Efficacy Study Of Tofacitinib In Pediatric JIA Population

Pfizer225 enrolled

Overview

Evaluate efficacy, safety and tolerability of tofacitinib in pediatric JIA patients.

This is a randomized withdrawal, double blind, placebo controlled study of pediatric subjects (2 to \<18 years of age) with JIA. The primary objective is to compare the efficacy of tofacitinib versus placebo for the treatment of signs and symptoms of JIA at Week 26 of the double blind phase as measured by the percentage of subjects with disease flare (according to PRCSG/PRINTO Disease Flare criteria) after Week 18 of the open label run in phase.All eligible subjects enrolled in the study will initially receive open label tofacitinib for 18 weeks (run in phase). At the end of the 18 week run in phase, only subjects who achieve at least a JIA ACR 30 response will be randomized to the 26 week double blind, placebo controlled phase. Subjects who do not achieve a JIA ACR 30 response at this time point will be discontinued from the study. In addition, subjects who experience a single episode of disease flare at any time during the study (including the open label run in and double blind phase) will also be discontinued from the study. All subjects participating in this study, including those discontinued from the study, will have the option, if eligible (based on inclusion and exclusion criteria), of enrolling in the tofacitinib JIA long term extension study (A3921145). Subjects who are eligible for the 26 week double blind phase will be randomized (1:1 ratio) to either active tofacitinib or placebo. For subjects with polyarticular course JIA (ie, extended oligoarthritis, polyarthritis RF+, polyarthritis RF , systemic JIA with active arthritis but without active systemic features), randomization will be stratified by JIA category and baseline CRP (normal, above normal). For subjects with psoriatic and enthesitis related arthritis, randomization will be stratified by JIA category. Approximately 210 subjects will be enrolled in the open label run in phase. Among subjects with polyarticular course JIA, stratification will target at least 50% with a baseline CRP above the upper limit of normal. The first cohort (ie, polyarticular course JIA) will have at least 170 subjects enrolled in the run in phase with the minimum number of JIA categories as follows: 24 with extended oligoarthritis, 20 with polyarthritis RF+, 62 with polyarthritis RF-, and no minimum for subjects with systemic JIA with active arthritis but without active systemic features. Additional cohorts (ie, psoriatic and enthesitis related arthritis) will include a minimum of 20 subjects with psoriatic arthritis, and 20 subjects with enthesitis related arthritis. The overall target minimum number of subjects to be enrolled in the study by age is as follows: 20 subjects 2 to \<6 years, 20 subjects 6 to \<12 years, and 20 subjects 12 to \<18 years. The duration of subject participation among those who complete the study (without discontinuation) is expected to be approximately 44 weeks.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

225

Conditions

Juvenile Idiopathic Arthritis

Interventions

CP-690,550 (tofacitinib)DRUG

During the open label run in phase, all subjects will receive active tofacitinib oral tablets or oral solution twice daily (BID) orally, at a dosage based on the subject's body weight as specified below. During the double blind, placebo controlled phase, subjects will receive either active tofacitinib oral tablets/oral solution or matching placebo oral tablets/oral solution, twice daily (BID), at a dosage specified below. Body Weight (Dosage in tablet \[BID\] or solution \[BID\]): 5\<7kg (2mg or 2mL); 7\<10kg(2.5mg or 2. mL); 10 \<15kg (3mg or 3mL); 15\<25kg (3.5mg or 3.5mL); 25\<40kg (4mg or 4mL); 40kg (5 mg or 5 ml). Oral solution (1 mg/mL) is used for subjects \<40 kg. Oral tablets (5 mg) are used for subjects \>=40 kg.

