Pharmacovigilance in Juvenile Idiopathic Arthritis Patients Treated With Biologic Agents and/or Methotrexate (PharmaChild)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified May 2011 by Istituto Giannina Gaslini
Sponsor:
Collaborator:
Members of the PRINTO network (PRINTO at www.printo.it)
Information provided by:
Istituto Giannina Gaslini
ClinicalTrials.gov Identifier:
NCT01399281
First received: July 19, 2011
Last updated: July 20, 2011
Last verified: May 2011
  Purpose

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common chronic paediatric rheumatic disease (PRD) and an important cause of short and long-term disability. Although none of the available drugs for JIA has a curative potential, prognosis has greatly improved as a result of substantial progress in disease management. The therapeutic treatment of children with JIA encompasses the use of NSAIDs and intra-articular steroid injections. In those patients not responding to NSAIDs, methotrexate (MTX) has become the disease modifying anti-rheumatic drug (DMARD) of first choice worldwide. For children not responding to MTX, biologic agents recently have become treatment options.

PATIENTS AND METHODS: 3-10 year observation study related to children with JIA undergoing treatment with MTX or biologic agents with the following objectives:

  1. To create a long-term observational registry of a large population of prevalent and incident cases.
  2. Use the accumulating data in the registry to conduct (i) a pharmacovigilance/safety study (primary endpoint) and (ii) estimate effectiveness (frequency and magnitude of response, disease activity over time inhibition or slowing of joint erosions and other radiological evidence of disease progression,), and (iii) estimate adherence to the various treatment regimens. Data from the registry will be used to compare safety and effectiveness profiles amongst the patient cohorts.
  3. To identify clinical and laboratory predictors of safety, response to therapy, including remission This project has retrospective (first 3 years) and prospective components (up to 10 years) and will be conducted by the participating centres of the more than 50 countries belonging to the Paediatric Rheumatology INternational Trials Organisation (PRINTO certified ISO 9001-2008, www.printo.it), or the Pediatric Rheumatology European Society (PRES at www.pres.org.uk). The main role of these organisations is to provide a scientific basis for current treatments of paediatric rheumatic diseases.

The overall hypothesis to be tested is:

• Biologic agents ± MTX agents are able to maintain an acceptable safety profile in the long term in children with different JIA categories while achieving clinical remission and prevent/stop joint erosion development over time.

The overall aims are to establish the long term safety of biologic agents and MTX, and their relative effectiveness in children with JIA who need treatment with second line agents.


Condition
Juvenile Idiopathic Arthritis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Pharmacovigilance in Juvenile Idiopathic Arthritis Patients (Pharmachild) Treated With Biologic Agents and/or Methotrexate. A PRINTO/PRES Registry

Resource links provided by NLM:


Further study details as provided by Istituto Giannina Gaslini:

Primary Outcome Measures:
  • Safety in patients with JIA on biologics/MTX from 3 to 10 years from drug initiation [ Time Frame: 3-10 years ] [ Designated as safety issue: Yes ]
    To compare the long term incidence rates of emergent moderate, severe adverse events (AEs) and serious A (SAE) observed in paediatric subjects with JIA. This will include but not be limited to, malignancies, opportunistic infections, autoimmune events, cardiovascular events, central nervous system involvement (e.g. optic neuritis, demyelinating disease), infertility, gastrointestinal bleeding, macrophage activation syndrome (MAS).

  • Long-term efficacy in patients with JIA on biologics/MTX from 3 to 10 years from drug initiation [ Time Frame: 3-10 years ] [ Designated as safety issue: No ]
    To assess the long-term efficacy (magnitude of response, prevention or slowing of joint erosion and damage, and treatment adherence) of biologic agents and MTX for the treatment of children and adolescents with different categories of JIA.


Secondary Outcome Measures:
  • Predictors of safety from 3 to 10 years from drug initiation [ Time Frame: 3-10 years ] [ Designated as safety issue: Yes ]
    Identify predictors of safety (clinical or experimental, magnitude of response, remission)

  • Risk factor from 3 to 10 years from drug initiation [ Time Frame: 3-10 years ] [ Designated as safety issue: Yes ]
    Assess potential risk factors (e.g. concomitant medications or diseases, medical history etc), which may modify the safety profile of biologic agents and MTX;

  • Number of children in treatment with biologics from 3 to 10 years from drug initiation [ Time Frame: 3-10 years ] [ Designated as safety issue: No ]
    To assess the number of children in which a biologic agent is added to the treatment

