swollen joint (66 joints) and tender joint (68 joints) counts and at least 20%, 50%, and 70% improvement from baseline in 3 of following 5 assessments: patient's assessment of pain (VAS: 0-100mm, 0=no pain and 100=worst possible pain), patient's global assessment of disease activity on arthritis (VAS: 0-100mm; 0=excellent and 100=poor), physician's global assessment of disease activity (VAS: 0-100mm; 0=no arthritis activity and 100= extremely active arthritis), patient's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas;derived HAQ-DI ranges from 0 indicating no difficulty, to 3 indicating inability to perform a task in that area) and serum C-Reactive Protein (CRP).

ACR 20, ACR 50 and ACR 70 response is defined as at least 20%, 50%, and 70% improvement from baseline in swollen joint (66 joints) and tender joint (68 joints) counts and at least 20%, 50%, and 70% improvement from baseline in 3 of following 5 assessments: patient's assessment of pain (VAS: 0-100mm, 0=no pain and 100=worst possible pain), patient's global assessment of disease activity on arthritis (VAS: 0-100mm; 0=excellent and 100=poor), physician's global assessment of disease activity (VAS; 0-100mm; 0=no arthritis activity and 100 = extremely active arthritis), patient's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas;derived HAQ-DI ranges from 0 indicating no difficulty, to 3 indicating inability to perform a task in that area) and serum C-Reactive Protein (CRP). As planned, results data was analyzed and reported for the specified arms for this outcome measure.

The 7 components of ACR response are: swollen joint counts (0-66), tender joint counts (0-68), patient's assessment of pain (PAIN) (VAS:0-100mm; 0=no pain and 100=worst possible pain), patient's global assessment of disease activity (GDPT) on arthritis (VAS:0-100mm; 0=excellent and 100= poor), physician's global assessment of disease activity (GDEV) (VAS: 0-100mm; 0=no arthritis activity and 100 = extremely active arthritis), patient's assessment of physical function measured by HAQ-DI (20-question instrument assessing 8 functional areas (total score of 0-24 with lower score indicating better functioning);derived HAQ-DI ranges from 0 indicating no difficulty, to 3 indicating inability to perform a task in that area) and serum CRP.

The 7 components of ACR response are: swollen joint counts (0-66), tender joint counts (0-68), patient's assessment of pain (PAIN) (VAS:0-100mm; 0=no pain and 100=worst possible pain), patient's global assessment of disease activity (GDPT) on arthritis (VAS:0-100mm; 0=excellent and 100= poor), physician's global assessment of disease activity (GDEV) (VAS: 0-100mm; 0=no arthritis activity and 100 = extremely active arthritis), patient's assessment of physical function measured by HAQ-DI (20-question instrument assessing 8 functional areas (total score of 0-24 with lower score indicating better functioning);derived HAQ-DI ranges from 0 indicating no difficulty, to 3 indicating inability to perform a task in that area) and serum CRP.

Change from baseline in HAQ-DI score is a measure of the change in the physical function, where a negative change reflects an improvement and a positive change reflects worsening of physical function. HAQ-DI is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0 indicating no difficulty, to 3 indicating inability to perform a task in that area (that is, lower scores are indicative of better functioning). The total HAQ-DI score ranges from 0-24 with lower score indicating better functioning.

Change from baseline in HAQ-DI score is a measure of the change in the physical function, where a negative change reflects an improvement and a positive change reflects worsening of physical function. HAQ-DI is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area (that is, lower scores are indicative of better functioning). The total HAQ-DI score ranges from 0-24 with lower score indicating better functioning.

HAQ-DI response was defined as >= 0.3 improvement from baseline in HAQ-DI score. HAQ-DI is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0 indicating no difficulty, to 3 indicating inability to perform a task in that area (that is, lower scores are indicative of better functioning). The total HAQ-DI score ranges from 0-24 with lower score indicating better functioning.

HAQ-DI response was defined as >= 0.3 improvement from baseline in HAQ-DI score. HAQ-DI is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0 indicating no difficulty, to 3 indicating inability to perform a task in that area (that is, lower scores are indicative of better functioning). The total HAQ-DI score ranges from 0-24 with lower score indicating better functioning. As planned, results data was analyzed and reported for the specified arms for this outcome measure.

Dactylitis is characterized by swelling of the entire finger or toe. The severity of dactylitis is scored on a scale of 0-3, where 0, 1, 2, 3 indicates none, mild, moderate, severe, respectively in each digit of the hands and feet. The range of total dactylitis scores for a participant is 0-60. Higher score indicates more severe dactylitis.

