A Study to Evaluate the Efficacy and Safety of PF-06700841 in Subjects With Active Psoriatic Arthritis

ACR 20 was calculated as a ≥20% improvement in tender and swollen joint counts and ≥20% improvement in 3 of the 5 remaining ACR core set measures: patient pain assessment (a horizontal visual analog scale assessment of the patient's level of pain), patient global assessment (the patient's overall assessment of how the arthritis was doing by a visual analog scale), physician global assessment (a horizontal visual analog scale measure of the physician's assessment of the patient's current disease activity), patient self-assessed disability (a validated and reliable patient self-assessment instrument which measured physical functions in rheumatoid arthritis patients) and an acute-phase reactant (C-reactive protein level). The participants receiving placebo in the initial period (Day 1 - Week 16) were combined into a single placebo group, while those who received PF-06700841 (10 mg QD) in the initial period were combined into a single PF-06700841 10 mg QD group.

Time frame: Week 16

Population: All participants who received at least 1 dose of the randomized study treatment.

The HAQ-DI assessed the degree of difficulty a participant experienced in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consists of 2-3 items. For each question in the questionnaire, the level of difficulty is scored from 0 to 3 with 0 representing no difficulty, 1 as some difficulty, 2 as much difficulty, and 3 as unable to do. Any activity that requires assistance from another individual or requires the use of an assistive device adjusts to a minimum score of 2 to represent a more limited functional status. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range was 0 to 3, with a higher score indicating more difficulty in performing daily living activities. A negative change from baseline represents improvement.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 28, 36, 44 and 52

Population: Overall Number of Participants Analyzed indicated the evaluable population and included all participants who were randomized to the study and received at least one dose of the randomized study treatment. Number Analyzed included participants available in the evaluable population at each specified visit.

C-reactive protein (hsCRP) is an acute phase reactant, which is indicative of inflammation and of its severity. Blood samples were obtained at Baseline, Weeks 2, 4, 8, 12, 16, 20, 28, 36, 44 and 52 for determination of hsCRP.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 28, 36, 44 and 52

Population: Overall Number of Participants Analyzed included all the participants in the pharmacodynamic (PD) analysis population who received at least one dose of randomized study treatment and in whom at least one value of the PD parameter of interest was reported. Number Analyzed included participants available in the PD analysis population at each specified visit.

Participants assessed the severity of their arthritis pain using a 100 millimeter (mm) visual analog scale (VAS) by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain. VAS data was rescaled prior to any calculation and analysis. Rescaled VAS score (mm) = (100 mm) × (length at mark in mm/overall length of line in mm). The score range was 0 mm to 100 mm, with a higher score indicating a higher degree of pain. A negative change from baseline represents improvement.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 28, 36, 44 and 52

Population: Overall Number of Participants Analyzed indicated the evaluable population and included all participants who were randomized to the study and received at least one dose of the randomized study treatment. Number Analyzed included participants available in the evaluable population at each specified visit.

Participants answered the following question, Considering all the ways your arthritis affects you, how are you feeling today?. The participant's response was recorded using a 100 mm visual analog scale (VAS) by placing a mark on the scale between 0 (very well) and 100 (very poorly). VAS data was rescaled prior to any calculation and analysis. Rescaled VAS score (mm) = (100 mm) × (length at mark in mm/overall length of line in mm). The score range was 0 mm to 100 mm, and a negative change from baseline represents improvement.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 28, 36, 44 and 52

Population: Overall Number of Participants Analyzed indicated the evaluable population and included all participants who were randomized to the study and received at least one dose of the randomized study treatment. Number Analyzed included participants available in the evaluable population at each specified visit.

The blinded assessor assessed the participant's overall arthritis appears at the time of each visit. This was an evaluation based on the participant's disease signs, functional capacity and physical examination, and was independent of the Patient's Global Assessment of Arthritis. The investigator's response was recorded using a 100 mm visual analog scale (VAS) by placing a mark on the scale between 0 (very good) and 100 (very poor). VAS data was rescaled prior to any calculation and analysis. Rescaled VAS score (mm) = (100 mm) × (length at mark in mm/overall length of line in mm). The score range was 0 mm to 100 mm, and a negative change from baseline represents improvement.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 28, 36, 44 and 52

Population: Overall Number of Participants Analyzed indicated the evaluable population and included all participants who were randomized to the study and received at least one dose of the randomized study treatment. Number Analyzed included participants available in the evaluable population at each specified visit.

