Etanercept and Methotrexate in Combination or as Monotherapy in Psoriatic Arthritis

A positive ACR20 response is defined if the following 3 criteria for improvement from baseline were met:

• ≥ 20% improvement in 68 tender joint count;
• ≥ 20% improvement in 66 swollen joint count; and
• ≥ 20% improvement in at least 3 of the 5 following parameters:

• Patient's assessment of joint pain (measured on a 100 mm visual analog scale [VAS]);
• Patient's global assessment of disease activity (measured on a 100 mm VAS);
• Physician's global assessment of disease activity (measured on a 100 mm VAS);
• Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
• C-reactive protein concentration.

Minimal Disease Activity (MDA) is a measure of low disease activity specific for psoriatic arthritis (PsA) that incorporates measures of joint and entheseal inflammation, skin disease, patient reported outcomes and functional disability to assess disease activity. Participants were classified as achieving MDA if they fulfilled 5 of the following 7 outcome measures:

• Tender joint count (0-68) ≤ 1
• Swollen joint count (0-66) ≤ 1
• Body surface area (BSA) involvement with psoriasis (0% to 100%) ≤ 3%
• Patient global assessment of joint pain VAS (0-100) ≤ 15
• Patient global assessment of disease activity VAS (0-100) ≤ 20
• HAQ-DI (0-3) ≤ 0.5
• Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis index (18 sites assessed for enthesitis with an overall score of 0 - 16) ≤ 1

A positive ACR20 response is defined if the following 3 criteria for improvement from baseline were met:

• ≥ 20% improvement in 68 tender joint count;
• ≥ 20% improvement in 66 swollen joint count; and
• ≥ 20% improvement in at least 3 of the 5 following parameters:

• Patient's assessment of joint pain (measured on a 100 mm visual analog scale [VAS]);
• Patient's global assessment of disease activity (measured on a 100 mm VAS);
• Physician's global assessment of disease activity (measured on a 100 mm VAS);
• Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
• C-reactive protein.

A positive ACR50 response is defined if the following 3 criteria for improvement from baseline were met:

• ≥ 50% improvement in 68 tender joint count;
• ≥ 50% improvement in 66 swollen joint count; and
• ≥ 50% improvement in at least 3 of the 5 following parameters:

• Patient's assessment of joint pain (measured on a 100 mm visual analog scale [VAS]);
• Patient's global assessment of disease activity (measured on a 100 mm VAS);
• Physician's global assessment of disease activity (measured on a 100 mm VAS);
• Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
• C-reactive protein.

A positive ACR70 response is defined if the following 3 criteria for improvement from baseline were met:

• ≥ 70% improvement in 68 tender joint count;
• ≥ 70% improvement in 66 swollen joint count; and
• ≥ 70% improvement in at least 3 of the 5 following parameters:

• Patient's assessment of joint pain (measured on a 100 mm visual analog scale [VAS]);
• Patient's global assessment of disease activity (measured on a 100 mm VAS);
• Physician's global assessment of disease activity (measured on a 100 mm VAS);
• Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
• C-reactive protein.

The tender joint count is an assessment of the pain and/or tenderness of 68 joints using a 0 to 1 point scale (0 = none, 1 = present). The total tender joint count is calculated by summing the number of joints with present tenderness.

The swollen joint count is an assessment of the swelling of 66 joints using a 0 to 1 point scale (0 = none, 1 = present). The total swollen joint count is calculated by summing the number of joints with present swelling.

A global assessment of the participant's arthritis assessed by the physician on a 100 mm visual analog scale (VAS) where 0 mm = No activity at all and 100 mm = Worst activity imaginable.

A global assessment of the participant's arthritis, assessed by the participant on a 100 mm VAS where 0 mm = No arthritis activity at all and 100 mm = Worst arthritis activity imaginable.

A global assessment of the severity of the participant's joint pain, assessed by the participant on a 100 mm VAS where 0 mm = No pain at all and 100 mm = Worst pain imaginable.

The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

C-reactive protein (CRP) is a specific measure of inflammatory activity.