Dactylitis was characterized by swelling of the entire finger or toe. The severity of dactylitis is scored on a scale of 0-3, where 0, 1, 2, 3 indicates none, mild, moderate, severe, respectively in each digit of the hands and feet. The range of total dactylitis scores for a participant is 0-60. Higher score indicates more severe dactylitis. As planned, results data was analyzed and reported for the specified arms for this outcome measure.

Dactylitis is characterized by swelling of the entire finger or toe. The severity of dactylitis is scored on a scale of 0-3, where 0, 1, 2, 3 indicates none, mild, moderate, severe, respectively in each digit of the hands and feet. The range of total dactylitis scores for a participant is 0-60. Participants with dactylitis had dactylitis score >0. Higher score indicates more severe dactylitis.

Dactylitis was characterized by swelling of the entire finger or toe. The severity of dactylitis is scored on a scale of 0-3, where 0, 1, 2, 3 indicates none, mild, moderate, severe, respectively in each digit of the hands and feet. The range of total dactylitis scores for a participant is 0-60. Higher score indicates greater degree of tenderness.

Enthesitis was assessed using the Leeds Enthesitis Index (LEI). The LEI was developed to assess enthesitis in participants with psoriatic arthritis (PsA), and evaluates the presence (score of 1) or absence of pain (score of 0) by applying local pressure to Lateral elbow epicondyle, left and right, Medial femoral condyle, left and right, and Achilles tendon insertion, left and right. LEI scores ranging from 0 (0 sites with tenderness) to 6 (worst possible score; 6 sites with tenderness).

Enthesitis will be assessed using the Leeds Enthesitis Index (LEI). The LEI was developed to assess enthesitis in participants with PsA, and evaluates the presence (score of 1) or absence of pain (score of 0) by applying local pressure to Lateral elbow epicondyle, left and right, Medial femoral condyle, left and right, and Achilles tendon insertion, left and right. LEI scores ranging from 0 (0 sites with tenderness) to 6 (worst possible score; 6 sites with tenderness).

Enthesitis was assessed using the Leeds Enthesitis Index (LEI). The LEI was developed to assess enthesitis in participants with PsA, and evaluates the presence (score of 1) or absence of pain (score of 0) by applying local pressure to Lateral elbow epicondyle, left and right, Medial femoral condyle, left and right, and Achilles tendon insertion, left and right. Participants with enthesitis had LEI score >0. LEI scores ranging from 0 (0 sites with tenderness) to 6 (worst possible score; 6 sites with tenderness).

Enthesitis will be assessed using the Leeds Enthesitis Index (LEI). The LEI was developed to assess enthesitis in participants with PsA, and evaluates the presence (score of 1) or absence of pain (score of 0) by applying local pressure to Lateral elbow epicondyle, left and right, Medial femoral condyle, left and right, and Achilles tendon insertion, left and right. Participants with enthesitis had LEI score >0. LEI scores ranging from 0 (0 sites with tenderness) to 6 (worst possible score; 6 sites with tenderness).

Change from baseline in PASDAS score measures the change in disease activity where a negative value indicates an improvement and a positive value indicates worsening of PsA disease activity. PASDAS is a PsA disease activity score that assesses 4 domains (joints, entheses, dactylitis and quality of life) of PsA. PASDAS is a derived score combining Patient's Global Assessment of Disease Activity (arthritis and psoriasis, on a 100-unit VAS), Physician's Global Assessment of Disease Activity (on a 100-unit VAS), swollen joint count (66 joints), tender joint count (68 joints), CRP (mg/L), enthesitis based on LEI (scaled to a 0-6 range), dactylitis count (scoring each digit from 0-3 and recoding to 0-1, where any score > 0 equaled 1), and the PCS score of the SF-36 health survey. The total score range is 0-10 and the cutoffs for disease activity were 3.2 (low) to 5.4 (high). Negative changes from baseline indicate improvement of overall disease activity.

Change from baseline in PASDAS score measures the change in disease activity where a negative value indicates an improvement and a positive value indicates worsening of PsA disease activity. PASDAS is a PsA disease activity score that assesses 4 domains (joints, entheses, dactylitis and quality of life) of PsA. PASDAS is a derived score combining Patient's Global Assessment of Disease Activity (arthritis and psoriasis, on a 100-unit VAS), Physician's Global Assessment of Disease Activity (on a 100-unit VAS), swollen joint count (66 joints), tender joint count (68 joints), CRP (mg/L), enthesitis based on LEI (scaled to a 0-6 range), dactylitis count (scoring each digit from 0-3 and recoding to 0-1, where any score > 0 equaled 1), and the PCS score of the SF-36 health survey. The total score range is 0-10 and the cutoffs for disease activity were 3.2 (low) to 5.4 (high). Negative changes from baseline indicate improvement of overall disease activity.