placeboOTHER

matching placebo tablet or solution for tofacitinib

Eligibility

Sex: ALLMin age: 2 YearsMax age: 17 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Male or female aged 2 to \<18 years. 2. Must meet International League Against Rheumatism (ILAR) JIA diagnostic criteria for one of the following categories with active disease for at least 6 weeks: * Extended oligoarthritis; * Polyarthritis (RF+); * Polyarthritis (RF-); * Systemic JIA with active arthritis but without active systemic features in the prior 6 months and at the time of enrollment; * Psoriatic arthritis; * Enthesitis related arthritis. Subjects with polyarticular course JIA (ie, extended oligoarthritis, polyarthritis RF+, polyarthritis RF , systemic JIA with active arthritis but without active systemic features) must have a minimum of 5 active joints (an active joint is defined as a joint with swelling or, in the absence of swelling, limited range of motion accompanied by either pain on motion or tenderness) at screening and baseline to be eligible for study entry. Subjects with psoriatic or enthesitis related arthritis must have a minimum of 3 active joints (an active joint is defined as a joint with swelling or, in the absence of swelling, limited range of motion accompanied by either pain on motion or tenderness) at screening and baseline to be eligible for study entry. Treatment with stable doses of a Non Steroidal Anti inflammatory Drug (NSAID) and/or a stable dose of an oral glucocorticoid, and/or a stable dose of methotrexate is permitted. For subjects receiving an oral glucocorticoid: Glucocorticoids may be administered at a maximum dose of 0.2 mg of prednisone equivalent per kilogram per day or 10 mg per day for ≥ 2 weeks before baseline, whichever is lower. For subjects receiving methotrexate (MTX) treatment: MTX may be administered either orally or parenterally at doses not to exceed 25 mg/wk or 20 mg/m2/week (whichever is lower); participants must have taken MTX for 3 months and be at a stable dose for at least 6 weeks before baseline. Subjects taking MTX must be taking folic acid or folinic acid in accordance with local standards. For subjects with psoriatic arthritis, the following topical treatments for psoriasis are allowed: non medicated emollients for use over the whole body; topical steroids including hydrocortisone and hydrocortisone acetate ≤1% for the palms, soles, face, and intertriginous areas only; tar, salicylic acid preparations, and shampoos free of corticosteroids are permitted only for the scalp 3. Inadequate response or intolerance to at least one Disease Modifying Anti Rheumatic Drug (DMARD), which may include MTX or biologic agents; in the case of ERA and psoriatic arthritis, inadequate response to Non Steroidal Anti Inflammatory Drugs (NSAIDs). 4. No evidence or history of untreated or inadequately treated active or latent tuberculosis (TB) infection as evidenced by the following: 1. A negative QuantiFERON ®TB Gold In Tube test performed within the 3 months prior to screening. A negative purified protein derivative (PPD) test can be substituted for the QuantiFERON® TB Gold In Tube test only if the central laboratory is unable to perform the test or cannot determine the results to be positive or negative and the Pfizer medical monitor is informed and agrees on a case by case basis. 2. Chest radiograph without changes suggestive of active tuberculosis (TB) infection within 3 months prior to screening is recommended and should be performed according to local standards of care or country-specific guidelines. 3. No history of either untreated or inadequately treated latent or active TB infection. If a subject has previously received an adequate course of therapy for either latent (9 months of isoniazid in a locale where rates of primary multi drug resistant TB infection are \<5% or an acceptable alternative regimen) or active (acceptable multi drug regimen) TB infection, neither a PPD test nor a QuantiFERON-Gold®TM test need be obtained. A chest radiograph should be obtained if not done within the 3 months prior to screening. To be considered eligible for the study, the chest radiograph must be negative for active tuberculosis infection. A subject who is currently being treated for latent TB infection can only be enrolled with confirmation of current incidence rates of multi-drug resistant TB infection, documentation of an adequate treatment regimen, and prior approval of the Sponsor. 5. Fertile males and females who are, in the opinion of the investigator, sexually active and at risk for pregnancy with their partner(s) must be willing and able to use a highly effective method of contraception as outlined in this protocol during the study and for at least 28 days after the last dose of study medication. 6 Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. 7\. Evidence of a personally signed and dated Informed Consent document and Assent document (as appropriate) indicating that the subject and a legally acceptable representative/parent(s)/legal guardian has been informed of all pertinent aspects of the study. Exclusion Criteria Subjects with any of the following characteristics/conditions will not be included in the study: 1. Previous JIA treatment with tofacitinib. 2. Systemic JIA (sJIA) with active systemic features (including subjects with characteristic sJIA fever and rash or serositis within 6 months of enrollment). 3. Persistent oligoarthritis. 4. Undifferentiated JIA. 5. Infections: 1. Chronic infections; 2. Any infection requiring hospitalization, parenteral antimicrobial therapy or judged to be opportunistic by the investigator within the 6 months prior to the first dose of study drug; 3. Any treated infections within 2 weeks of Baseline visit; 4. A subject know to be infected with Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C; 5. History of infected joint prosthesis with prosthesis still in situ. 6. History of recurrent (more than one episode) herpes zoster or disseminated (at least one episode) herpes zoster, or disseminated (at least one episode) herpes simplex. 7. Active uveitis (according to SUN criteria) within 3 months of enrollment. 8. Blood dyscrasias, including: 1. Hemoglobin \<10 g/dL or Hematocrit \<33%; 2. White Blood Cell count \<3.0 x 109/L; 3. Neutrophil count \<1.2 x 109/L; 4. Platelet count \<100 x 109/L; 5. Lymphocyte count \<0.75 x 109/L. 9. Estimated glomerular filtration rate \[GFR\] \<40 mL/min/1.73 m2 at Screening. GFR will be calculated by the central lab using the bedside Schwartz formula. 10. Current or recent history of uncontrolled clinically significant renal, hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurologic disease. 11. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥1.5 times the upper limit of normal. 12. History of any other rheumatologic disease, other than Sjogren's syndrome.. 13. History or current symptoms suggestive of lymphoproliferative disorders (eg, Epstein Barr Virus \[EBV\] related lymphoproliferative disorder, lymphoma, leukemia, or signs and symptoms of current lymphatic disease). 14. Vaccinated or exposed to a live or attenuated vaccine within the 6 weeks prior to the first dose of study drug, or is expected to be vaccinated or to have household exposure to these vaccines during treatment or during the 6 weeks following discontinuation of study drug. 15. Subjects without documented evidence of having received at least one dose of the varicella vaccine in countries where the vaccine is approved and standard of care or those who do not have evidence of prior exposure to varicella zoster virus (VZV) based on serological testing (ie, VZV IgG Ab). 16. Current malignancy or history of any malignancy with the exception of adequate treated or excised basal cell or squamous cell or cervical cancer in situ. 17. Subjects who have previously failed more than 3 biologic therapies (with different mechanisms of action) for JIA. 18. Subjects with a first degree relative with a hereditary immunodeficiency; IgA deficiency not exclusionary. 19. Recent (within 28 days prior to first dose of study drug) significant trauma or major surgery. 20. Subjects receiving potent and moderate CYP3A4 inhibitors or inducers. 21. Prior treatment with non B cell specific lymphocyte depleting agents/therapies (eg, almetuzumab \[CAMPATH\], alkylating agents \[eg, cyclophosphamide or chlorambucil\], total lymphoid irradiation, etc.). Subjects who have received rituximab or other selective B lymphocyte depleting agents (including experimental agents) are eligible if they have not received such therapy for at least 1 year prior to study baseline and have normal CD 19/20+ counts by FACS analysis. 22. Use of prohibited prescription or non prescription drugs and dietary supplements listed in Appendix 1 and Appendix 4 within the specified time frame prior to the first dose of study medication. 23. Herbal supplements must be discontinued at least 28 days prior to the first dose of study medication. 24. Use of certain biologic and non biologic DMARDs are disallowed at any time during this study (Appendix 1). 25. For subjects with PsA, oral and topical medications and alternative treatments that could affect psoriasis are prohibited (see Inclusion Criterion 2 for exceptions). This includes topical corticosteroids, tars, keratolytics, anthralin, vitamin D analogs, and retinoids which must be discontinued at least 2 weeks prior to first dose of study drug. Also prohibited is ultraviolet B (UVB) (narrowband or broadband) phototherapy that must be discontinued at least 2 weeks prior to first dose of study drug. Psoralens + ultraviolet A (UVA) phototherapy (PUVA) must be discontinued at least 4 weeks prior to first dose of study drug. 26. Subjects who are children of or related to investigational site staff members, site staff members otherwise supervised by the investigator, or Pfizer employees directly involved in the conduct of the study. 27. Participation in other studies involving investigational drug(s) within 4 weeks or 5 half lives (whichever is longer) prior to study entry and/or during study participation. Exposure to investigational biologics should be discussed with the Sponsor. 28. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. 29. Pregnant or nursing females are excluded.

Locations (103)

Outcomes

Primary Outcomes

Double Blind Phase: Percentage of Participants With Disease Flare According to Pediatric Rheumatology Collaborative Study Group/Pediatric Rheumatology International Trials Organization (PRCSG/PRINTO) Disease Flare Criteria at Week 44

According to PRCSG/PRINTO, disease flare defined as worsening of \>=30 percent(%) in \>=3 of 6 variables of JIA core set, with no more than 1 variable improving by \>=30%. Six core variables: 1) Number of joints with active arthritis (joint with swelling/in absence of swelling, limited range of motion accompanied by pain/tenderness), 2)Number of joints with limited range of motion, 3) Physician global evaluation of disease activity (assessed on a Visual Analog Scale\[VAS\] of 0\[no activity\] to 10\[maximum activity\]), 4) Parent/legal guardian/participant global assessment of overall well-being (assessed on VAS of 0\[very well\] to 10\[very poor\], 5) Childhood Health Assessment Questionnaire- Disability Index (CHAQ-DI): 30 questions in 8 domains, each question answered on scale of 0=without difficulty to 3=unable to do; scores of each domain were averaged to derive total CHAQ-DI score,which ranges from 0 (minimum dysfunction) to 3 (most severe dysfunction);6) Erythrocyte Sedimentation Rate(ESR).

Time frame: Week 44

Secondary Outcomes

Double Blind Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Response at Week 44

JIA ACR50 response defined as: \>=50% improvement in 3 out of 6 JIA core set variables with no more than 1 out of 6 JIA core set variables worsened by \>=30%. Six core variables: 1) Number of joints with active arthritis (defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness), 2) Number of joints with limited range of motion, 3) Physician global evaluation of disease activity (assessed on a VAS of 0 \[no activity\] to 10 \[maximum activity\]), 4) Parent/legal guardian/participant global assessment of overall well-being (assessed on a VAS of 0 \[very well\] to 10 \[very poor\], 5) CHAQ-DI: 30 questions in 8 domains, each question answered on scale of 0=without difficulty to 3=unable to do; scores of each domain were averaged to derive total CHAQ-DI score, which ranges from 0 (minimum dysfunction) to 3 (most severe dysfunction); 6) ESR.