  • Wrist joint erosion from 3 to 10 years from drug initiation [ Time Frame: 3-10 years ] [ Designated as safety issue: No ]
    Evaluate the progression of wrist joint erosion over time and abnormal growth/maturation in JIA subjects presenting a wrist involvement

  • Assess the reasons for stopping drug treatment from 3 to 10 years from drug initiation [ Time Frame: 3-10 years ] [ Designated as safety issue: Yes ]
    • To assess the reasons for stopping drug treatment

  • Efficacy from 3 to 10 years from drug initiation [ Time Frame: 3-10 years ] [ Designated as safety issue: No ]
    • To evaluate efficacy in terms, in the different JIA categories, of individual JIA core set variables, and the ACR Paediatric 30, 50, 70, 90, 100 criteria for improvement, and the achievement of clinical remission on and off medication as well as the occurrence of disease flare during biologic agents and MTX treatment course and after drug discontinuation, and the attainment of a status of minimal disease actvity (MDA)


Estimated Enrollment: 3000
Study Start Date: July 2011
Estimated Study Completion Date: March 2021
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Biologics alone or methotrexate alone
This group mainly refer to children with polyarticular course JIA treated with methotrexate ± biologics,
Biologics and MTX
JIA treated with a combination of biologic and MTX (including any other add on therapy e.g. cyclosporine, leflunomide etc). This group mainly refer to children with polyarticular course JIA treated with MTX ± biologics
NSAIDs and/or steroid injections alone
This group refers to children with mostly oligoarticular persistent course who are usually NOT treated with second line agents and have a more benign course.

Detailed Description:

Study Design This is a 3-10 year, international, multicentre, observational, safety and efficacy (response, joint erosion, damage, and treatment adherence) study aimed at collecting prospective safety, tolerability, efficacy, and treatment adherence information on JIA subjects exposed to any biologic agents and MTX, according to local standard of practice.

This is a non-interventional study, where the medicinal products are prescribed as per the investigator's decision. The assignment of the subject to a particular therapeutic strategy is not decided in advance by the study protocol, but falls within current practice and the prescription of the medicine is clearly separated from the decision to include the subject in the study. No additional diagnostic or monitoring procedures shall be applied to the subjects and epidemiological methods will be used for the analysis of collected data.

Duration and treatment will be as per investigator's decision. The nature and frequency of subjects' visits to the investigator's site will be determined only by the investigator, according to his/her judgment on the basis of the clinical evolution of the subject.

The duration of the study is expected to be at least 3 years from initiation of the first site and may be continued beyond if adequate funding is be available.

  Eligibility

Ages Eligible for Study:   1 Year to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Male and female patients with age <= 18 years at the time of enrollment, selected among the PRINTO centers as part of the routine standard of care

Criteria

Inclusion Criteria:

  • Signed written informed consent by subjects and /or parent or legally acceptable representative
  • JIA (any ILAR category) with age ≤ 18 years at the time of enrolment.
  • Subjects receiving biologic agents ± MTX, MTX alone, or NSAIDs and/or steroid injections only as per physician discretion.

Exclusion Criteria:

  • Contraindications to biologic agents and/or MTX treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01399281

Contacts
Contact: Nicolino Ruperto, MD, MPH +39-010-382854 nicolaruperto@ospedale-gaslini.ge.it

Locations
Italy
IRCCS G. Gaslini Not yet recruiting
Genoa, Italy, 16147
Principal Investigator: Nicolino Ruperto, MD, MPH         
Sponsors and Collaborators
Istituto Giannina Gaslini
Members of the PRINTO network (PRINTO at www.printo.it)
Investigators
Principal Investigator: Nicolino Ruperto, MD, MPH Istituto G. Gaslini/PRINTO
Study Director: PRINTO Member All PRINTO members which will receive ethics committee approval
  More Information

Additional Information:
Publications:

Responsible Party: Nicolino Ruperto, MD, MPH, PRINTO
ClinicalTrials.gov Identifier: NCT01399281     History of Changes
Other Study ID Numbers: EU 260353
Study First Received: July 19, 2011
Last Updated: July 20, 2011
Health Authority: European Union: European Medicines Agency

Keywords provided by Istituto Giannina Gaslini:
juvenile idiopathic arthritis, biologics, methotrexate

Additional relevant MeSH terms:
Arthritis
Arthritis, Juvenile
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014