The swollen joints were assessed by a blinded assessor to determine the number of joints that were considered swollen using the following scale: Present/Absent/Not Done/Not Applicable (used for artificial or missing joints). Artificial joints was not assessed. Injected joints was counted according to their pre-injection status for the remainder of the study. The assessment was based on 66 joints. The score range was 0 to 66, with a higher score indicating a greater degree of swelling. A negative change from baseline represents improvement.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 28, 36, 44 and 52

Population: Overall Number of Participants Analyzed indicated the evaluable population and included all participants who were randomized to the study and received at least one dose of the randomized study treatment. Number Analyzed included participants available in the evaluable population at each specified visit.

The tender/painful joints were assessed by a blinded assessor to determine the number of joints that were considered tender/painful using the following scale: Present/Absent/Not Done/Not Applicable (used for artificial or missing joints). Artificial joints was not assessed. Injected joints was counted according to their pre-injection status for the remainder of the study. The assessment was based on 68 joints. The score range was 0 to 68, with a higher score indicating a greater degree of tenderness. A negative change from baseline represents improvement.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 28, 36, 44 and 52

Population: Overall Number of Participants Analyzed indicated the evaluable population and included all participants who were randomized to the study and received at least one dose of the randomized study treatment. Number Analyzed included participants available in the evaluable population at each specified visit.

The number of digits in hands and feet with dactylitis was evaluated by a blinded assessor. In addition, dactylitis severity was scored based upon digit tenderness using a scale of 0-3, where 0 = no tenderness to 3 = extreme tenderness, in each digit of the hands and feet. The range of total dactylitis scores was 0-60, with higher scores indicating greater severity. A negative change from baseline represents improvement.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 28, 36, 44 and 52

Population: Overall Number of Participants Analyzed included all the participants in evaluable population (participants who were randomized to the study and received at least one dose of the randomized study treatment) with baseline DSS \>0. Number Analyzed included participants available in the evaluable population at each specified treatment timepoints with baseline DSS \>0.

DAREA/DAPSA is a composite instrument to assess peripheral joint involvement that is based upon numerical summation of 5 variables of disease activity: tender/painful joint count + swollen joint count (using SJC66/ TJC68 assessments), Patient's Global Assessment of Arthritis (PtGA in cm), Patient's Assessment of Arthritis Pain (PAIN in cm) and C-reactive protein (CRP) (in mg/dL). Since DAREA reflects domains found important in PsA, it has been proposed to serve as a Disease Activity Index for Psoriatic Arthritis (DAPSA). DAREA/DAPSA was calculated as follows: DAREA/DAPSA= SJC66 + TJC68 + PtGA + PAIN + CRP. A negative change from baseline represents improvement.

Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 28, 36, 44 and 52

Population: Overall Number of Participants Analyzed included all the participants in the evaluable population (participants who were randomized to the study and received at least one dose of the randomized study treatment) with baseline DAREA/DAPSA. Number Analyzed included participants available in the evaluable population at each specified treatment timepoints with baseline DAREA/DAPSA.

The Leeds Enthesitis Index (LEI) examines tenderness at six sites: lateral epicondyle humerus, medial femoral condyle and Achilles tendon insertion. Each site is assessed as either tender (score=1) or not tender (score=0). The LEI scores range from 0-6, with higher scores indicating higher disease activity.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 28, 36, 44 and 52

Population: Overall Number of Participants Analyzed included all the participants in the evaluable population (participants who were randomized to the study and received at least one dose of the randomized study treatment) with baseline leeds enthesitis score\>0. Number Analyzed included participants available in the evaluable population at each specified treatment timepoints with baseline leeds enthesitis score\>0.

The SPARCC Enthesitis Index examines tenderness at sixteen sites: medial epicondyle humerus, lateral epicondyle humerus, supraspinatus insertion into greater tuberosity of humerus, greater trochanter, quadriceps insertion into superior border of patella, patellar ligament insertion into inferior pole of patella or tibial tubercle (considered 1 site for scoring purposes), Achilles tendon insertion into calcaneum and plantar fascia insertion into calcaneum. Each site is classified on a dichotomous basis as either tender (score=1) or not tender (score=0). The SPARCC Enthesitis Index scores range from 0-16, with higher scores indicating higher disease activity.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 28, 36, 44 and 52

Population: Overall Number of Participants Analyzed included all the participants in the evaluable population (participants who were randomized to the study and received at least one dose of the randomized study treatment) with baseline SPARCC enthesitis score\>0. Number Analyzed included participants available in the evaluable population at each specified treatment timepoints with baseline SPARCC enthesitis score \>0.