Data from ClinicalTrials.gov

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Arkansas Children's Hospital - Attention: Jill Hernandez

Little Rock, Arkansas, United States

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Loma Linda University Children's Hospital

Loma Linda, California, United States

Loma Linda University Clinical Trial Center

Loma Linda, California, United States

Loma Linda University Eye Institute

Loma Linda, California, United States

Loma Linda University General Pediatric Clinic - Meridian

Loma Linda, California, United States

Pediatric Specialty Team Centers of LLU Children's Hospital

Loma Linda, California, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

Pediatric Specialty Team Centers of LU Children's Hospital

San Bernardino, California, United States

Rady Children's Hospital - San Diego

San Diego, California, United States

...and 93 more locations

Double Blind Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Response at Week 44

JIA ACR30 response defined as: \>=30% improvement in 3 out of 6 JIA core set variables with no more than 1 out of 6 JIA core set variables worsened by \>=30%. Six core variables: 1) Number of joints with active arthritis (defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness), 2) Number of joints with limited range of motion, 3) Physician global evaluation of disease activity (assessed on a VAS of 0 \[no activity\] to 10 \[maximum activity\]), 4) Parent/legal guardian/participant global assessment of overall well-being (assessed on a VAS of 0 \[very well\] to 10 \[very poor\], 5) CHAQ-DI: 30 questions in 8 domains, each question answered on scale of 0=without difficulty to 3=unable to do; scores of each domain were averaged to derive total CHAQ-DI score, which ranges from 0 (minimum dysfunction) to 3 (most severe dysfunction); 6) ESR.

Time frame: Week 44

Double Blind Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Response at Week 44

JIA ACR70 response defined as: \>=70% improvement in 3 out of 6 JIA core set variables with no more than 1 out of 6 JIA core set variables worsened by \>=30%. Six core variables: 1) Number of joints with active arthritis (defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness), 2) Number of joints with limited range of motion, 3) Physician global evaluation of disease activity (assessed on a VAS of 0 \[no activity\] to 10 \[maximum activity\]), 4) Parent/legal guardian/participant global assessment of overall well-being (assessed on a VAS of 0 \[very well\] to 10 \[very poor\], 5) CHAQ-DI: 30 questions in 8 domains, each question answered on scale of 0=without difficulty to 3=unable to do; scores of each domain were averaged to derive total CHAQ-DI score, which ranges from 0 (minimum dysfunction) to 3 (most severe dysfunction); 6) ESR.

Time frame: Week 44

Double Blind Phase: JIA ACR Core Variable- Change From Double-Blind Baseline in Childhood Health Assessment Questionnaire- Disability Index (CHAQ-DI) Total Score at Week 44

CHAQ is a valid assessment of functional disability, discomfort in participants with rheumatic diseases. It comprises of three indices: Disability and Discomfort, and global assessment of arthritis (overall well-being). CHAQ-DI: as a measure of functional ability, consists of 30 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities-distributed, among a total of 30 items. Each question was rated on a 4-point scale of difficulty in performance ranges from 0 (no difficulty) to 3 (unable to do). To calculate the overall score, the participant must have a domain score in at least 6 of the 8 domains. Scores of 8 domains were averaged to calculate the CHAQ-DI total score which ranges from 0 (no or minimal physical dysfunction) to 3 (very severe physical dysfunction), higher score indicates more disability. Change from double-blind baseline at Week 44 in DI total score is reported.

Time frame: Baseline, Week 44

Open-Label Phase: Percentage of Participants With Disease Flare According to Pediatric Rheumatology Collaborative Study Group/Pediatric Rheumatology International Trials Organization (PRCSG/PRINTO) Disease Flare Criteria at Week 2, 4, 8, 12 and 18

According to PRCSG/PRINTO, disease flare defined as worsening of \>=30% in \>=3 of 6 variables of JIA core set, with no more than 1 variable improving by \>=30%. Six core variables were: 1) Number of joints with active arthritis (joint with swelling or in absence of swelling, limited range of motion accompanied by pain/ tenderness), 2) Number of joints with limited range of motion, 3) Physician global evaluation of disease activity (assessed on a VAS of 0 \[no activity\] to 10 \[maximum activity\]), 4) Parent/legal guardian/participant global assessment of overall well-being (assessed on VAS of 0 \[very well\] to 10 \[very poor\], 5) CHAQ-DI: 30 questions in 8 domains, each question answered on scale of 0=without difficulty to 3=unable to do; scores of each domain were averaged to derive total CHAQ-DI score, which ranges from 0 (minimum dysfunction) to 3 (most severe dysfunction);6) ESR.

Time frame: Weeks 2, 4, 8, 12 and 18

Double Blind Phase: Percentage of Participants With Disease Flare According to PRCSG/PRINTO Disease Flare Criteria at Week 20, 24, 28, 32, 36 and 40

Time frame: Weeks 20, 24, 28, 32, 36 and 40

Open-Label Phase: Time to Disease Flare

Time to disease flare:time (in days) from first dose of study drug until the day of disease flare in open-label phase. According to PRCSG/PRINTO, disease flare: worsening of \>=30% in \>=3 of 6 variables of JIA core set, with no more than 1 variable improving by \>=30%. 6 core variables were: 1) Number of joints with active arthritis (joint with swelling or in absence of swelling, limited range of motion accompanied by pain/ tenderness), 2) Number of joints with limited range of motion, 3) Physician global evaluation of disease activity (assessed on a VAS of 0 \[no activity\] to 10 \[maximum activity\]), 4) Parent/legal guardian/participant global assessment of overall well-being (assessed on VAS of 0 \[very well\] to 10 \[very poor\], 5) CHAQ-DI: 30 questions in 8 domains, each question answered on scale of 0=without difficulty to 3=unable to do; scores of each domain were averaged to derive total CHAQ-DI score, which ranges from 0 (minimum dysfunction) to 3 (most severe dysfunction);6) ESR.

Time frame: Day 1 up to week 18

Double Blind Phase: Time to Disease Flare

Time to disease flare: time (in days) from first dose of study drug until the day of disease flare in double blind phase. According to PRCSG/PRINTO, disease flare: worsening of \>=30% in \>=3 of 6 variables of JIA core set, with no more than 1 variable improving by \>=30%. 6 core variables were: 1) Number of joints with active arthritis (joint with swelling or in absence of swelling, limited range of motion accompanied by pain/ tenderness), 2) Number of joints with limited range of motion, 3) Physician global evaluation of disease activity (assessed on a VAS of 0 \[no activity\] to 10 \[maximum activity\]), 4) Parent/legal guardian/participant global assessment of overall well-being (assessed on VAS of 0 \[very well\] to 10 \[very poor\], 5) CHAQ-DI: 30 questions in 8 domains, each question answered on scale of 0=without difficulty to 3=unable to do; scores of each domain were averaged to derive total CHAQ-DI score, which ranges from 0 (minimum dysfunction) to 3 (most severe dysfunction);6) ESR.

