Efficacy And Safety Of Tofacitinib In Chinese Subjects With Active Psoriatic Arthritis

ACR50 response: greater than or equal to (≥) 50% improvement in tender (TJC) and swollen joint counts (SJC) and ≥50% improvement in 3 of the 5 remaining ACR-core set measures: patient (PtGA) and physician global assessments (PhyGA), pain, disability (Health Assessment Questionnaire - Disability Index \[HAQ-DI\], scored from 0 to 3), and an acute-phase reactant (C-reactive protein \[CRP\]). TJC was based on 68 joints and SJC was based on 66 joints. PtGA, PhyGA and Pain were VAS on a scale of 0-100 millimeter (mm).

Time frame: Month 3

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Missing response (MR) was considered to be non-response (NR) (MR=NR).

Blood samples were collected at each visit (except follow-up) for analysis of CRP using an assay by the central laboratory. The test for CRP was a laboratory measurement for evaluation of an acute phase reactant of inflammation. A decrease in the level of CRP indicated reduction in inflammation and therefore improvement.

Time frame: Baseline, Week 2, Month 1, 2, 3, 4, and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Here Number of Participants Analyzed indicates participants included in the MMRM.~Here Number analyzed signifies participants evaluable for this OM at the specific visit.

The DAS was a derived measurement with differential weighting given to each component. The components of the DAS 28-3 arthritis assessment were: Tender/Painful Joint Count (28), Swollen Joint Count (28), CRP (refer to above OMs for more details of these components). DAS28 scores range from 0 to 9.4. A DAS28-3 (CRP) score higher than 5.1 indicates high disease activity, a DAS28-3 (CRP) score less than 3.2 indicates low disease activity, and a DAS28-3 (CRP) score less than 2.6 indicates clinical remission. A higher score represented a more severe disease activity, and a negative change from baseline indicates improvement. DAS28-3(CRP)=\[0.56\*sqrt(TJC28)+0.28\*sqrt(SJC28)+0.36\*ln(CRP+1)\]\*1.10+1.15, where sqrt() refers to the square root, and ln() refers to the natural logarithm.

Time frame: Baseline, Week 2, Month 1, 2, 3, 4, and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Here Number of Participants Analyzed indicates participants included in the MMRM.~Here Number analyzed signifies participants evaluable for this OM at the specific visit.

Dactylitis was characterized by swelling of the entire finger or toe. The DSS was a function of finger circumference and tenderness, assessed and summed across all dactylitis digits. Dactylitis severity was scored based upon digit tenderness using a scale of 0-3, where 0 = no tenderness and 3 = extreme tenderness, in each digit of the hands and feet. DSS was the sum of the severity of the 20 evaluated digits. The range of total dactylitis scores for a participant would be 0-60 (with a higher score indicating more severe dactylitis).

Time frame: Baseline, Month 1, 3 and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Analysis only included participants in FAS with Baseline DSS \>0. Here Number of Participants Analyzed indicates participants included in the MMRM.~Here Number analyzed signifies participants evaluable for this OM at the specific visit.

On the EQ-5D (participant version, 3 categories of response per question), 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) were assessed. The status of each dimension had three possible responses with the corresponding scores of 1 (no problem), 2 (some problems) and 3 (severe problems).

Time frame: Baseline, Month 1, 3 and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Here Number of Participants Analyzed indicates participants included in the MMRM.~Here Number analyzed signifies participants evaluable for this OM at the specific visit.

The EQ-VAS recorded the patient's self-rated health on a vertical visual analogue scale where the endpoint was labelled 'Best imaginable health state' and 'Worst imaginable health state'. Based on the patient's mark on the VAS form a score ranging from 0 to 100 mm was recorded.

Time frame: Baseline, Month 1, 3 and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Here Number of Participants Analyzed indicates participants included in the MMRM.~Here Number analyzed signifies participants evaluable for this OM at the specific visit.

The HAQ-DI assessed the degree of difficulty a participant had experienced during the past week in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. For each question in the questionnaire, the level of difficulty was scored from 0 to 3 with 0 representing no difficulty, 1 as some difficulty, 2 as much difficulty, and 3 as unable to do. The HAQ-DI score was the average of the non-missing domain scores. If \>2 domain scores were missing, HAQ-DI score was considered missing. A higher score represented a more limited physical functional status/ability.

Time frame: Baseline, Week 2, Month 1, 2, 3, 4, and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Here Number of Participants Analyzed indicates participants included in the MMRM.~Here Number analyzed signifies participants evaluable for this OM at the specific visit.

