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A Study of Tocilizumab in Patients With Active Polyarticular Juvenile Idiopathic Arthritis

Primary Purpose

Juvenile Idiopathic Arthritis

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Tocilizumab

Placebo

About this trial

This is an interventional treatment trial for Juvenile Idiopathic Arthritis

Eligibility Criteria

2 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Children/juveniles, 2-17 years of age.
Polyarticular-course juvenile idiopathic arthritis (pcJIA) ≥ 6 months duration.
Active disease (≥ 5 active joints, ≥ 3 with limitation of motion).
Inadequate response to or inability to tolerate methotrexate.
Methotrexate, oral corticosteroids, and non-steroidal anti-inflammatory drugs (NSAID) at stable dose(at least 8, 4, and 2 weeks,respectively) prior to baseline.
Biologics discontinued, between at least 1 and 20 weeks prior to baseline, depending on biologic.

Exclusion Criteria:

Auto-immune, rheumatic disease or overlap syndrome other than pcJIA.
Wheelchair bound or bedridden.
Intra-articular, intramuscular, intravenous, or long-acting corticosteroids within 4 weeks prior to baseline.
Disease-modifying anti-rheumatic drugs (DMARD) (other than methotrexate) within 4 weeks prior to baseline.
Previous treatment with tocilizumab.

Sites / Locations

Connecticut Children's Medical Center; 5E Clinical Trials Unit
Children's National Medical Center; Pediatric Rheumatology
Delray Research Associates
Miami Children's Hospital
The University of Chicago;Department of Pediatrics
University of Louisville Research Foundation, Inc; Kosair Charities Pediatric Clinical Research Unit
Children's Hospital
Hackensack University Medical Center; Pediatric Rheumatology
Cincinnati Children'S Hospital Medical Center; Division of Rheumatology
Healthcare Research Consultants
Hospital Gral de Niños Pedro Elizalde
Hospital de Niños; Reumatologia
Caici; Rheumatology
Centro Medico Privado de Reumatologia; Reumathology
Westmead Hospital; Paediatric Rheumatology
Royal Children'S Hospital; Paediatric Rheumatology
Princess Margaret Children'S Hospital; Department of Immunology
UZ Gent
UZ Leuven Gasthuisberg
Hospital Universitario Pedro Ernesto; Nucleo de Estudos da Saude do Adolescente
Instituto de Puericultura E Pediatria Martagão Gesteira
Hospital das Clinicas - UFRGS
Hospital das Clinicas - FMUSP; Instituto da Crianca - Reumatologia
Alberta Children'S Hospital
British Columbia Children's Hospital; Rheumatology
Children'S Hospital of Eastern Ontario
Hospital For Sick Children
Hôpital Pellegrin; Urgences Pédiatriques
CH de Bicêtre; Pediatrie Generale
Hôpital Lapeyronie; Immuno-Rhumatologie Pr Jorgensen
Hopital Cochin; Rhumatologie A
Hop Necker Enfants Malades;UIH
Hopitaux De Brabois; Medecine Infantile II
Charité Campus; Virchow Klinikum Berlin
Klinik Bremen-Mitte; Prof. Hess-Kinderklinik
Clementine Hospital; Kinder- und Jugendrheumatologie
Asklepios Klinik; Zentrum fuer Allgemeine Paediatrie und Neonatologie
Irccs Ospedale Pediatrico Bambin Gesu - Dip. Di Medicina
IRCCS G. Gaslini; Pediatria II
ASST CENTRO SPECIALISTICO ORTOPEDICO TRAUMATO-LOGICO GAETANO PINI/CTO; Reumatol. Pediatrica
Nuovo Ospedale Pediatrico Meyer; Reumatologia - Clinica Pediatrica 1°
Univ. Di Padova - Dip. Di Pediatria - Unita' Reumatol. Pediatrica
Cif Biotec Medica Sur
Inst. Mexicano de Investigacion Clinica
Cliditer SA de CV
Hospital Universitario Dr. Jose Eleuterio Gonzalez; Pediatria
Clinica San Felipe; Consultorio de Reumatología
Clinica San Borja; Servicio De Reumatologia
Instituto Nacional De Salud Del Niño
Wojewodzki Szpital Dzieciecy Im. J. Brudzinskiego
Wojewodzki Specjalistyczny Szpital Dzieciecy Sw Ludwika; Oddzial Dzieci Starszych
Uniwersytecki Szpital Kliniczny Nr 4 im. M. Konopnickiej; Oddz. Kardiolog. i Reumatolog. dla Dzieci
Dzieciecy Szpital Kliniczny IM. Prof. A. Gebali; Oddzial Pediatrii Chorob Pluc I Reumatologii
Centrum Pediatrii im Jana Pawla II; Oddzial Reumatologiczny
Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im. Prof. Eleonory Reicher
FSBI "Scientific Research Institute of Rheumatology" of russian Academy of Medical Sciences
SI Sceintific children health center RAMS
I. M. Sechenov Moscow State Medical University; The Ministry of Health and Social Development of RF
Southern District Medical Center of Roszdrav
Saint-Petersburg State; Pediatrics Medical Academy
Samara Regional Clinical Cardiology Dispensary
Hospital Universitario Reina Sofia; Servicio de Reumatologia
Hospital General Universitario Gregorio Marañon; Servicio de Reumatología
Hospital Ramon y Cajal ; Servicio de Reumatologia
Hospital Universitario Virgen Macarena; Servicio de Reumatologia
Hospital Universitario la Fe: Servicio de Reumatologia Pediatrica
Bristol Royal Hospital For Children
Royal Liverpool Childrens Hospital; Rheumatology
Great Ormond Street Hospital for Sick Children; Institute of Child Health