Time frame: Day 1 of Week 19 up to week 44

Open-Label Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Response at Weeks 2, 4, 8, 12 and 18

Time frame: Weeks 2, 4, 8, 12 and 18

Double Blind Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Response at Double Blind Baseline, Weeks 20, 24, 28, 32, 36 and 40

Time frame: Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36 and 40

Open-Label Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Response at Weeks 2, 4, 8, 12 and 18

Time frame: Weeks 2, 4, 8, 12 and 18

Double Blind Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Response at Double Blind Baseline, Weeks 20, 24, 28, 32, 36 and 40

Time frame: Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36 and 40

Open-Label Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Response at Weeks 2, 4, 8, 12 and 18

Time frame: Weeks 2, 4, 8, 12 and 18

Double Blind Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Response at Double Blind Baseline (Week 18),Week 20, 24, 28, 32, 36 and 40

Time frame: Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36 and 40

Open-Label Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 90 Response at Week 2, 4, 8, 12 and 18

JIA ACR90 response defined as: \>=90% improvement in 3 out of 6 JIA core set variables with no more than 1 out of 6 JIA core set variables worsened by \>=30%. Six core variables: 1) Number of joints with active arthritis (defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness), 2) Number of joints with limited range of motion, 3) Physician global evaluation of disease activity (assessed on a VAS of 0 \[no activity\] to 10 \[maximum activity\]), 4) Parent/legal guardian/participant global assessment of overall well-being (assessed on a VAS of 0 \[very well\] to 10 \[very poor\], 5) CHAQ-DI: 30 questions in 8 domains, each question answered on scale of 0=without difficulty to 3=unable to do; scores of each domain were averaged to derive total CHAQ-DI score, which ranges from 0 (minimum dysfunction) to 3 (most severe dysfunction); 6) ESR.

Time frame: Weeks 2, 4, 8, 12 and 18

Double Blind Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 90 Response at Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36, 40 and 44

Time frame: Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Open-Label Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 100 Response at Week 2, 4, 8, 12 and 18

JIA ACR100 response defined as: \>=100% improvement in 3 out of 6 JIA core set variables with no more than 1 out of 6 JIA core set variables worsened by \>=30%. Six core variables: 1) Number of joints with active arthritis (defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness), 2) Number of joints with limited range of motion, 3) Physician global evaluation of disease activity (assessed on a VAS of 0 \[no activity\] to 10 \[maximum activity\]), 4) Parent/legal guardian/participant global assessment of overall well-being (assessed on a VAS of 0 \[very well\] to 10 \[very poor\], 5) CHAQ-DI: 30 questions in 8 domains, each question answered on scale of 0=without difficulty to 3=unable to do; scores of each domain were averaged to derive total CHAQ-DI score, which ranges from 0 (minimum dysfunction) to 3 (most severe dysfunction);6) ESR.

Time frame: Weeks 2, 4, 8, 12 and 18

Double Blind Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 100 Response at Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36, 40 and 44

Time frame: Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Open Label Phase: Change From Baseline in Juvenile Arthritis Disease Activity Score 27 (JADAS-27) C-Reactive Protein (CRP) Score at Weeks 2, 4, 8, 12 and 18

JADAS-27 is a validated composite disease activity measure for JIA. JADAS-27 CRP score was derived from four components; 1) Physician global assessment of disease activity (assessed on a VAS of 0 \[no activity\] to 10 \[maximum activity\]), 2) Parent/legal guardian/subject global assessment of overall well-being (assessed on a VAS of 0 \[very well\] to 10 \[very poor\]), 3) Number of joints with active disease(defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness), 4) CRP (measured in milligram per liter \[mg/L\] and value normalized to 0 to 10 scale). The overall JADAS-27 score ranges from 0-57. A higher score indicates more disease activity.

Time frame: Baseline, Weeks 2, 4, 8, 12 and 18

Double Blind Phase: Change From Double-Blind Baseline in Juvenile Arthritis Disease Activity Score (JADAS) 27 C-Reactive Protein (CRP) Score at Week 20, 24, 28, 32, 36, 40 and 44

JADAS-27 is a validated composite disease activity measure for JIA. JADAS-27 CRP score was derived from four components; 1) Physician global assessment of disease activity (assessed on a VAS of 0 \[no activity\] to 10 \[maximum activity\]), 2) Parent/legal guardian/subject global assessment of overall well-being (assessed on a VAS of 0 \[very well\] to 10 \[very poor\]), 3) Number of joints with active disease(defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness), 4) CRP (measured in mg/L and value normalized to 0 to 10 scale). The overall JADAS-27 score ranges from 0-57. A higher score indicates more disease activity.

Time frame: Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Open Label Phase: Change From Baseline in JADAS-27 Erythrocyte Sedimentation Rate (ESR) Score at Week 2, 4, 8, 12 and 18

JADAS-27 is a validated composite disease activity measure for JIA. JADAS-27 ESR score was derived from four components; 1) Physician global assessment of disease activity (assessed on a VAS of 0 \[no activity\] to 10 \[maximum activity\]), 2) Parent/legal guardian/subject global assessment of overall well-being (assessed on a VAS of 0 \[very well\] to 10 \[very poor\]), 3) Number of joints with active disease (maximum of 27 and defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness), 4) ESR. The overall JADAS-27 score ranges from 0-57. A higher score indicates more disease activity.

Time frame: Baseline, weeks 2, 4, 8, 12 and 18

Double Blind Phase: Change From Double-Blind Baseline in JADAS-27 Erythrocyte Sedimentation Rate (ESR) Score at Weeks 20, 24, 28, 32, 36, 40 and 44

Time frame: Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Open-Label Phase: Percentage of Participants With JADAS-27 CRP Minimum Disease Activity at Weeks 2, 4, 8, 12 and 18

Minimum Disease Activity is defined by a JADAS-27 CRP score less than or equal to 3.8 for participants with polyarthritis, and less than or equal to 2 for participants with oligoarthritis. JADAS-27 is a validated composite disease activity measure for JIA. JADAS-27 CRP score was derived from four components; 1) Physician global assessment of disease activity (assessed on a VAS of 0 \[no activity\] to 10 \[maximum activity\]), 2) Parent/legal guardian/subject global assessment of overall well-being (assessed on a VAS of 0 \[very well\] to 10 \[very poor\]), 3) Number of joints with active disease(maximum of 27 defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness), 4) CRP (measured in milligram per liter \[mg/L\] and value normalized to 0 to 10 scale). The overall JADAS-27 score ranges from 0-57. A higher score indicates more disease activity.

Time frame: Weeks 2, 4, 8, 12 and 18

Double Blind Phase: Percentage of Participants With JADAS-27 CRP Minimum Disease Activity at Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36, 40 and 44

Minimum Disease Activity is defined by a JADAS-27 CRP score less than or equal to 3.8 for participants with polyarthritis, and less than or equal to 2 for participants with oligoarthritis. JADAS-27 is a validated composite disease activity measure for JIA. JADAS-27 CRP score was derived from four components; 1) Physician global assessment of disease activity (assessed on a VAS of 0 \[no activity\] to 10 \[maximum activity\]), 2) Parent/legal guardian/subject global assessment of overall well-being (assessed on a VAS of 0 \[very well\] to 10 \[very poor\]), 3) Number of joints with active disease (maximum of 27 and defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness), 4) CRP (measured in milligram per liter \[mg/L\] and value normalized to 0 to 10 scale). The overall JADAS-27 score ranges from 0-57. A higher score indicates more disease activity.