Enthesitis score based upon presence/absence of enthesitis at 6 sites using LEI. Six sites, including (right and left): lateral epicondyle humerus, medial femoral condyle and Achilles tendon insertion, were assessed for enthesitis. LEI was the number of sites with presence of enthesitis.

Time frame: Baseline, Month 1, 3 and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Analysis only included participants in FAS with Baseline LEI \>0. Here Number of Participants Analyzed indicates participants included in the MMRM.~Here Number analyzed signifies participants evaluable for this OM at the specific visit.

A target finger nail was evaluated using NAPSI scale. Each quadrant of the target nail was graded for nail matrix psoriasis and nail bed psoriasis, giving that 1 target nail a score of 0-8. At the baseline visit, the worst case fingernail was chosen and the same nail evaluated consistently through the entire study.

Time frame: Baseline, Month 1, 3 and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Analysis only included participants in FAS with Baseline NAPSI \>0. Here Number of Participants Analyzed indicates participants included in the MMRM.~Here Number analyzed signifies participants evaluable for this OM at the specific visit.

Participants were assessed the severity of their arthritis pain using a 100 mm VAS by placing a mark on the scale between 0 (no pain) and 100 (most severe pain).

Time frame: Baseline, Week 2, Month 1, 2, 3, 4, and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Here Number of Participants Analyzed indicates participants included in the MMRM.~Here Number analyzed signifies participants evaluable for this OM at the specific 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 VAS by placing a mark on the scale between 0 (Very well) and 100 (Very poorly).

Time frame: Baseline, Week 2, Month 1, 2, 3, 4, and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Here Number of Participants Analyzed indicates participants included in the MMRM.~Here Number analyzed signifies participants evaluable for this OM at the specific visit.

The PGA-PsO was scored on a 5-point scale, reflecting a global consideration of the erythema, induration and scaling across all psoriatic lesions. Average erythema, induration and scaling were scored separately over the whole body according to a 5-point severity scale, scored as 0 (none), 1, 2, 3, or 4 (most severe). The severity scores were summed and averaged after which the total average was rounded to the nearest whole number score to determine the PGA-PsO score.

Time frame: Baseline, Month 1, 3 and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo). Analysis only included participants in FAS with Baseline PGA-PsO \>0.~Here Number of Participants Analyzed indicates participants included in the MMRM.~Here Number analyzed signifies participants evaluable for this OM at the specific visit.

The blinded investigator or qualified assessor assessed how the participant's overall arthritis appeared at the time of the visit. This was an evaluation based on the participant's disease signs, functional capacity and physical examination, and should be independent of the Patient's Global Assessment of Arthritis. The investigator's response was recorded using a 100 mm VAS by placing a mark on the scale between 0 (Very good) and 100 (Very poor).

Time frame: Baseline, Week 2, Month 1, 2, 3, 4, and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Here Number of Participants Analyzed indicates participants included in the MMRM.~Here Number analyzed signifies participants evaluable for this OM at the specific visit.

The blinded investigator or qualified assessor assessed how the participant's overall PsA appeared at the time of the visit. The investigator's response was recorded using a 100 mm VAS (Not active at all to Extremely active).

Time frame: Baseline, Month 1, 3 and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Here Number of Participants Analyzed indicates participants included in the MMRM.~Here Number analyzed signifies participants evaluable for this OM at the specific visit.

The SF 36 v.2 (Acute) was a 36 item generic health status measure. It measured 8 general health domains: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. These domains were summarized as physical and mental component summary scores. The score range for the physical and mental health scores was 0-100 (100=highest level of functioning).

Time frame: Baseline, Month 1, 3 and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Here Number of Participants Analyzed indicates participants included in the MMRM.~Here Number analyzed signifies participants evaluable for this OM at the specific visit.

Swollen joint count was an assessment on 66 joints (temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeals, thumb interphalangeal, proximal interphalangeals, distal interphalangeals, knee, ankle, tarsus, metatarsophalangeals, great toe interphalangeal, proximal and distal interphalangeals combined). Artificial joints were not assessed. Each joint was assessed for swelling as: Present/Absent/Not Done/Not Applicable (used for artificial or missing joints).

Time frame: Baseline, Week 2, Month 1, 2, 3, 4, and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Here Number of Participants Analyzed indicates participants included in the MMRM.~Here Number analyzed signifies participants evaluable for this OM at the specific visit.

Tender/painful joint count was an assessment on 68 joints (temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeals, thumb interphalangeal, proximal interphalangeals, distal interphalangeals, hip, knee, ankle, tarsus, metatarsophalangeals, great toe interphalangeal, proximal and distal interphalangeals combined). Artificial joints were not assessed. Each joint was assessed for tenderness/pain as: Present/Absent/Not Done/Not Applicable (used for artificial or missing joints).