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Arm Label

Tocilizumab 10 mg/kg in patients weighing < 30 kg

Tocilizumab 8 mg/kg in patients weighing < 30 kg

Tocilizumab 8 mg/kg in patients weighing ≥ 30 kg

Placebo

Arm Description

Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.

Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.

Patients received placebo to tocilizumab intravenously every 4 weeks.

Outcomes

Primary Outcome Measures

Percent of Patients With a Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30 (ACR30) Flare in Part II of the Study (Weeks 16-40)

JIA ACR30 flare is defined as a ≥ 30% worsening of 3 of 6 variables and no more than 1 of the remaining variables improving > 30%. The 6 variables are physician global assessment of disease activity (worsening of 20 units minimum on a 0-100 visual analog scale [VAS]), parent/patient global assessment of overall well-being (worsening of 20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0[best]-3[worst]). Patients who withdrew or who took escape medication are classified as flared. The analysis used the Cochran-Mantel-Haenszel test with the stratification variables background use of methotrexate and oral corticosteroids applied at Week 16.

Secondary Outcome Measures

Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses in Part I of the Study (Baseline to Week 16)

A JIA ACR30/50/70/90 response is defined as a ≥ 30/50/70/90% response on 3 of 6 variables and no more than 1 of the remaining variables worsening > 30%. The 6 variables are physician global assessment of disease activity (20 units minimum on a 0-100 visual analog scale [VAS]), parent/patient global assessment of overall well-being (20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0[best]-3[worst]).

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Physician Global Assessment of Disease Activity at the End of Part I of the Study (Week 16)

The patient's treating physician provides a rating of the patient's arthritis disease activity on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'arthritis inactive' (ie, symptom-free and no arthritis symptoms) and the extreme right end represents 'arthritis very active'. A higher score indicates more disease activity. A negative change score indicates improvement.

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Patient/Parent Global Assessment of Overall Well-being at the End of Part I of the Study (Week 16)

The patient or parent/guardian, as appropriate, provides a rating of the patient's well-being on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'very well' (ie, symptom-free and no arthritis disease activity) and the extreme right end represents 'very poor' (ie, maximum arthritis disease activity). A higher score indicates poorer well-being. A negative change score indicates improvement.

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Active Arthritis at the End of Part I of the Study (Week 16)

Joints with active arthritis are defined as joints with swelling present or pain present and limitation of motion. The maximum number of joints with active arthritis is 71. The joint assessment is performed by an independent assessor who is not the treating physician and who is blinded to all other aspects of the patient's efficacy and safety data. A negative change score indicates improvement.

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Limitation of Movement at the End of Part I of the Study (Week 16)

Joints with limitation of movement are defined as joints with limitation of motion. The maximum number of joints with limitation of movement is 67. The joint assessment is performed by an independent assessor who is not the treating physician and who is blinded to all other aspects of the patient's efficacy and safety data. A negative change score indicates improvement.

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Erythrocyte Sedimentation Rate (ESR) at the End of Part I of the Study (Week 16)

Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory. A negative change score indicates improvement.

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Functional Ability at the End of Part I of the Study (Week 16)

Functional ability is assessed with the Childhood Health Assessment Questionnaire (CHAQ-DI) disability index which consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. There are 4 possible responses to each question (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). A domain score is the highest score in that domain. If aids and devices listed in the questionnaire or assistance from a person are required to perform a task, a domain score of 0 or 1 is increased to 2; if the domain score is 2 or 3, the domain score is not adjusted. To calculate the overall score, the patient must have a domain score in at least 6 of the 8 domains. The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A higher score indicates less ability. A negative change score indicates improvement.

Juvenile Arthritis Disease Activity Score (JADAS-27) at the End of Part I of the Study (Week 16)

The JADAS-27 is derived from the following components: Physician's global assessment of disease activity on a 0-100 mm visual analog scale (VAS)/10, patient/parent's global assessment of overall well-being on a 0-100 mm VAS/10, normalized erythrocyte sedimentation rate (ESR) (if ESR is ≤ 20 then set to 0, if ≥ 120 then set to 10, and if > 20 and < 120 then apply formula [ESR-20]/10), and number of joints (maximum of 27) with active arthritis (cervical spine, left/right elbow, left/right wrist, left/right MCP1-3, left/right PIP1-5, left/right hips, left/right knee and left/right ankle). The scores for the first 3 components range from 0-10; the score for the final component ranges from 0-27. The overall JADAS-27 score ranges from 0-57. A higher score indicates more disease activity.