The FACIT-F Scale is a patient completed questionnaire consisting of 13 items that assess fatigue. Participants responded to each item on a 5-point scale based on their experience of fatigue during the past 7 days (0 = not at all; 1 = a little bit; 2 =somewhat; 3 = quite a bit; 4 = very much). Instrument scoring yielded a range from 0 to 52 (negatively worded items were reversed during analysis), with higher scores representing better participant status (less fatigue).

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 28, 36, 44 and 52

Population: Overall Number of Participants Analyzed indicated the evaluable population and included all participants who were randomized to the study and received at least one dose of the randomized study treatment. Number Analyzed included participants available in the evaluable population at each specified visit.

A target finger nail was evaluated by the blinded assessor using the NAPSI scale. At the baseline visit, the worst case fingernail was chosen and the same nail was evaluated consistently through the entire study. Each quadrant of the target nail was graded for nail matrix psoriasis (including any of the following parameters: pitting, leukonychia, red spots in lunula, nail plate crumbling) and nail bed psoriasis (including any of the following parameters: onycholysis, splinter hemorrhages, oil drop (salmon patch) discoloration, nail bed hyperkeratosis). The target nail NAPSI scores range from 0 to 8, with higher scores indicating higher disease activity.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 28, 36, 44 and 52

Population: Overall Number of Participants Analyzed included all the participants in evaluable population (participants who were randomized to the study and received at least one dose of the randomized study treatment) with baseline NAPSI\>0. Number Analyzed included participants available in the evaluable population at each specified treatment timepoints with baseline NAPSI\>0.

Participant's perception of disease was assessed using a 100 mm visual analog scale (VAS) by placing a mark on the scale between 0 (excellent) and 100 (poor). The rating corresponded to the way in which the participant felt over the past week in terms of how they were affected by their: 1) psoriasis and arthritis (global, PGA); 2) arthritis only (PJA) and 3) psoriasis only (PSA). Rescaled VAS score was used. Rescaled VAS score (mm) = (100 mm) × (length at mark in mm/overall length of line in mm). A negative change from baseline represents improvement.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 28, 36, 44 and 52

Population: Overall Number of Participants Analyzed indicated the evaluable population and included all participants who were randomized to the study and received at least one dose of the randomized study treatment. Number Analyzed included participants available in the evaluable population at each specified visit.

PASDAS is a composite psoriatic arthritis disease activity score that includes the following components: patient's global joint and skin assessment (visual analog scale in mm), physician's global psoriatic arthritis assessment (visual analog scale in mm), swollen (66 joints) and tender joint counts (68 joints), Leeds Enthesitis Index score, tender dactylitic digit score, physical component summary score (PCS) of Short Form 36 Health Survey and C-reactive protein (mg/L). Any missing component would result in PASDAS as missing. A higher PASDAS score indicates a higher disease activity.

Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 28, 36, 44 and 52

Population: Overall Number of Participants Analyzed indicated the evaluable population and included all participants who were randomized to the study and received at least one dose of the randomized study treatment. Number Analyzed included participants available in the evaluable population at each specified treatment timepoints.

The SF-36 version 2 (Acute version) is a 36-item generic health status measure. It measures 8 general health concepts or domains: Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH). These 8 domains can also be summarized as physical and mental component scores. The summary component scores, Physical Component Summary (PCS) and Mental Component Summary (MCS), are based on a normalized sum of the 8 scale scores PF, RP, BP, GH, VT, SF, RE, and MH. All domains and summary components are scored such that a higher score indicates a higher functioning or health level. The minimum and maximum scores of the PCS Score are 22 and 59 respectively. The minimum and maximum scores of the MCS Score are 11 and 62 respectively.

Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 28, 36, 44 and 52

Population: Overall Number of Participants Analyzed indicated the evaluable population and included all participants who were randomized to the study and received at least one dose of the randomized study treatment. Number Analyzed included participants available in the evaluable population at each specified visit.

An AE is any untoward medical occurrence in a study participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of the study medication.

Time frame: Baseline (Day 1) through Week 56

Population: All participants who received at least one dose of the randomized study treatment.