Time frame: Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36, 40 and 44

Open-Label Phase: Percentage of Participants With JADAS-27 CRP Inactive Disease Activity at Week 2, 4, 8, 12 and 18

JADAS-27 inactive disease is defined by a JADAS score less than or equal to 1. JADAS-27 Inactive Disease cutoff values are defined as: 1) Polyarthritis: Inactive Disease: \<=1 and 2) Oligoarthritis (\<4 active joints): Inactive Disease: \<=1. JADAS-27 is a validated composite disease activity measure for JIA. JADAS-27 CRP score was derived from four components; 1) Physician global assessment of disease activity (assessed on a VAS of 0 \[no activity\] to 10 \[maximum activity\]), 2) Parent/legal guardian/subject global assessment of overall well-being (assessed on a VAS of 0 \[very well\] to 10 \[very poor\]), 3) Number of joints with active disease (maximum of 27 and defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness), 4) CRP (measured in milligram per liter \[mg/L\] and value normalized to 0 to 10 scale). The overall JADAS-27 score ranges from 0-57. A higher score indicates more disease activity.

Time frame: Weeks 2, 4, 8, 12 and 18

Double Blind Phase: Percentage of Participants With JADAS-27 CRP Inactive Disease Activity at Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36, 40 and 44

Time frame: Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36, 40 and 44

Double Blind Phase: Percentage of Participants With JIA ACR Inactive Disease at Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

JIA ACR Inactive Disease criteria included: No joints with active arthritis, No fever, rash, serositis, splenomegaly, hepatomegaly, or generalized lymphadenopathy attributable to sJIA, No active uveitis (as defined by the Standardized Uveitis Nomenclature (SUN) Working Group), Normal ESR (within normal limits of the method used where tested) or, if elevated, not attributable to JIA, Physician global assessment of disease activity (assessed on a VAS of 0 \[no activity\] to 10 \[maximum activity\]) score of 'best possible' (score of "0") on the scale used, morning stiffness of \<=15 minutes.

Time frame: Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Double Blind Phase: Percentage of Participants With Presence of JIA ACR Clinical Remission

JIA ACR Clinical Remission Criteria included: Clinical inactive disease for 6 months continuously while on medications for JIA. Clinical Inactive Disease criteria included: No joints with active arthritis, No fever, rash, serositis, splenomegaly, hepatomegaly, or generalized lymphadenopathy attributable to sJIA, No active uveitis (as defined by the SUN Working Group), Normal ESR (within normal limits of the method used where tested) or, if elevated, not attributable to JIA, Physician global assessment of disease activity (assessed on a VAS of 0 \[no activity\] to 10 \[maximum activity\]) score of 'best possible' (score of "0") on the scale used, morning stiffness of less than or equal to (\<=) 15 minutes.

Time frame: From Week 18 in double blind phase up to Week 44

Open Label Phase: JIA ACR Core Variable- Change From Baseline in Number of Joints With Active Arthritis at Week 2, 4, 8, 12 and 18

Number of joints with active arthritis defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness. The score range of the number of joints is from 0-71.

Time frame: Baseline, Weeks 2, 4, 8, 12 and 18

Double Blind Phase: JIA ACR Core Variable- Change From Double-Blind Baseline in Number of Joints With Active Arthritis at Weeks 20, 24, 28, 32, 36, 40 and 44

Number of joints with active arthritis defined as joint with swelling or, in absence of swelling, limited range of motion accompanied by either pain on motion or tenderness. Number of joints ranged from 0 to 71.

Time frame: Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Open Label Phase: JIA ACR Core Variable- Change From Baseline in Number of Joints With Limited Range of Motion at Weeks 2, 4, 8, 12 and 18

The maximum number of joints with limitation of movement was 67 and these were defined as those in the joint assessment with 'limitation of motion'.

Time frame: Baseline, Weeks 2, 4, 8, 12 and 18

Double Blind Phase: JIA ACR Core Variable- Change From Double-Blind Baseline in Number of Joints With Limited Range of Motion at Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36, 40 and 44

The maximum number of joints with limitation of movement was 67 and these were defined as those in the joint assessment with 'limitation of motion'.

Time frame: Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Open Label Phase: JIA ACR Core Variable- Change From Baseline in Physician Global Evaluation of Disease Activity at Week 2, 4, 8, 12 and 18

Physician global evaluation of disease activity was measured on a 21-numbered circle VAS ranges from 0 to 10 (in 0.5 increments), with '0' as 'No Activity' and '10' as 'Maximum Activity', higher score indicated more disease activity.

Time frame: Baseline, Weeks 2, 4, 8, 12 and 18

Double Blind Phase: JIA ACR Core Variable- Change From Double-Blind Baseline in Physician Global Evaluation of Disease Activity at Weeks 20, 24, 28, 32, 36, 40 and 44

Time frame: Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Open Label Phase: JIA ACR Core Variable- Change From Baseline in Parent/Legal Guardian/Participant Global Evaluation of Overall Well-Being at Weeks 2, 4, 8, 12 and 18

The parent/or legal guardian/participant rated the overall well-being on a 21-numbered circle VAS ranges from 0 to 10 (in 0.5 increments), with '0' as 'Very Well' and '10' as 'Very Poorly', higher scores=more disease activity.

Time frame: Baseline, Weeks 2, 4, 8, 12 and 18

Double Blind Phase: JIA ACR Core Variable- Change From Double-Blind Baseline in Parent/Legal Guardian/Participant Global Evaluation of Overall Well-Being at Weeks 20, 24, 28, 32, 36, 40 and 44

Time frame: Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Open Label Phase: JIA ACR Core Variable- Change From Baseline in Childhood Health Assessment Questionnaire- Disability Index (CHAQ-DI) Total Scores at Weeks 2, 4, 8, 12 and 18

CHAQ is a valid assessment of functional disability, discomfort in participants with rheumatic diseases. It comprises of three indices: Disability and Discomfort, and global assessment of arthritis (overall well-being). CHAQ-DI: as a measure of functional ability, consists of 30 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities-distributed, among a total of 30 items. Each question was rated on a 4-point scale of difficulty in performance ranges from 0 (no difficulty) to 3 (unable to do). To calculate the overall score, the participant must have a domain score in at least 6 of the 8 domains. Scores of 8 domains were averaged to calculate the CHAQ-DI total score which ranges from 0 (no or minimal physical dysfunction) to 3 (very severe physical dysfunction), higher score indicates more disability. Change from baseline at Weeks 2, 4, 8, 12 and 18 in DI total score is reported.