Pain Visual Analogue Scale (VAS) Score at the End of Part I of the Study (Week 16)

Percent of Patients With Inactive Disease at the End of Part I of the Study (Week 16)

A patient is judged to have inactive disease if all of the following criteria are met: Number of joints with active arthritis = 0; absence of active uveitis, defined by the adverse event preferred terms 'uveitis' and 'intermediate uveitis'; normal erythrocyte sedimentation rate (< 20 mm/hour regardless of age and sex); and physician's global assessment of overall well-being visual analog scale score ≤ 10.

Percent of Patients With an Elevated C-reactive Protein Concentration at Baseline That Had Normalized at the End of Part I of the Study (Week 16)

C-reactive protein (CRP), an acute phase protein, was measured in blood samples with a high-sensitivity CRP (hs-CRP) test using laser nephelometry.

Percent of Patients With an Elevated Erythrocyte Sedimentation Rate at Baseline That Had Normalized at the End of Part I of the Study (Week 16)

Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory.

Percent of Patients With an Elevated Platelet Count at Baseline That Had Normalized at the End of Part I of the Study (Week 16)

Platelets were measured in blood samples taken from the patients.

Percent of Patients With an Elevated White Blood Count at Baseline That Had Normalized at the End of Part I of the Study (Week 16)

White blood cells were measured in blood samples taken from the patients.

Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at the End of Part II of the Study (Week 40)

Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Physician Global Assessment of Disease Activity at the End of Part II of the Study (Week 40)

Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Patient/Parent Global Assessment of Overall Well-being at the End of Part II of the Study (Week 40)

Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Active Arthritis at the End of Part II of the Study (Week 40)

Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Limitation of Movement at the End of Part II of the Study (Week 40)

Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Erythrocyte Sedimentation Rate (ESR) at the End of Part II of the Study (Week 40)

Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward imputation for missing values.

Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) at the End of Part II of the Study (Week 40)

The Childhood Health Assessment Questionnaire-Disability Index (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. There are 4 possible responses to each question (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). A domain score is the highest score in that domain. To calculate the overall score, the patient must have a domain score in at least 6 of the 8 domains. The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A higher score indicates less ability. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward imputation for missing values.

Change From Baseline in the Pain Visual Analogue Scale (VAS) Score at the End of Part II of the Study (Week 40)

The patient or parent/guardian, as appropriate, provides a rating of the patient's pain (also called a discomfort index) on a 0 to 100 mm horizontal scale. The extreme left end of the line represents 'no pain' and the extreme right end represents 'very extreme pain'. A higher score indicates more pain. A negative change score indicates improvement. Change from baseline was calculated using last observation carried forward (LOCF) imputation for missing values. The analysis was adjusted for the randomization stratification factors background use of methotrexate and background use of oral corticosteroids, and the pain visual analog scale score at Baseline. The adjusted means from the fitted model are presented.

Percent of Patients With Inactive Disease at the End of Part II of the Study (Week 40)

Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at Weeks 2, 52, and 104

Percent of Patients With 4 Baseline Disease Characteristics Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at Week 104

A JIA ACR30/50/70/90 response is defined as a ≥ 30/50/70/90% response on 3 of 6 variables and no more than 1 of the remaining variables worsening > 30%. The 6 variables are physician global assessment of disease activity (20 units minimum on a 0-100 visual analog scale), parent/patient global assessment of overall well-being (20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0[best]-3[worst]). Results are reported for the subgroups: Previous biologic treatment (yes/no), concomitant methotrexate use (yes/no), rheumatoid factor (positive/negative), concomitant oral corticosteroid use (yes/no). Last observation carried forward was applied to missing components at visits.

Change From Baseline in the Juvenile Arthritis Disease Activity Score-71 (JADAS-71) at Week 104

The JADAS-71 is composed of 4 components: Physician global assessment of disease activity on a visual analog scale (VAS) (range = 0-10, left end of the line = arthritis inactive, ie, symptom-free and no arthritis symptoms; right end = arthritis very active), patient/parent global assessment of overall well-being on a VAS (range = 0-10, left end of the line = very well, ie, symptom-free and no arthritis disease activity; right end = very poor, ie, maximum arthritis disease activity), normalized erythrocyte sedimentation rate (ESR) (range = 0-10, If ESR is ≤ 20 mm/h, set to 0. If ≥ 120 mm/h, set to 10 mm/h. If > 20 mm/h and < 120 mm/h, apply formula: [ESR - 20 mm/h]/10 mm/h), and a count of active arthritis (swelling present or pain present and limitation of motion) in 71 selected joints (range=0-71). The JADAS-71 is the sum of the 4 component scores and ranges from 0-101. A higher score indicates more arthritis disease activity. A positive change score indicates improvement.

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Physician Global Assessment of Disease Activity at Week 104

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Patient/Parent Global Assessment of Overall Well-being at Week 104

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Active Arthritis at Week 104

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Limitation of Movement at Week 104

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Erythrocyte Sedimentation Rate (ESR) at Week 104

Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory. A negative change score indicates improvement.