Minimal Disease Activity (MDA) is a measure of low disease activity specific for psoriatic arthritis (PsA) that incorporates measures of joint and entheseal inflammation, skin disease, patient reported outcomes and functional disability to assess disease activity. Participants were classified as achieving MDA if they fulfilled 5 of the following 7 outcome measures:

• Tender joint count (0-68) ≤ 1
• Swollen joint count (0-66) ≤ 1
• Body surface area (BSA) involvement with psoriasis (0% to 100%) ≤ 3%
• Patient global assessment of joint pain VAS (0-100) ≤ 15
• Patient global assessment of disease activity VAS (0-100) ≤ 20
• HAQ-DI (0-3) ≤ 0.5
• Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis index (18 sites assessed for enthesitis with an overall score of 0 - 16) ≤ 1

PASDAS is a measure of disease activity derived from the following variables:

• Physician and patient global assessment of disease activity (assessed on a 0-100 VAS)
• 68 tender joint count
• 66 swollen joint count
• Short Form-36 Questionnaire (SF-36) physical component summary (general health status on a scale from 0-100)
• Tender dactylitis count (each digit assessed for tender dactylitis; total score 0-20)
• Leeds enthesitis index (enthesitis assessed at 6 sites; total score of 0-6)
• CRP level (mg/L)

The composite score is a weighted index where higher scores indicate more severe disease.

The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the following items:

• 28 tender joint count,
• 28 swollen joint count,
• Patient's Global Assessment of Disease Activity measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest;
• Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest.

The CDAI score ranges from 0-76 where lower scores indicate less disease activity.

The Simplified Disease Activity Index (SDAI) is a composite index that is calculated as the sum of the following items:

• 28 tender joint count,
• 28 swollen joint count,
• Patient's Global Assessment of Disease Activity measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest;
• Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest.
• CRP

The SDAI score ranges from 0 to 86 with higher scores representing worse disease.

The DAS28 measures the severity of disease at a specific time and is derived from the following variables:

• 28 tender joint count
• 28 swollen joint count
• C-reactive protein (CRP)
• Patient's global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.

DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.

The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring in 8 functional areas: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains. Two summary component scores are calculated: mental component summary score (MCS) and physical component summary score (PCS). The MCS consists of social functioning, vitality, mental health, and role-emotional scales and the PCS consists of physical functioning, bodily pain, role-physical, and general health scales. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale with higher scores indicating better health status or functioning.

The modified NAPSI scale is a grading system for nail psoriasis that incorporates the following 7 clinical features:

• pitting (scores 0-3, depending on the number of pits)
• nail plate crumbling (scores 0-3, depending on the % of nail involvement)
• onycholysis and oil drop dyschromia (scores 0-3, depending on the % of nail involvement)
• leukonychia (0 = absent, 1 = present)
• red spots in lunula (0 = absent, 1 = present)
• nail bed hyperkeratosis (0 = absent, 1 = present)
• splinter hemorrhages (0 = absent, 1 = present)

In participants with fingernails involved with psoriasis, each fingernail was scored at baseline to determine the worst fingernail (ie, the fingernail with the highest mNAPSI score). This fingernail was followed for the remainder of the study.

mNAPSI scores range from 0-13 where higher scores represent worse nail disease.

The modified NAPSI scale is a grading system for nail psoriasis that incorporates the following 7 clinical features:

• pitting (scores 0-3, depending on the number of pits)
• nail plate crumbling (scores 0-3, depending on the % of nail involvement)
• onycholysis and oil drop dyschromia (scores 0-3, depending on the % of nail involvement)
• leukonychia (0 = absent, 1 = present)
• red spots in lunula (0 = absent, 1 = present)
• nail bed hyperkeratosis (0 = absent, 1 = present)
• splinter hemorrhages (0 = absent, 1 = present)

In participants with fingernails involved with psoriasis, each fingernail was scored at baseline to determine the worst fingernail (ie, the fingernail with the highest mNAPSI score). This fingernail was followed for the remainder of the study.

mNAPSI scores range from 0-13 where higher scores represent worse nail disease. Clear mNAPSI is defined as a score = 0.

The Leeds dactylitis index quantitatively measures dactylitis using the circumference of involved digits and control digits and tenderness of involved digits. Digits affected by dactylitis are defined as those with a 10% difference in the ratio of circumference of the affected digit to the contralateral digit. The control digit is either the contralateral digit (digit on opposite hand or foot), or if the contralateral digit is also affected, values from a standard reference table. Tenderness of affected digits is assessed on a scale from 0 [none] to 3 [worst]. The ratio of circumference between an affected digit and the control digit is multiplied by the tenderness score for the affected digit. The results from each involved digit are summed to provide the final LDI. A higher LDI indicates worse dactylitis.