Time frame: Baseline, Week 2, Month 1, 2, 3, 4, and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Here Number of Participants Analyzed indicates participants included in the MMRM.~Here Number analyzed signifies participants evaluable for this OM at the specific visit.

The WPAI-PsA was a 6-item questionnaire that measured absenteeism (work time missed), presenteesism (impairment at work/reduced on -the-job effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism) and activity impairment. WPAI-PsA outcomes were expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.

Time frame: Baseline, Month 3 and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Here Number of Participants Analyzed indicates participants included in the MMRM.~Here Number analyzed signifies participants evaluable for this OM at the specific visit.

The WPAI-PsA was a 6-item questionnaire that measured absenteeism (work time missed), presenteesism (impairment at work/reduced on-the-job effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism) and activity impairment. WPAI-PsA outcomes were expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.

Time frame: Baseline, Month 3 and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Here Number of Participants Analyzed indicates participants included in the MMRM.~Here Number analyzed signifies participants evaluable for this OM at the specific visit.

Rate was measured in terms of percentage of participants with HAQ-DI response. The HAQ-DI assessed the degree of difficulty a participant had experienced during the past week in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. For each question in the questionnaire, the level of difficulty was scored from 0 to 3 with 0 representing no difficulty, 1 as some difficulty, 2 as much difficulty, and 3 as unable to do. The HAQ-DI score was the average of the non-missing domain scores. If \>2 domain scores were missing, HAQ-DI score was considered missing. A higher score represented a more limited physical functional status/ability.

Time frame: Week 2, Month 1, 2, 3, 4, and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Analysis only included participants in FAS with Baseline HAQ-DI ≥0.30. MR was considered to be NR (MR=NR).

Rate was measured in terms of percentage of participants with HAQ-DI response. The HAQ-DI assessed the degree of difficulty a participant had experienced during the past week in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. For each question in the questionnaire, the level of difficulty was scored from 0 to 3 with 0 representing no difficulty, 1 as some difficulty, 2 as much difficulty, and 3 as unable to do. The HAQ-DI score was the average of the non-missing domain scores. If \>2 domain scores were missing, HAQ-DI score was considered missing. A higher score represented a more limited physical functional status/ability.

Time frame: Week 2, Month 1, 2, 3, 4, and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Analysis only included participants in FAS with Baseline HAQ-DI ≥0.35. MR was considered to be NR (MR=NR).

ACR20 response:≥20% improvement in TJC and SJC and ≥20% improvement in 3 of the 5 remaining ACR-core set measures: PtGA and PhyGA, pain, disability (HAQ-DI, scored from 0 to 3), and a CRP. TJC was based on 68 joints and SJC was based on 66 joints. PtGA, PhyGA and Pain were VAS on a scale of 0-100 mm.

Time frame: Week 2, Month 1, 2, 3, 4, and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~MR was considered to be NR (MR=NR).

ACR50 response:≥50% improvement in TJC and SJC and ≥50% improvement in 3 of the 5 remaining ACR-core set measures: PtGA and PhyGA, pain, disability (HAQ-DI, scored from 0 to 3), and a CRP. TJC was based on 68 joints and SJC was based on 66 joints. PtGA, PhyGA and Pain were VAS on a scale of 0-100 mm.

Time frame: Week 2, Month 1, 2, 4, and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~MR was considered to be NR (MR=NR).

ACR70 response:≥70% improvement in TJC and SJC and ≥70% improvement in 3 of the 5 remaining ACR-core set measures: PtGA and PhyGA, pain, disability (HAQ-DI, scored from 0 to 3), and a CRP. TJC was based on 68 joints and SJC was based on 66 joints. PtGA, PhyGA and Pain were VAS on a scale of 0-100 mm.

Time frame: Week 2, Month 1, 2, 3, 4, and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~MR was considered to be NR (MR=NR).

The PsARC consisted of 4 measurements: Tender Joint Count (68), Swollen Joint Count (66), Physician's Global Assessment of Arthritis (VAS) (0-100 mm), Patient's Global Assessment of Arthritis (VAS) (0-100 mm). In order to be a 'PsARC responder', participant must achieve improvement in 2 of 4 measures, one of which must be joint pain or swelling, without worsening in any measure.

Time frame: Week 2, Month 1, 2, 3, 4, and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~MR was considered to be NR (MR=NR).

Assessment of BSA with psoriasis was performed separately for four body regions: head and neck, upper limbs, trunk (including axillae and groin), and lower limbs (including buttocks). The BSA with psoriasis (%) was the sum of the numbers of the handpoints across the 4 body regions.