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Functional Ability at Week 104

Percent of Patients With a Minimally Important Improvement in the Children's Health Assessment Questionnaire-Disability Index (CHAQ-DI) Score at Weeks 16, 40, 52, 80, and 104

The CHAQ-DI consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. There are 4 possible responses to each question (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). A domain score is the highest score in that domain. If aids and devices listed in the questionnaire or assistance from a person are required to perform a task, a domain score of 0 or 1 is increased to 2; if the domain score is 2 or 3, the domain score is not adjusted. To calculate the overall score, the patient must have a domain score in at least 6 of the 8 domains. The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A minimally important improvement is an improvement ≥ 0.13 over Baseline. Patients who withdrew due to non-safety reasons are classified as non-responders.

C-reactive Protein Levels From Baseline to Week 104

C-reactive protein (CRP), an acute phase protein, was measured in blood samples with a high-sensitivity CRP (hs-CRP) test using laser nephelometry.

Change From Baseline in the Pain Visual Analogue Scale (VAS) Score at Weeks 2, 40, 52, and 104

Percent of Patients With Inactive Disease From Week 16 to Week 104

Percent of Patients in Clinical Remission From Week 40 to 104

A patient was in clinical remission if they had inactive disease at all visits in the 6 months prior to and including the visit assessment day. A patient was judged to have inactive disease if all of the following criteria were met: Number of joints with active arthritis = 0; absence of active uveitis, defined by the adverse event preferred terms 'uveitis' and 'intermediate uveitis'; normal erythrocyte sedimentation rate (< 20 mm/hour regardless of age and sex); and physician's global assessment of overall well-being visual analog scale score ≤ 10. Patients who withdrew due to non-safety reasons are classified as non-responders.

Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at Week 104 by Duration of Disease (< 2 Years, ≥ 2 Years)

Oral Corticosteroid Dose at Baseline, Week 52, and Week 104

Due to the different types of corticosteroid medications available, the prednisone equivalent was used in the calculation of the oral corticosteroid dose. Values are based on the average daily dose on the study day and if not available the last observation carried forward is used.

Methotrexate Dose at Baseline, Week 52, and Week 104

Values are based on the average daily dose on the study day and if not available the last observation carried forward is used.

Height Standard Deviation Score at Baseline, Week 52, and Week 104

The height Standard Deviation Score was calculated using the following formula: (Observed height - median of the reference population)/standard deviation of the reference population. The reference population was defined as that of the same sex and age to the nearest completed year and month using the World Health Organization norms. A negative score indicates less height than the reference population.

Full Information

NCT ID

NCT00988221

First Posted

October 1, 2009

Last Updated

June 27, 2017

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT00988221

Brief Title

A Study of Tocilizumab in Patients With Active Polyarticular Juvenile Idiopathic Arthritis

Official Title

A 24 Week Randomized, Double-blind, Placebo-controlled Withdrawal Trial With a 16 Week Open-label lead-in Phase, and 64 Week Open-label Follow-up, to Evaluate the Effect on Clinical Response and the Safety of Tocilizumab in Patients With Active Polyarticular-course Juvenile Idiopathic Arthritis

Study Type

Interventional

2. Study Status

Record Verification Date

June 2017

Overall Recruitment Status

Completed

Study Start Date

November 30, 2009 (Actual)

Primary Completion Date

November 30, 2011 (Actual)

Study Completion Date

January 28, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

5. Study Description

Brief Summary

This 3-part study evaluated the efficacy and safety of tocilizumab in patients with active polyarticular-course juvenile idiopathic arthritis who have an inadequate response to, or were intolerant of methotrexate. In Part I of the study, all patients received intravenous (iv) infusions of tocilizumab (8 mg/kg for patients ≥ 30kg, 8 mg/kg or 10 mg/kg for patients < 30kg) every 4 weeks for 16 weeks. In Part II of the study, patients with an adequate response in Part I were randomized to receive either tocilizumab at the same dose as in Part I or placebo every 4 weeks for up to 24 weeks. In Part III of the study, patients received tocilizumab at the same dose as in Part I every 4 weeks for up to another 64 weeks. Standard of care therapy with or without non-steroidal anti-inflammatory drugs (NSAID), corticosteroids, or methotrexate was continued throughout the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Juvenile Idiopathic Arthritis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

188 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Tocilizumab 10 mg/kg in patients weighing < 30 kg

Arm Type

Experimental

Arm Description

Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.

Arm Title

Tocilizumab 8 mg/kg in patients weighing < 30 kg

Arm Type

Experimental

Arm Description

Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.

Arm Title

Tocilizumab 8 mg/kg in patients weighing ≥ 30 kg

Arm Type

Experimental

Arm Description

Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Patients received placebo to tocilizumab intravenously every 4 weeks.

Intervention Type

Drug

Intervention Name(s)

Tocilizumab

Other Intervention Name(s)

RoActemra, Actemra

Intervention Description

Tocilizumab was supplied as a sterile solution in vials.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo to tocilizumab was supplied as a sterile solution in vials.