Change from baseline in GRACE index score measures the change in disease activity, where a negative change indicates an improvement and a positive change indicates a worsening of PsA disease activity. GRACE index was converted from Arithmetic Mean of the Desirability Function (AMDF). AMDF is calculated by transforming all variables using predefined algorithms and expressing the total score as a mean with a score range of 0 - 1, where 1 indicates a better state than 0. GRACE Index = (1 - AMDF)*10, where GRACE index has a range of 0-10, with higher scores indicate more active disease. As planned, results data was analyzed and reported for the specified arms for this outcome measure.

Change from baseline in GRACE index score measures the change in disease activity, where a negative change indicates an improvement and a positive change indicates a worsening of PsA disease activity. GRACE index was converted from Arithmetic Mean of the Desirability Function (AMDF). AMDF is calculated by transforming all variables using predefined algorithms and expressing the total score as a mean with a score range of 0 - 1, where 1 indicates a better state than 0. GRACE Index = (1 - AMDF)*10, where GRACE index has a range of 0-10, with higher scores indicate more active disease.

The mCPDAI assessed 4 domains (joints, skin, entheses, and dactylitis). The mCPDAI scores were calculated using the following assessments: joints (66 swollen and 68 tender joint counts), HAQ-DI score, PASI, dactylitis, and enthesitis. Within each domain a score (range 0-3) was assigned, where 0= Not involved, 1= Mild, 2= Moderate and 3= Severe. The scores for each domain were then added together to give a final score range of 0 to 12. A higher score indicates more active disease activity. Negative changes from baseline indicate improvement of PsA disease activity.

The mCPDAI assessed 4 domains (joints, skin, entheses, and dactylitis). The mCPDAI scores were calculated using the following assessments: joints (66 swollen and 68 tender joint counts), HAQ-DI score, PASI, dactylitis, and enthesitis. Within each domain a score (range 0-3) was assigned, where 0= Not involved, 1= Mild, 2= Moderate and 3= Severe. The scores for each domain were then added together to give a final score range of 0 to 12. A higher score indicates more active disease activity. Negative changes from baseline indicate improvement of PsA disease activity.

Change from baseline in DAPSA measures the change in disease activity, where a negative change indicates an improvement and a positive change indicates worsening of disease activity. DAPSA score is a the sum of swollen joint count (66 joints), tender joint count (68 joints), CRP (mg/dL), Patient's Assessment of Pain (on a 10-unit VAS;0=no pain, 10=worst possible pain), and Patient's Global Assessment of Disease Activity (arthritis, on a 10-unit VAS; 0 to 100 centimeter [cm] VAS, 0=excellent and 10=poor). Cut-off values for disease activity: 0-4 remission; 5-14 low; 15-28 moderate; >28 high.

Change from baseline in DAPSA measures the change in disease activity, where a negative change indicates an improvement and a positive change indicates worsening of disease activity. DAPSA score is a the sum of swollen joint count (66 joints), tender joint count (68 joints), CRP (mg/dL), Patient's Assessment of Pain (on a 10-unit VAS;0=no pain, 10=worst possible pain), and Patient's Global Assessment of Disease Activity (arthritis, on a 10-unit VAS; 0 to 10cm VAS, 0=excellent and 10=poor). Cut-off values for disease activity: 0-4 remission; 5-14 low; 15-28 moderate; >28 high.

MDA defines a satisfactory state of disease activity that includes 5 domains of PsA (joint symptoms, skin psoriasis, patient's perspective of pain and disease activity on arthritis and psoriasis, physical function and enthesitis). Participants were classified as achieving MDA if they fulfilled 5 of 7 outcome measures: tender joint count <=1; swollen joint count <=1; PASI <=1; patient pain VAS score of <=15 mm; patient global disease activity on arthritis and psoriasis; VAS score of <=20 mm; Health Assessment Questionnaire score <=0.5; and tender entheseal points <=1.