The Leeds dactylitis index quantitatively measures dactylitis using the circumference of involved digits and control digits and tenderness of involved digits. Digits affected by dactylitis are defined as those with a 10% difference in the ratio of circumference of the affected digit to the contralateral digit. The control digit is either the contralateral digit (digit on opposite hand or foot), or if the contralateral digit is also affected, values from a standard reference table. Tenderness of affected digits is assessed on a scale from 0 [none] to 3 [worst]. The ratio of circumference between an affected digit and the control digit is multiplied by the tenderness score for the affected digit. The results from each involved digit are summed to provide the final LDI. A higher LDI indicates worse dactylitis.

Clear LDI is defined as a score = 0.

The SPARCC enthesitis index assesses enthesitis at 18 sites for palpitation with a resultant total score of 0 to 16 (for scoring purposes, the inferior patella and tibial tuberosity are considered 1 site because of their anatomical proximity). Tenderness at each site is quantified on a dichotomous basis (0 = non-tender, 1 = tender). Entheses assessed are medial epicondyle (left and right), lateral epicondyle (left and right), supraspinatus insertion into greater tuberosity of humerus (left and right), greater trochanter (left and right), quadriceps insertion into superior border of patella (left and right), patellar ligament insertion into inferior pole of patella or tibial tubercle (left and right), Achilles tendon insertion into calcaneum (left and right), plantar fascia insertion into calcaneum (left and right). A higher count represents greater enthesitis burden.

The SPARCC enthesitis index assesses enthesitis at 18 sites for palpitation with a resultant total score of 0 to 16 (for scoring purposes, the inferior patella and tibial tuberosity are considered 1 site because of their anatomical proximity). Tenderness at each site is quantified on a dichotomous basis (0 = non-tender, 1 = tender). Entheses assessed are medial epicondyle (left and right), lateral epicondyle (left and right), supraspinatus insertion into greater tuberosity of humerus (left and right), greater trochanter (left and right), quadriceps insertion into superior border of patella (left and right), patellar ligament insertion into inferior pole of patella or tibial tubercle (left and right), Achilles tendon insertion into calcaneum (left and right), plantar fascia insertion into calcaneum (left and right). A higher count represents greater enthesitis burden.

Clear SPARCC enthesitis is defined as a score = 0.

The physician's assessment of the percentage of the participant's total body surface area involved with psoriasis.

Percent improvement from baseline = (Baseline Value - Post-baseline Value) / Baseline * 100

The physician's assessment of the percentage of the participant's total body surface area involved with psoriasis.

Percent improvement from baseline = (Baseline Value - Post-baseline Value) / Baseline * 100

The static Physician Global Assessment of psoriasis (sPGA) evaluates the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA is assessed on a scale from 0 to 5:

0 = clear (no evidence of plaque elevation, erythema or scaling)

• = almost clear (minimal plaque elevation, erythema or scaling)
• = mild (mild plaque elevation or scaling, light red coloration)
• = moderate (moderate plaque elevation, scaling, light red coloration)
• = marked (marked plaque elevation, thick, non-tenacious scale predominates, bright red coloration)
• = severe (severe plaque elevation, very thick tenacious scaling, dusky to deep red coloration).

The static Physician Global Assessment of psoriasis (sPGA) evaluates the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA is assessed on a scale from 0 to 5:

0 = clear (no evidence of plaque elevation, erythema or scaling)

• = almost clear (minimal plaque elevation, erythema or scaling)
• = mild (mild plaque elevation or scaling, light red coloration)
• = moderate (moderate plaque elevation, scaling, light red coloration)
• = marked (marked plaque elevation, thick, non-tenacious scale predominates, bright red coloration)
• = severe (severe plaque elevation, very thick tenacious scaling, dusky to deep red coloration).