Primary Outcome Measure Information:

Title

Percent of Patients With a Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30 (ACR30) Flare in Part II of the Study (Weeks 16-40)

Description

Time Frame

Week 16 through Week 40

Secondary Outcome Measure Information:

Title

Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses in Part I of the Study (Baseline to Week 16)

Description

Time Frame

Baseline to Week 16

Title

Description

Time Frame

Baseline to Week 16

Title

Description

Time Frame

Baseline to Week 16

Title

Description

Time Frame

Baseline to Week 16

Title

Description

Time Frame

Baseline to Week 16

Title

Description

Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory. A negative change score indicates improvement.

Time Frame

Baseline to Week 16

Title

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Functional Ability at the End of Part I of the Study (Week 16)

Description

Time Frame

Baseline to Week 16

Title

Juvenile Arthritis Disease Activity Score (JADAS-27) at the End of Part I of the Study (Week 16)

Description

Time Frame

Week 16

Title

Pain Visual Analogue Scale (VAS) Score at the End of Part I of the Study (Week 16)

Description

Time Frame

Week 16

Title

Percent of Patients With Inactive Disease at the End of Part I of the Study (Week 16)

Description

Time Frame

Week 16

Title

Percent of Patients With an Elevated C-reactive Protein Concentration at Baseline That Had Normalized at the End of Part I of the Study (Week 16)

Description

C-reactive protein (CRP), an acute phase protein, was measured in blood samples with a high-sensitivity CRP (hs-CRP) test using laser nephelometry.

Time Frame

Baseline to Week 16

Title

Percent of Patients With an Elevated Erythrocyte Sedimentation Rate at Baseline That Had Normalized at the End of Part I of the Study (Week 16)

Description

Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory.

Time Frame

Baseline to Week 16

Title

Percent of Patients With an Elevated Platelet Count at Baseline That Had Normalized at the End of Part I of the Study (Week 16)

Description

Platelets were measured in blood samples taken from the patients.

Time Frame

Baseline to Week 16

Title

Percent of Patients With an Elevated White Blood Count at Baseline That Had Normalized at the End of Part I of the Study (Week 16)

Description

White blood cells were measured in blood samples taken from the patients.

Time Frame

Baseline to Week 16

Title

Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at the End of Part II of the Study (Week 40)

Description

Time Frame

Week 40

Title

Description

Time Frame

Baseline to Week 40

Title

Description

Time Frame

Baseline to Week 40

Title

Description

Time Frame

Baseline to Week 40

Title

Description

Time Frame

Baseline to Week 40

Title

Description

Time Frame

Baseline to Week 40

Title

Description

Time Frame

Baseline to Week 40

Title

Change From Baseline in the Pain Visual Analogue Scale (VAS) Score at the End of Part II of the Study (Week 40)

Description

Time Frame

Baseline to Week 40

Title

Percent of Patients With Inactive Disease at the End of Part II of the Study (Week 40)

Description

Time Frame

Week 40

Title

Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at Weeks 2, 52, and 104

Description

Time Frame

Week 2 to Week 104

Title

Percent of Patients With 4 Baseline Disease Characteristics Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at Week 104

Description

A JIA ACR30/50/70/90 response is defined as a ≥ 30/50/70/90% response on 3 of 6 variables and no more than 1 of the remaining variables worsening > 30%. The 6 variables are physician global assessment of disease activity (20 units minimum on a 0-100 visual analog scale), parent/patient global assessment of overall well-being (20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0[best]-3[worst]). Results are reported for the subgroups: Previous biologic treatment (yes/no), concomitant methotrexate use (yes/no), rheumatoid factor (positive/negative), concomitant oral corticosteroid use (yes/no). Last observation carried forward was applied to missing components at visits.

Time Frame

Week 104

Title

Change From Baseline in the Juvenile Arthritis Disease Activity Score-71 (JADAS-71) at Week 104

Description

Time Frame

Baseline to Week 104

Title

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Physician Global Assessment of Disease Activity at Week 104

Description

Time Frame

Baseline to Week 104

Title

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Patient/Parent Global Assessment of Overall Well-being at Week 104

Description

Time Frame

Baseline to Week 104

Title

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Active Arthritis at Week 104

Description

Time Frame

Baseline to Week 104

Title

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Limitation of Movement at Week 104

Description

Time Frame

Baseline to Week 104

Title

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Erythrocyte Sedimentation Rate (ESR) at Week 104

Description

Erythrocyte sedimentation rate, an acute phase protein, was measured using a kit furnished by the study central laboratory. A negative change score indicates improvement.

Time Frame

Baseline to Week 104

Title

Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Functional Ability at Week 104

Description

Time Frame

Baseline to Week 104

Title

Percent of Patients With a Minimally Important Improvement in the Children's Health Assessment Questionnaire-Disability Index (CHAQ-DI) Score at Weeks 16, 40, 52, 80, and 104

Description

Time Frame

Baseline to Week 104

Title

C-reactive Protein Levels From Baseline to Week 104

Description

C-reactive protein (CRP), an acute phase protein, was measured in blood samples with a high-sensitivity CRP (hs-CRP) test using laser nephelometry.