Time frame: Baseline, Month 1, 3 and 6

Population: The unit of Percentage is for percent change from baseline: (change from baseline / baseline value)\*100% FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo). Analysis only included participants in FAS with Baseline BSA \>0%.~Here Number of Participants Analyzed indicates participants included in the MMRM.~Here Number analyzed signifies participants evaluable for this OM at the specific visit.

PASI quantified the severity of a participant's psoriasis based on both lesion severity and the percentage of BSA affected. PASI was a composite scoring by the investigator of degree of erythema, induration, and scaling (each scored separately) for each of four body regions, with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. PASI was only performed if ≥3% of participant's BSA was affected at baseline. The PASI clinical component scores (erythema, induration and scaling) range from 0.0 to 24.0, with higher scores representing increasing severity of psoriasis.

Time frame: Baseline, Month 1, 3 and 6

Population: The unit of Percentage is for percent change from baseline: (change from baseline / baseline value)\*100% FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo). Analysis only included participants in FAS with Baseline BSA ≥3% and Baseline PASI \>0.~Here Number of Participants Analyzed indicates participants included in the MMRM.~Here Number analyzed signifies participants evaluable for this OM at the specific visit.

PASI quantified the severity of a participant's psoriasis based on both lesion severity and the percentage of BSA affected. PASI was a composite scoring by the investigator of degree of erythema, induration, and scaling (each scored separately) for each of four body regions, with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. PASI score ranged from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. PASI was only performed if ≥3% of participant's BSA was affected at baseline.

Time frame: Baseline, Month 1, 3 and 6

Population: The unit of Percentage is for percent change from baseline: (change from baseline / baseline value)\*100% FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo). Analysis only included participants in FAS with Baseline BSA ≥3% and Baseline PASI \>0.~Here Number of Participants Analyzed indicates participants included in the MMRM.~Here Number analyzed signifies participants evaluable for this OM at the specific visit.

PGA-PsO response : PGA-PsO = 0 or 1 and decrease from baseline in PGA-PsO ≥2. Rate was measured in terms of percentage of participants with PGA-PsO response. The PGA-PsO was scored on a 5-point scale, reflecting a global consideration of the erythema, induration and scaling across all psoriatic lesions. Average erythema, induration and scaling were scored separately over the whole body according to a 5-point severity scale, scored as 0 (none), 1, 2, 3, or 4 (most severe). The severity scores were summed and averaged after which the total average was rounded to the nearest whole number score to determine the PGA-PsO score.

Time frame: Month 1, 3 and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Analysis only included participants in FAS with Baseline PGA-PsO ≥2. MR was considered to be NR (MR=NR).

PASI75 response: ≥75% improvement from baseline in PASI. Rate was measured in terms of percentage of participants with PASI75 response. PASI quantified the severity of a participant's psoriasis based on both lesion severity and the percent of BSA affected. PASI score ranged from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. PASI was only performed if ≥3% of participant's BSA was affected at baseline.

Time frame: Month 1, 3 and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Analysis only included participants in FAS with Baseline BSA ≥3% and Baseline PASI \>0.~MR was considered to be NR (MR=NR).

Dactylitis was characterized by swelling of the entire finger or toe. The DSS was a function of finger circumference and tenderness, assessed and summed across all dactylitis digits. Resolution rate of dactylitis was defined as achieving DSS =0. Rate was measured in terms of percentage of participants with resolution of dactylitis. Dactylitis severity was scored based upon digit tenderness using a scale of 0-3, where 0 = no tenderness and 3 = extreme tenderness, in each digit of the hands and feet. DSS was the sum of the severity of the 20 evaluated digits. The range of total dactylitis scores for a participant would be 0-60 (with a higher score indicating more severe dactylitis).

Time frame: Month 1, 3 and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Analysis only included participants in FAS with Baseline DSS \>0. MR was considered to be NR (MR=NR).

Resolution rate of enthesitis was defined as percentage of participants achieving enthesitis score (using LEI) =0. Rate was measured in terms of percentage of participants with resolution of enthesitis. Enthesitis score based upon presence/absence of enthesitis at 6 sites using LEI. Six sites, including (right and left): lateral epicondyle humerus, medial femoral condyle and Achilles tendon insertion, were assessed for enthesitis. LEI was the number of sites with presence of enthesitis.

Time frame: Month 1, 3 and 6

Population: FAS: included all participants randomized and who have received at least one dose of randomized study drug (tofacitinib or placebo).~Analysis only included participants in FAS with Baseline LEI \>0. MR was considered to be NR (MR=NR).