Time frame: Baseline, Weeks 2, 4, 8, 12 and 18

Double Blind Phase: JIA ACR Core Variable- Change From Double-Blind Baseline in Childhood Health Assessment Questionnaire- Disability Index (CHAQ-DI) Total Scores at Weeks 20, 24, 28, 32, 36, and 40

CHAQ: valid assessment of functional disability, discomfort in participants with rheumatic diseases. It comprises of three indices: Disability and Discomfort, and global assessment of arthritis (overall well-being). CHAQ-DI: as a measure of functional ability, consists of 30 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities-distributed, among a total of 30 items. Each question was rated on a 4-point scale of difficulty in performance ranges from 0 (no difficulty) to 3 (unable to do). To calculate overall score, participant must have a domain score in at least 6 of the 8 domains. Scores of 8 domains were averaged to calculate the CHAQ-DI total score which ranges from 0 (no or minimal physical dysfunction) to 3 (very severe physical dysfunction), higher score indicates more disability. Change from double-blind baseline at Weeks 20, 24, 28, 32, 36, and 40 in DI total score is reported.

Time frame: Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, and 40

Open-Label Phase: Change From Baseline in Child Health Questionnaire (CHQ) Responses at Week 4 and Week 18

CHQ: 50-item, 14 subscale (Global health, physical functioning, social limitations: emotional, social limitations: physical, bodily pain, behavior, global behavior, mental health, self-esteem, general health, Change in health, emotional impact on parent, time impact on parent, family activities, family cohesion) parent or legal guardian assessed instrument of child's physical, emotional, social well-being, and relative burden of disease on the parents. Each subscale rated on Likert-type scale: range 0 to 100; higher scores indicate a more positive health status. Two summary scores: Physical Health and Psychosocial Health were weighted composites derived from subscale items using scoring algorithms (transformed scores); range 0 to 100: higher scores indicate more positive health status.

Time frame: Baseline, Week 4 and Week 18

Double Blind Phase: Change From Double-Blind Baseline in Child Health Questionnaire (CHQ) Responses at Week 44

Time frame: Double-Blind Baseline (Week 18), Week 44

Open Label Phase: Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ)- Discomfort Index at Weeks 2, 4, 8, 12 and 18

CHAQ is a validated instrument and comprises of two indices, Disability and Discomfort, and global assessment of arthritis (overall well-being). Discomfort Index included: assessment of discomfort, the parent/legal guardian/participant were asked to provide a response to the question: How much pain do you think your child had because of his or her illness in the past week?, The parent/legal guardian/ participant rated the overall pain on a 0 to 10 VAS, where '0' indicates 'No Pain' and '10' indicates 'Very Severe Pain', higher scores indicates more severity.

Time frame: Baseline, Weeks 2, 4, 8, 12 and 18

Double Blind Phase:Change From Double-Blind Baseline in Childhood Health Assessment Questionnaire (CHAQ)- Discomfort Index at Weeks 20, 24, 28, 32, 36, 40 and 44

Time frame: Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36,40 and 44

Open-Label Phase: Percentage of Participants With Active Uveitis at Baseline

Uveitis is the inflammation of the uvea. Participants were assessed for presence of uveitis (according to Standard Uveitis Nomenclature \[SUN\]). If Uveitis was present in participant at Baseline, it was considered as "active uveitis"; If Uveitis was not present in participant at Baseline, it was considered as "Inactive uveitis". As per SUN, Uveitis is defined as: anterior (in which anterior chamber is primary site of inflammation); intermediate (primary site of inflammation: vitreous); posterior (primary site of inflammation: retina or choroid). Percentage of participants with active uveitis (of any type) are reported.

Time frame: Baseline

Double Blind Phase: Percentage of Participants With Active Uveitis at Week 24 and Week 44

Time frame: Week 24 and Week 44

Open-Label Phase: Change From Baseline in the Tender Entheseal Assessment at Weeks 2, 4, 8, 12 and 18

Participants with enthesitis-related arthritis (ERA) undergo Tender entheseal assessment. Tender entheseal assessment: Entheses were assessed and coded as: 1= any tenderness, 0= no tenderness, NE= not evaluable. Total number of tender entheses: 66\*(total number of tender entheses with counts \> 0)/number of non-missing tender entheses. If \> 33 tender entheseal counts were missing, total number of tender entheses was defined as missing.

Time frame: Baseline, weeks 2, 4, 8, 12 and 18

Double Blind Phase: Change From Double-Blind Baseline in the Tender Entheseal Assessment at Weeks 20, 24, 28, 32, 36, 40 and 44

Participants with ERA undergo Tender entheseal assessment. Tender entheseal assessment: Entheses were assessed and coded as: 1= any tenderness, 0= no tenderness, NE= not evaluable. Total number of tender entheses: 66\*(total number of tender entheses with counts \> 0)/number of non-missing tender entheses. If \> 33 tender entheseal counts were missing, total number of tender entheses was defined as missing.

Time frame: Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Open-Label Phase: Change From Baseline in the Modified Schober's Test at Week 2, 4, 8, 12 and 18

Participants with ERA undergo Modified Schober's Test. In the Modified Schober's Test, a mark was placed 5 cm below the midpoint of a line that joined the posterior superior iliac spines. Another mark was placed 10 cm above the first. The participant then bent maximally forward with the knees fully extended. The distance between the two marks was then re-measured. The full measurement between the two lines was recorded to the nearest tenth of a centimeter and is reported.

Time frame: Baseline, Weeks 2, 4, 8, 12 and 18

Double Blind Phase: Change From Double Blind Baseline in the Modified Schober's Test at Week 20, 24, 28, 32, 36, 40 and 44

Time frame: Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Open-Label Phase: Change From Baseline in the Overall Back Pain and Nocturnal Back Pain Responses at Week 2, 4, 8, 12 and 18

Participants with ERA undergo Overall Back Pain and Nocturnal Back Pain assessment. For Overall Back Pain, parent/legal guardian/participant were asked to provide a response to the question: What is the amount of back pain at any time that your child experienced in the past week? And For Nocturnal Back Pain: What is the amount of back pain at night that your child experienced in the past week?. Response to these questions was provided by parent/legal guardian/participant using a VAS of 0-10, where 0= No Pain and 10= Most Severe Pain, higher score indicated more severe pain.

Time frame: Baseline, Weeks 2, 4, 8, 12 and 18

Double Blind Phase: Change From Double-Blind Baseline in the Overall Back Pain and Nocturnal Back Pain Responses at Week 20, 24, 28, 32, 36, 40 and 44

Time frame: Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Open-Label Phase: Changes From Baseline in Percentage of Body Surface Area (BSA) Affected With Psoriasis at Weeks 2, 4, 8, 12 and 18

Percentage of body surface area affected by psoriasis was estimated using the palm method. One of the participant's palm to proximal interphalangeal (PIP) and thumb =\\together represented 1% of total BSA. Regions of the body were assigned specific number of palms with percentage (Head and Neck = 10% \[10 palms\], Upper extremities = 20% \[20 palms\], Trunk \[axillae and groin\] = 30% \[30 palms\], Lower extremities \[buttocks\] = 40% \[40 palms\]). The number of palms of psoriatic skin in a body region was used to determine the extent (%) to which a body region was involved with psoriasis. The total BSA affected was the summation of individual regions affected.