Time Frame

Baseline to Week 104

Title

Change From Baseline in the Pain Visual Analogue Scale (VAS) Score at Weeks 2, 40, 52, and 104

Description

Time Frame

Baseline to Week 104

Title

Percent of Patients With Inactive Disease From Week 16 to Week 104

Description

Time Frame

Week 16 to Week 104

Title

Percent of Patients in Clinical Remission From Week 40 to 104

Description

Time Frame

Week 40 to Week 104

Title

Description

Time Frame

Baseline to Week 104

Title

Oral Corticosteroid Dose at Baseline, Week 52, and Week 104

Description

Time Frame

Baseline to Week 104

Title

Methotrexate Dose at Baseline, Week 52, and Week 104

Description

Values are based on the average daily dose on the study day and if not available the last observation carried forward is used.

Time Frame

Baseline to Week 104

Title

Height Standard Deviation Score at Baseline, Week 52, and Week 104

Description

Time Frame

Baseline to Week 104

10. Eligibility

Sex

All

Minimum Age & Unit of Time

2 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Children/juveniles, 2-17 years of age. Polyarticular-course juvenile idiopathic arthritis (pcJIA) ≥ 6 months duration. Active disease (≥ 5 active joints, ≥ 3 with limitation of motion). Inadequate response to or inability to tolerate methotrexate. Methotrexate, oral corticosteroids, and non-steroidal anti-inflammatory drugs (NSAID) at stable dose(at least 8, 4, and 2 weeks,respectively) prior to baseline. Biologics discontinued, between at least 1 and 20 weeks prior to baseline, depending on biologic. Exclusion Criteria: Auto-immune, rheumatic disease or overlap syndrome other than pcJIA. Wheelchair bound or bedridden. Intra-articular, intramuscular, intravenous, or long-acting corticosteroids within 4 weeks prior to baseline. Disease-modifying anti-rheumatic drugs (DMARD) (other than methotrexate) within 4 weeks prior to baseline. Previous treatment with tocilizumab.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

Facility Information:

Facility Name

Connecticut Children's Medical Center; 5E Clinical Trials Unit

City

Hartford

State/Province

Connecticut

ZIP/Postal Code

06106

Country

United States

Facility Name

Children's National Medical Center; Pediatric Rheumatology

City

Washington, D.C.

State/Province

District of Columbia

ZIP/Postal Code

20010-2970

Country

United States

Facility Name

Delray Research Associates

City

Delray Beach

State/Province

Florida

ZIP/Postal Code

33484

Country

United States

Facility Name

Miami Children's Hospital

City

Miami

State/Province

Florida

ZIP/Postal Code

33155-3009

Country

United States

Facility Name

The University of Chicago;Department of Pediatrics

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60649

Country

United States

Facility Name

University of Louisville Research Foundation, Inc; Kosair Charities Pediatric Clinical Research Unit