The static Physician Global Assessment of psoriasis (sPGA) evaluates the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA is assessed on a scale from 0 to 5:

0 = clear (no evidence of plaque elevation, erythema or scaling)

• = almost clear (minimal plaque elevation, erythema or scaling)
• = mild (mild plaque elevation or scaling, light red coloration)
• = moderate (moderate plaque elevation, scaling, light red coloration)
• = marked (marked plaque elevation, thick, non-tenacious scale predominates, bright red coloration)
• = severe (severe plaque elevation, very thick tenacious scaling, dusky to deep red coloration).

The static Physician Global Assessment of psoriasis (sPGA) evaluates the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA is assessed on a scale from 0 to 5:

0 = clear (no evidence of plaque elevation, erythema or scaling)

• = almost clear (minimal plaque elevation, erythema or scaling)
• = mild (mild plaque elevation or scaling, light red coloration)
• = moderate (moderate plaque elevation, scaling, light red coloration)
• = marked (marked plaque elevation, thick, non-tenacious scale predominates, bright red coloration)
• = severe (severe plaque elevation, very thick tenacious scaling, dusky to deep red coloration).

The static Physician Global Assessment of psoriasis (sPGA) evaluates the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA is assessed on a scale from 0 to 5:

0 = clear (no evidence of plaque elevation, erythema or scaling)

• = almost clear (minimal plaque elevation, erythema or scaling)
• = mild (mild plaque elevation or scaling, light red coloration)
• = moderate (moderate plaque elevation, scaling, light red coloration)
• = marked (marked plaque elevation, thick, non-tenacious scale predominates, bright red coloration)
• = severe (severe plaque elevation, very thick tenacious scaling, dusky to deep red coloration).

The static Physician Global Assessment of psoriasis (sPGA) evaluates the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA is assessed on a scale from 0 to 5:

0 = clear (no evidence of plaque elevation, erythema or scaling)

• = almost clear (minimal plaque elevation, erythema or scaling)
• = mild (mild plaque elevation or scaling, light red coloration)
• = moderate (moderate plaque elevation, scaling, light red coloration)
• = marked (marked plaque elevation, thick, non-tenacious scale predominates, bright red coloration)
• = severe (severe plaque elevation, very thick tenacious scaling, dusky to deep red coloration).

The static Physician Global Assessment of psoriasis (sPGA) evaluates the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA is assessed on a scale from 0 to 5:

0 = clear (no evidence of plaque elevation, erythema or scaling)

• = almost clear (minimal plaque elevation, erythema or scaling)
• = mild (mild plaque elevation or scaling, light red coloration)
• = moderate (moderate plaque elevation, scaling, light red coloration)
• = marked (marked plaque elevation, thick, non-tenacious scale predominates, bright red coloration)
• = severe (severe plaque elevation, very thick tenacious scaling, dusky to deep red coloration).

The static Physician Global Assessment of psoriasis (sPGA) evaluates the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA is assessed on a scale from 0 to 5:

0 = clear (no evidence of plaque elevation, erythema or scaling)

• = almost clear (minimal plaque elevation, erythema or scaling)
• = mild (mild plaque elevation or scaling, light red coloration)
• = moderate (moderate plaque elevation, scaling, light red coloration)
• = marked (marked plaque elevation, thick, non-tenacious scale predominates, bright red coloration)
• = severe (severe plaque elevation, very thick tenacious scaling, dusky to deep red coloration).

The static Physician Global Assessment of psoriasis (sPGA) evaluates the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA is assessed on a scale from 0 to 5:

0 = clear (no evidence of plaque elevation, erythema or scaling)

• = almost clear (minimal plaque elevation, erythema or scaling)
• = mild (mild plaque elevation or scaling, light red coloration)
• = moderate (moderate plaque elevation, scaling, light red coloration)
• = marked (marked plaque elevation, thick, non-tenacious scale predominates, bright red coloration)
• = severe (severe plaque elevation, very thick tenacious scaling, dusky to deep red coloration).

The static Physician Global Assessment of psoriasis (sPGA) evaluates the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The sPGA is assessed on a scale from 0 to 5:

0 = clear (no evidence of plaque elevation, erythema or scaling)

• = almost clear (minimal plaque elevation, erythema or scaling)
• = mild (mild plaque elevation or scaling, light red coloration)
• = moderate (moderate plaque elevation, scaling, light red coloration)
• = marked (marked plaque elevation, thick, non-tenacious scale predominates, bright red coloration)
• = severe (severe plaque elevation, very thick tenacious scaling, dusky to deep red coloration).