MDA defines a satisfactory state of disease activity that includes 5 domains of PsA (joint symptoms, skin psoriasis, patient's perspective of pain and disease activity on arthritis and psoriasis, physical function and enthesitis). Participants were classified as achieving MDA if they fulfilled 5 of 7 outcome measures: tender joint count <=1; swollen joint count <=1; PASI <=1; patient pain VAS score of <=15 mm; patient global disease activity on arthritis and psoriasis; VAS score of <=20 mm; Health Assessment Questionnaire score <=0.5; and tender entheseal points <=1.

SF-36 is a multi-domain instrument with 36 items to evaluate the health status and quality of life. It included 8 subscales (physical functioning, physical role functioning, bodily pain, general health perception, vitality, social functioning, emotional role functioning, and mental health), which yielded a Physical Component Summary (PCS) with score range 0-100 (higher score-better quality of life) and a Mental Component Summary (MCS) with score range 0-100 (higher score-better quality of life) in addition to subscale scores. The PCS and MCS scores are normalized to a mean of 50 and standard deviations of 10, based upon general US population norms as presented in this outcome measure. A positive change indicates improvement while a negative change indicates worsening of health status and quality of life.

SF-36 is a multi-domain instrument with 36 items to evaluate the health status and quality of life. It included 8 subscales (physical functioning, physical role functioning, bodily pain, general health perception, vitality, social functioning, emotional role functioning, and mental health), which yielded a Physical Component Summary (PCS) with score range 0-100 (higher score-better quality of life) and a Mental Component Summary (MCS) with score range 0-100 (higher score-better quality of life) in addition to subscale scores. The PCS scores are normalized to a mean of 50 and standard deviations of 10, based upon general US population norms as presented in this outcome measure. A positive change indicates improvement while a negative change indicates worsening of health status and quality of life.

SF-36 is a multi-domain instrument with 36 items to evaluate the health status and quality of life. It included 8 subscales (physical functioning, physical role functioning, bodily pain, general health perception, vitality, social functioning, emotional role functioning, and mental health), which yielded a Physical Component Summary (PCS) with score range 0-100 (higher score-better quality of life) and a Mental Component Summary (MCS) with score range 0-100 (higher score-better quality of life) in addition to subscale scores. The MCS scores are normalized to a mean of 50 and standard deviations of 10, based upon general US population norms as presented in this outcome measure. A positive change indicates improvement while a negative change indicates worsening of health status and quality of life.

SF-36 evaluates 8 individual subscales (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health). Each 8 scales scored from 0 to 100 with higher scores= better health. The scores are normalized to a mean of 50 and standard deviations of 10, based upon general US population norms. Higher scores indicate better health. A positive change indicates improvement while a negative change indicates worsening of health status and quality of life.

SF-36 evaluates 8 individual subscales (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health). Each 8 scales scored from 0 to 100 with higher scores= better health. The scores are normalized to a mean of 50 and standard deviations of 10, based upon general US population norms. Higher scores indicate better health. A positive change indicates improvement while a negative change indicates worsening of health status and quality of life.

RAPID3 is a multi-dimensional health assessment questionnaire that was designed for use in routine clinical care. Three core data set for function, pain, and patient global estimate of disease activity were recorded. Each was scored 0-10 and the score ranges from 0 to 30 with higher scores indicating worse condition. A negative change from baseline indicates improvement in condition.

RAPID3 is a multi-dimensional health assessment questionnaire that was designed for use in routine clinical care. Three core data set for function, pain, and patient global estimate of disease activity were recorded. Each was scored 0-10 and the score ranges from 0 to 30 with higher scores indicating worse condition. A negative change from baseline indicates improvement in condition.

The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90 percentage (%)-100% involvement), and for erythema, induration and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72. PASI 50, 75, 90, and 100 responses were defined as at least a 50%, 75%, 90%, and 100% reduction in PASI relative to Baseline respectively. As planned, results data was analyzed and reported for the specified arms for this outcome measure.

The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90 percentage (%)-100% involvement), and for erythema, induration and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72. PASI 50, 75, 90, and 100 responses were defined as at least a 50%, 75%, 90%, and 100% reduction in PASI relative to Baseline respectively.

The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90 percentage (%)-100% involvement), and for erythema, induration and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72. A negative percent change from baseline indicates the percent improvement from baseline in the severity of psoriatic lesions. As planned, results data was analyzed and reported for the specified arms for this outcome measure.

The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90 percentage (%)-100% involvement), and for erythema, induration and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72. A negative percent change from baseline indicates the percent improvement from baseline in the severity of psoriatic lesions.