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40202

Country

United States

Facility Name

Children's Hospital

City

New Orleans

State/Province

Louisiana

ZIP/Postal Code

70118

Country

United States

Facility Name

Hackensack University Medical Center; Pediatric Rheumatology

City

Hackensack

State/Province

New Jersey

ZIP/Postal Code

07601

Country

United States

Facility Name

Cincinnati Children'S Hospital Medical Center; Division of Rheumatology

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45229-3039

Country

United States

Facility Name

Healthcare Research Consultants

City

Tulsa

State/Province

Oklahoma

ZIP/Postal Code

74135

Country

United States

Facility Name

Hospital Gral de Niños Pedro Elizalde

City

Buenos Aires

ZIP/Postal Code

1270

Country

Argentina

Facility Name

Hospital de Niños; Reumatologia

City

Buenos Aires

ZIP/Postal Code

1425

Country

Argentina

Facility Name

Caici; Rheumatology

City

Rosario

ZIP/Postal Code

S2000PBJ

Country

Argentina

Facility Name

Centro Medico Privado de Reumatologia; Reumathology

City

San Miguel

ZIP/Postal Code

T4000AXL

Country

Argentina

Facility Name

Westmead Hospital; Paediatric Rheumatology

City

Westmead

State/Province

New South Wales

ZIP/Postal Code

2145

Country

Australia

Facility Name

Royal Children'S Hospital; Paediatric Rheumatology

City

Parkville

State/Province

Victoria

ZIP/Postal Code

3052

Country

Australia

Facility Name

Princess Margaret Children'S Hospital; Department of Immunology

City

Subiaco

State/Province

Western Australia

ZIP/Postal Code

6008

Country

Australia

Facility Name

UZ Gent

City

Gent

ZIP/Postal Code

9000

Country

Belgium

Facility Name

UZ Leuven Gasthuisberg

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

Hospital Universitario Pedro Ernesto; Nucleo de Estudos da Saude do Adolescente

City

Rio de janeiro

State/Province

ZIP/Postal Code

20551030

Country

Brazil

Facility Name

Instituto de Puericultura E Pediatria Martagão Gesteira

City

Rio de Janeiro

State/Province

ZIP/Postal Code

21941-912

Country

Brazil

Facility Name

Hospital das Clinicas - UFRGS

City

Porto Alegre

State/Province

ZIP/Postal Code

90035-003

Country

Brazil

Facility Name

Hospital das Clinicas - FMUSP; Instituto da Crianca - Reumatologia

City

Sao Paulo

State/Province

ZIP/Postal Code

05403-000

Country

Brazil

Facility Name

Alberta Children'S Hospital

City

Calgary

State/Province

Alberta

ZIP/Postal Code

T3B 6A8

Country

Canada

Facility Name

British Columbia Children's Hospital; Rheumatology

City

Vancouver

State/Province

British Columbia

ZIP/Postal Code

V5Y 2C6

Country

Canada

Facility Name

Children'S Hospital of Eastern Ontario

City

Ottawa

State/Province

Ontario

ZIP/Postal Code

K1H 8L1

Country

Canada

Facility Name

Hospital For Sick Children

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 1X8

Country

Canada

Facility Name

Hôpital Pellegrin; Urgences Pédiatriques

City

Bordeaux

ZIP/Postal Code

33076

Country

France

Facility Name

CH de Bicêtre; Pediatrie Generale

City

Le Kremlin Bicêtre

ZIP/Postal Code

94275

Country

France

Facility Name

Hôpital Lapeyronie; Immuno-Rhumatologie Pr Jorgensen

City

Montpellier

ZIP/Postal Code

34295

Country

France

Facility Name

Hopital Cochin; Rhumatologie A

City

Paris

ZIP/Postal Code

75679

Country

France

Facility Name

Hop Necker Enfants Malades;UIH

City

Paris

ZIP/Postal Code

75743

Country

France

Facility Name

Hopitaux De Brabois; Medecine Infantile II

City

Vandoeuvre Les Nancy

ZIP/Postal Code

54511

Country

France

Facility Name

Charité Campus; Virchow Klinikum Berlin

City

Berlin

ZIP/Postal Code

13353

Country

Germany

Facility Name

Klinik Bremen-Mitte; Prof. Hess-Kinderklinik

City

Bremen

ZIP/Postal Code

28177

Country

Germany

Facility Name

Clementine Hospital; Kinder- und Jugendrheumatologie

City

Frankfurt/Main

ZIP/Postal Code

60316

Country

Germany

Facility Name

Asklepios Klinik; Zentrum fuer Allgemeine Paediatrie und Neonatologie

City

Sankt Augustin

ZIP/Postal Code

53757

Country

Germany

Facility Name

Irccs Ospedale Pediatrico Bambin Gesu - Dip. Di Medicina

City

Roma

State/Province

Lazio

ZIP/Postal Code

00165

Country

Italy

Facility Name

IRCCS G. Gaslini; Pediatria II

City

Genova

State/Province

Liguria

ZIP/Postal Code

16147

Country

Italy

Facility Name

ASST CENTRO SPECIALISTICO ORTOPEDICO TRAUMATO-LOGICO GAETANO PINI/CTO; Reumatol. Pediatrica

City

Milano

State/Province

Lombardia

ZIP/Postal Code

20122

Country

Italy

Facility Name

Nuovo Ospedale Pediatrico Meyer; Reumatologia - Clinica Pediatrica 1°

City

Firenze

State/Province

Toscana

ZIP/Postal Code

50139

Country

Italy

Facility Name

Univ. Di Padova - Dip. Di Pediatria - Unita' Reumatol. Pediatrica

City

Padova

State/Province

Veneto

ZIP/Postal Code

35128

Country

Italy

Facility Name

Cif Biotec Medica Sur

City

Mexico City, Distrito Federal

ZIP/Postal Code

14050

Country

Mexico

Facility Name

Inst. Mexicano de Investigacion Clinica

City

Mexico City

ZIP/Postal Code

06700

Country

Mexico

Facility Name

Cliditer SA de CV

City

Miexico City

ZIP/Postal Code

06700

Country

Mexico

Facility Name

Hospital Universitario Dr. Jose Eleuterio Gonzalez; Pediatria

City

Monterrey

ZIP/Postal Code

64460

Country

Mexico

Facility Name

Clinica San Felipe; Consultorio de Reumatología

City

Lima

ZIP/Postal Code

Country

Peru

Facility Name

Clinica San Borja; Servicio De Reumatologia

City

Lima

ZIP/Postal Code

Lima 41

Country

Peru

Facility Name

Instituto Nacional De Salud Del Niño

City

Lima

Country

Peru

Facility Name

Wojewodzki Szpital Dzieciecy Im. J. Brudzinskiego

City

Bydgoszcz

ZIP/Postal Code

85-667

Country

Poland

Facility Name

Wojewodzki Specjalistyczny Szpital Dzieciecy Sw Ludwika; Oddzial Dzieci Starszych

City

Kraków

ZIP/Postal Code

31-503

Country

Poland

Facility Name

Uniwersytecki Szpital Kliniczny Nr 4 im. M. Konopnickiej; Oddz. Kardiolog. i Reumatolog. dla Dzieci