Time frame: Baseline, Weeks 2, 4, 8, 12 and 18

Double Blind Phase: Changes From Double Blind Baseline in Body Surface Area (BSA) Affected With Psoriasis at Week 20, 24, 28, 32, 36, 40 and 44

Percentage of body surface area affected by psoriasis was estimated using the palm method. One of the participant's palm to PIP and thumb together represented 1% of total BSA. Regions of the body were assigned specific number of palms with percentage (Head and Neck = 10% \[10 palms\], Upper extremities = 20% \[20 palms\], Trunk \[axillae and groin\] = 30% \[30 palms\], Lower extremities \[buttocks\] = 40% \[40 palms\]). The number of palms of psoriatic skin in a body region was used to determine the extent (%) to which a body region was involved with psoriasis. The total BSA affected was the summation of individual regions affected.

Time frame: Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Open-Label Phase: Changes From Baseline in Physician's Global Assessment (PGA) of Psoriasis Assessments at Weeks 2, 4, 8, 12 and 18

The PGA of psoriasis was scored on a 6-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 (0 \[no symptom\] to 5 \[severe symptom\]). The total score was calculated as average of the 3 severity scores and rounded to the nearest whole number score to determine the PGA score and ranged as 0= no symptom to 5=severe, higher score indicates more severity.

Time frame: Baseline, Weeks 2, 4, 8, 12 and 18

Double Blind Phase:Change From Double-Blind Baseline in Physician's Global Assessment (PGA) of Psoriasis Assessments at Weeks 20, 24, 28, 32, 36, 40 and 44

Time frame: Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Open-Label Phase: Taste Assessment of Tofacitinib Oral Solution on Day 14

Oral solution was given only to participants weighing \<40 kg and to the participants who were unable to swallow tablets. Taste assessment was evaluated using a 5 categories questionnaire. Participants were asked to answer in one of the following categories to describe the taste of oral solution of tofacitinib: dislike very much, dislike a little, not sure, like a little and like very much. Number of participants within each category are reported.

Time frame: Day 14

Open-Label Phase: Number of Participants With Serious Infections, Cytopenia, Malignancies and Cardiovascular Diseases

Serious infection defined as any infection that requires hospitalization for treatment or requires parenteral antimicrobial therapy or meets other criteria that require it to be classified as a serious adverse event. Cytopenia was categorized as: lymphocyte counts: \<500 lymphocytes/ millimeter\^3 (mm), neutrophil counts \<1000 neutrophils/mm\^3, platelet counts \<100,000 platelets/mm\^3, any single hemoglobin value \<8 grams/decilitre (g/dL) and any single hemoglobin value drops \>=2 g/dL below baseline. Number of Participants With serious infections, cytopenia, malignancies and Cardiovascular Diseases are reported.

Time frame: From the first dose of study drug up to Week 18

Double Blind Phase: Number of Participants With Serious Infections, Cytopenia, Malignancies and Cardiovascular Diseases

Serious infection defined as any infection that requires hospitalization for treatment or requires parenteral antimicrobial therapy or meets other criteria that require it to be classified as a serious adverse event. Cytopenia was categorized as: lymphocyte counts \<500 lymphocytes/mm\^3, neutrophil counts \<1000 neutrophils/mm\^3, platelet counts \<100000 platelets/mm\^3, any single hemoglobin (hg) value \<8 g/dL and any single hemoglobin value drops \>=2 g/dL below baseline. Number of Participants With serious infections, cytopenia, malignancies and Cardiovascular Diseases are reported.

Time frame: From the first dose of study drug in double blind up to week 44

Open-Label Phase: Number of Participants With Tanner Staging Evaluation (Pubic Hair)

Tanner stage is a scale used to document the stage of development of puberty by assessing the secondary sexual characteristics: Pubic hair (both male and female), breast size (for females); and size of the genitalia (for males).were assessed in this study and with values in the scale ranging from: Stage 1: no hair, Stage 2: downy hair, Stage 3: Scant terminal hair, Stage 4: Terminal hair that fills the entire triangle overlying the pubic region and Stage 5: Terminal hair that extends beyond the inguinal crease onto the thigh. Tanner Stage for pubic hair at Day 1 was summarized and reported using number of participants in each stage.

Time frame: Day 1

Double Blind Phase: Number of Participants With Tanner Staging Evaluation (Pubic Hair)

Tanner stage is a scale used to document the stage of development of puberty by assessing the secondary sexual characteristics: Pubic hair (both male and female), breast size (for females); and size of the genitalia (for males) were assessed in this study and with values in the scale ranging from: Stage 1: no hair, Stage 2: downy hair, Stage 3: Scant terminal hair, Stage 4: Terminal hair that fills the entire triangle overlying the pubic region and Stage 5: Terminal hair that extends beyond the inguinal crease onto the thigh. Tanner Stage for pubic hair at Week 44 was summarized and reported using number of participants in each stage.

Time frame: Week 44

Open-Label Phase: Number of Participants With Tanner Staging Evaluation (Breast Exam)

Tanner stage is a scale used to document the stage of development of puberty by assessing the secondary sexual characteristics: Pubic hair (both male and female), breast size (for females); and size of the genitalia (for males).were assessed in this study and with values in the scale ranging from: Stage 1: No glandular breast tissue palpable, Stage 2: Breast bud palpable under areola (1st pubertal sign in females), Stage 3: Breast tissue palpable outside areola; no areolar development, Stage 4: Areola elevated above contour of the breast, forming "double scoop" appearance, Stage 5: Areolar mound recedes back into single breast contour with areolar hyperpigmentation, papillae development and nipple protrusion. Tanner Stage for Breast at Day 1 was summarized and reported using number of participants in each stage.

Time frame: Day 1

Double Blind Phase: Number of Participants With Tanner Staging Evaluation (Breast Exam)

Tanner stage is a scale used to document the stage of development of puberty by assessing the secondary sexual characteristics: Pubic hair (both male and female), breast size (for females); and size of the genitalia (for males).were assessed in this study and with values in the scale ranging from: Stage 1: No glandular breast tissue palpable, Stage 2: Breast bud palpable under areola (1st pubertal sign in females), Stage 3: Breast tissue palpable outside areola; no areolar development, Stage 4: Areola elevated above contour of the breast, forming "double scoop" appearance, Stage 5: Areolar mound recedes back into single breast contour with areolar hyperpigmentation, papillae development and nipple protrusion. Tanner Stage for Breast at Week 44 was summarized and reported using number of participants in each stage.

Time frame: Week 44

Open-Label Phase: Number of Participants With Tanner Staging Evaluation (Genitalia)

Tanner stage is a scale used to document the stage of development of puberty by assessing the secondary sexual characteristics: Pubic hair (both male and female), breast size (for females); and size of the genitalia (for males).were assessed in this study and with values in the scale ranging from: Stage 1: Testicular volume \< 4 ml or long axis \< 2.5 cm, Stage 2: 4 ml-8 ml (or 2.5-3.3 cm long), 1st pubertal sign in males, Stage 3: 9 ml-12 ml (or 3.4-4.0 cm long), Stage 4: 15-20 ml (or 4.1-4.5 cm long), Stage 5: \> 20 ml (or \> 4.5 cm long). Tanner Stage for genitalia at Day 1 was summarized and reported using number of participants in each stage.