Treatment-emergent AEs are those with initial onset or that worsen in severity after the first dose of the study medication. All AEs in the table below were treatment-emergent AEs. An SAE is any untoward medical occurrence at any dose that: results in death; is life threatening (immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); results in congenital anomaly/birth defect; or that is considered to be an important medical event that may jeopardize the participant or may require intervention to prevent one of the other AE outcomes. Severe AEs were defined as AEs that interfered significantly with participant's usual function. Both SAEs and severe AEs were according to the investigator's assessment.

Time frame: Baseline (Day 1) through Week 56

Population: All participants who received at least one dose of the randomized study treatment.

Treatment-emergent AEs are those with initial onset or that worsen in severity after the first dose of the study medication. All AEs in the table below were treatment-emergent AEs. An SAE is any untoward medical occurrence at any dose that: results in death; is life threatening (immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); results in congenital anomaly/birth defect; or that is considered to be an important medical event that may jeopardize the participant or may require intervention to prevent one of the other AE outcomes. Severe AEs were defined as AEs that interfered significantly with participant's usual function. Both SAEs and severe AEs were according to the investigator's assessment. Treatment-related AEs were also determined by the investigator.

Time frame: Baseline (Day 1) through Week 56

Population: All participants who received at least one dose of the randomized study treatment.

ACR 20 was calculated as a ≥20% improvement in tender and swollen joint counts and ≥20% improvement in 3 of the 5 remaining ACR core set measures: patient pain assessment (a horizontal visual analog scale assessment of the patient's level of pain), patient global assessment (the patient's overall assessment of how the arthritis was doing by a visual analog scale), physician global assessment (a horizontal visual analog scale measure of the physician's assessment of the patient's current disease activity), patient self-assessed disability (a validated and reliable patient self-assessment instrument which measured physical functions in rheumatoid arthritis patients) and an acute-phase reactant (C-reactive protein level). The participants receiving placebo in the initial period (Day 1 - Week 16) were combined into a single placebo group, while those who received PF-06700841 (10 mg QD) in the initial period were combined into a single PF-06700841 10 mg QD group.

Time frame: Week 16

Population: All participants who received at least 1 dose of the randomized study treatment with prior TNFα naïve.

The American College of Rheumatology's definition for calculating improvement in rheumatoid arthritis (ACR20) was calculated as a ≥20% improvement in tender and swollen joint counts and ≥20% improvement in 3 of the 5 remaining ACR core set measures: patient pain assessment (a horizontal visual analog scale assessment of the patient's level of pain), patient global assessment (the patient's overall assessment of how the arthritis was doing by a visual analog scale), physician global assessment (a horizontal visual analog scale measure of the physician's assessment of the patient's current disease activity), patient self-assessed disability (a validated and reliable patient self-assessment instrument which measured physical functions in rheumatoid arthritis patients) and an acute-phase reactant (C-reactive protein level).

Time frame: Weeks 2, 4, 8, 12, 20, 28, 36, 44 and 52

Population: All participants who received at least 1 dose of the randomized study treatment.

The American College of Rheumatology's definition for calculating improvement in rheumatoid arthritis (ACR50) was calculated as a ≥50% improvement in tender and swollen joint counts and ≥50% improvement in 3 of the 5 remaining ACR core set measures: patient pain assessment (a horizontal visual analog scale assessment of the patient's level of pain), patient global assessment (the patient's overall assessment of how the arthritis was doing by a visual analog scale), physician global assessment (a horizontal visual analog scale measure of the physician's assessment of the patient's current disease activity), patient self-assessed disability (a validated and reliable patient self-assessment instrument which measured physical functions in rheumatoid arthritis patients) and an acute-phase reactant (C-reactive protein level).

Time frame: Weeks 2, 4, 8, 12, 16, 20, 28, 36, 44 and 52

Population: All participants who received at least 1 dose of the randomized study treatment.

The American College of Rheumatology's definition for calculating improvement in rheumatoid arthritis (ACR70) was calculated as a ≥70% improvement in tender and swollen joint counts and ≥70% improvement in 3 of the 5 remaining ACR core set measures: patient pain assessment (a horizontal visual analog scale assessment of the patient's level of pain), patient global assessment (the patient's overall assessment of how the arthritis was doing by a visual analog scale), physician global assessment (a horizontal visual analog scale measure of the physician's assessment of the patient's current disease activity), patient self-assessed disability (a validated and reliable patient self-assessment instrument which measured physical functions in rheumatoid arthritis patients) and an acute-phase reactant (C-reactive protein level).

Time frame: Weeks 2, 4, 8, 12, 16, 20, 28, 36, 44 and 52

Population: All participants who received at least 1 dose of the randomized study treatment.