City

Lodz

ZIP/Postal Code

91-738

Country

Poland

Facility Name

Dzieciecy Szpital Kliniczny IM. Prof. A. Gebali; Oddzial Pediatrii Chorob Pluc I Reumatologii

City

Lublin

ZIP/Postal Code

20-093

Country

Poland

Facility Name

Centrum Pediatrii im Jana Pawla II; Oddzial Reumatologiczny

City

Sosnowiec

ZIP/Postal Code

41-218

Country

Poland

Facility Name

Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im. Prof. Eleonory Reicher

City

Warszawa

ZIP/Postal Code

02-637

Country

Poland

Facility Name

FSBI "Scientific Research Institute of Rheumatology" of russian Academy of Medical Sciences

City

Moscow

ZIP/Postal Code

115522

Country

Russian Federation

Facility Name

SI Sceintific children health center RAMS

City

Moscow

ZIP/Postal Code

119991

Country

Russian Federation

Facility Name

I. M. Sechenov Moscow State Medical University; The Ministry of Health and Social Development of RF

City

Moscow

ZIP/Postal Code

119992

Country

Russian Federation

Facility Name

Southern District Medical Center of Roszdrav

City

Rostov-Na-Donu

ZIP/Postal Code

344019

Country

Russian Federation

Facility Name

Saint-Petersburg State; Pediatrics Medical Academy

City

Saint-Petersburg

ZIP/Postal Code

194100

Country

Russian Federation

Facility Name

Samara Regional Clinical Cardiology Dispensary

City

Samara

ZIP/Postal Code

443070

Country

Russian Federation

Facility Name

Hospital Universitario Reina Sofia; Servicio de Reumatologia

City

Cordoba

ZIP/Postal Code

14004

Country

Spain

Facility Name

Hospital General Universitario Gregorio Marañon; Servicio de Reumatología

City

Madrid

ZIP/Postal Code

28007

Country

Spain

Facility Name

Hospital Ramon y Cajal ; Servicio de Reumatologia

City

Madrid

ZIP/Postal Code

28034

Country

Spain

Facility Name

Hospital Universitario Virgen Macarena; Servicio de Reumatologia

City

Sevilla

ZIP/Postal Code

41009

Country

Spain

Facility Name

Hospital Universitario la Fe: Servicio de Reumatologia Pediatrica

City

Valencia

ZIP/Postal Code

46026

Country

Spain

Facility Name

Bristol Royal Hospital For Children

City

Bristol

ZIP/Postal Code

BS2 8BJ

Country

United Kingdom

Facility Name

Royal Liverpool Childrens Hospital; Rheumatology

City

Liverpool

ZIP/Postal Code

L12 2AP

Country

United Kingdom

Facility Name

Great Ormond Street Hospital for Sick Children; Institute of Child Health

City

London

ZIP/Postal Code

WC1N IEH

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

32912276

Citation

Malattia C, Ruperto N, Pederzoli S, Palmisani E, Pistorio A, Wouters C, Dolezalova P, Flato B, Garay S, Giancane G, Wells C, Douglass W, Brunner HI, De Benedetti F, Ravelli A; Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). Tocilizumab may slow radiographic progression in patients with systemic or polyarticular-course juvenile idiopathic arthritis: post hoc radiographic analysis from two randomized controlled trials. Arthritis Res Ther. 2020 Sep 10;22(1):211. doi: 10.1186/s13075-020-02303-y.

Results Reference

derived

PubMed Identifier

30824645

Citation

Pardeo M, Wang J, Ruperto N, Alexeeva E, Chasnyk V, Schneider R, Horneff G, Huppertz HI, Minden K, Onel K, Zemel L, Martin A, Kone-Paut I, Siamopoulou-Mavridou A, Silva CA, Porter-Brown B, Bharucha KN, Brunner HI, De Benedetti F; Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). Neutropenia During Tocilizumab Treatment Is Not Associated with Infection Risk in Systemic or Polyarticular-course Juvenile Idiopathic Arthritis. J Rheumatol. 2019 Sep;46(9):1117-1126. doi: 10.3899/jrheum.180795. Epub 2019 Mar 1.

Results Reference

derived

PubMed Identifier

24834925

Citation

Brunner HI, Ruperto N, Zuber Z, Keane C, Harari O, Kenwright A, Lu P, Cuttica R, Keltsev V, Xavier RM, Calvo I, Nikishina I, Rubio-Perez N, Alexeeva E, Chasnyk V, Horneff G, Opoka-Winiarska V, Quartier P, Silva CA, Silverman E, Spindler A, Baildam E, Gamir ML, Martin A, Rietschel C, Siri D, Smolewska E, Lovell D, Martini A, De Benedetti F; Paediatric Rheumatology International Trials Organisation PRINTO; Pediatric Rheumatology Collaborative Study Group (PRCSG). Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial. Ann Rheum Dis. 2015 Jun;74(6):1110-7. doi: 10.1136/annrheumdis-2014-205351. Epub 2014 May 16.

Results Reference

derived

Learn more about this trial

A Study of Tocilizumab in Patients With Active Polyarticular Juvenile Idiopathic Arthritis

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