Time frame: Day 1

Double Blind Phase: Number of Participants With Tanner Staging Evaluation (Genitalia)

Tanner stage is a scale used to document the stage of development of puberty by assessing the secondary sexual characteristics: Pubic hair (both male and female), breast size (for females); and size of the genitalia (for males).were assessed in this study and with values in the scale ranging from: Stage 1: Testicular volume \< 4 ml or long axis \< 2.5 cm, Stage 2: 4 ml-8 ml (or 2.5-3.3 cm long), 1st pubertal sign in males, Stage 3: 9 ml-12 ml (or 3.4-4.0 cm long), Stage 4: 15-20 ml (or 4.1-4.5 cm long), Stage 5: \> 20 ml (or \> 4.5 cm long). Tanner Stage for genitalia at Week 44 was summarized and reported using number of participants in each stage.

Time frame: Week 44

Open-Label Phase: Number of Participants With Laboratory Abnormalities

Criteria: Hemoglobin(Hg),hematocrit erythrocytes(Ery); \<0.8\*lower limit of normal (LLN), Ery. Mean Corpuscular Volume; \<0.9\*LLN, \>1.1\*upper limit of normal (ULN), Platelets; \<0.5\*LLN, \>1.75\*ULN, Leukocytes (leu); \<0.6\*LLN, \>1.5\*ULN, Lymphocytes (Ly), Ly/leu, Neutrophils, Neutrophils/leu \<0.8\*LLN, Basophils/leu, Eosinophils, Eosinophils/leu, Monocytes, Monocytes/leu \>1.2\*ULN, Ery Sedimentation Rate \>1.5\*ULN. Bilirubin, Indirect Bilirubin \>1.5\*ULN, AST, ALT, Gamma Glutamyl Transferase, Alkaline Phosphatase \>3.0\*ULN, Albumin \>1.2\*ULN, Creatinine \>1.3\*ULN, HDL Cholesterol (Chol)\<0.8\*LLN, LDL Chol, LDL Chol Friedewald Est PEG \>1.2\*ULN, Triglycerides \>1.3\*ULN, Calcium \<0.9\*LLN, Bicarbonate \<0.9\*LLN, Glucose \>1.5\*ULN, Creatine Kinase \>2.0\*ULN, C Reactive Protein \>1.1\*ULN, Chol \>1.3\*ULN. Urinalysis: Specific Gravity \>1.030, Glucose, Ketones, Protein, Hg, Nitrite, Leu Esterase \>=1, Ery, Leu \>=20, Hyaline Casts \>1.Only those category in which at least 1 participant had data is reported.

Time frame: From the first dose of study drug up to Week 18

Double Blind Phase: Number of Participants With Laboratory Abnormalities

Criteria: Hg, hematocrit Ery; \<0.8\* LLN, Ery. Mean Corpuscular Volume; \<0.9\*LLN, \>1.1\* ULN, Platelets; \<0.5\*LLN, \>1.75\*ULN, leu; \<0.6\*LLN, \>1.5\*ULN, Ly, Ly/leu, Neutrophils, Neutrophils/leu \<0.8\*LLN, Basophils/leu, Eosinophils, Eosinophils/leu, Monocytes, Monocytes/leu \>1.2\*ULN, Prothrombin Time \>1.1\*ULN, Ery Sedimentation Rate \>1.5\*ULN. Bilirubin, Direct Bilirubin, Indirect Bilirubin \>1.5\*ULN, AST, ALT, Gamma Glutamyl Transferase (GGT), Alkaline Phosphatase \>3.0\*ULN, Albumin \>1.2\*ULN, Creatinine \>1.3\*ULN, HDL Cholesterol (Chol)\<0.8\*LLN, LDL Chol, LDL Chol Friedewald Est PEG \>1.2\*ULN, Triglycerides \>1.3\*ULN, Calcium \<0.9\*LLN, Bicarbonate \<0.9\*LLN, Glucose \>1.5\*ULN, Creatine Kinase \>2.0\*ULN, C Reactive Protein \>1.1\*ULN, Chol \>1.3\*ULN. Urinalysis: Specific Gravity \>1.030, pH \>8, urine Glucose, Ketones, Protein, Hg, Nitrite, Leu Esterase \>=1, Ery, Leu \>=20, Hyaline Casts \>1.Only those category in which at least 1 participant had data is reported.

Time frame: From the first dose of study drug in double blind up to Week 44

Open-Label Phase: Number of Participants With Physical Examination Abnormalities

Physical examination included: abdomen, ears, extremities, eyes, general appearance, head, heart, lungs, lymph nodes, neurological, nose, skin, and throat. Abnormality in physical examination was based on investigator's discretion.

Time frame: Baseline, Weeks 2, 4, 8, 12 and 18

Double Blind Phase: Number of Participants With Physical Examination Abnormalities

Time frame: Weeks 18, 20, 24, 28, 32, 36, 40 and 44

Open-Label Phase: Number of Participants With Vital Sign Abnormalities

Vital Sign Abnormalities criteria included: sitting diastolic blood pressure millimeters of Mercury (mmHG) of \<50 mmHg, sitting pulse rate beats per minute (bpm) of \<40 or 120 bpm, sitting systolic blood pressure (mmHG) of \<90 mmHg, supine diastolic blood pressure (mmHG) of \<50 mmHg, supine pulse rate (BPM) of \<40 bpm or \>120 bpm, supine systolic blood pressure (mmHG) of 90 mmHg.

Time frame: From the first dose of study drug up to Week 18

Double Blind Phase: Number of Participants With Vital Sign Abnormalities

Vital Sign Abnormalities criteria included: diastolic blood pressure (mmHG) of \<50 mmHg, Pulse rate (BPM) of \<40 bpm or \>120 bpm, sitting diastolic blood pressure (mmHG) of \<50 mmHg, sitting pulse rate beats per minute (bpm) of \<40 bpm or \>120 bpm, sitting systolic blood pressure (mmHG) of \<90 mmHg, supine diastolic blood pressure (mmHG) of \<50 mmHg, supine pulse rate (BPM) of \<40 bpm or \>120 bpm, supine systolic blood pressure (mmHG) of \<90 mmHg, systolic blood pressure (mmHG) of \<90 mmHg.

Time frame: From the first dose of study drug in double blind up to week 44

Open-Label Phase: Number of Participants With Change From Baseline in Vital Sign Measures

Change in vital Signs included: Sitting diastolic blood pressure \[mmHG\]: \>=20mmHg increase from baseline (IFB) and \>= 20mmHg decrease from baseline (DFB). Sitting systolic blood pressure mmHG: \>= 30mmHg IFB and \>= 30mmHg DFB. Supine diastolic blood pressure mmHG: \>= 20mmHg IFB and \>= 20mmHg DFB. Supine systolic blood pressure mmHG: \>= 30mmHg IFB and \>= 30mmHg DFB.

Time frame: From the first dose of study drug up to Week 18

Double Blind Phase: Number of Participants With Change From Baseline in Vital Sign Measures

Change in vital Signs included: Sitting diastolic blood pressure (mmHG): \>=20mmHg IFB and \>= 20mmHg DFB. Sitting systolic blood pressure mmHG: \>= 30mmHg IFB and \>= 30mmHg DFB. Supine diastolic blood pressure mmHG: \>= 20mmHg IFB and \>= 20mmHg DFB. Supine systolic blood pressure mmHG: \>= 30mmHg IFB and \>= 30mmHg DFB.

Time frame: From the first dose of study drug in double blind up to week 44