Anti-Biopharmaceutical Immunization: Prediction and Analysis of Clinical Relevance to Minimize the Risk of Immunization in Rheumatoid Arthritis Patients or Juvenile Idiopathic Arthritis Patients

NCT ID: NCT02116504

Last Updated: 2016-11-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 156 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2017-11-30

Brief Summary

One of the main potential causes of these failures of BP therapy response is the development of Anti-drug Anti-body (ADAb) in some patients. ADAb may decrease the efficacy of BPs by neutralizing them or modifying their clearance and they may be associated with BP-specific hypersensitivity reactions. The prediction, prevention and cure of anti-drug (AD) immunization are thus major goals in BP development. This prospective study (ABI-RA) will assess the occurrence of ADAb using standardized and validated assay(s) and also cellular, genetic and molecular parameters in RA/JIA patients treated with adalimumab, etanercept, infliximab and rituximab or tocilizumab, to address the mechanism of immunogenicity. Patient-related factors that might predispose an individual to an immune response will be taken into account: underlying disease, genetic background, immune status, including immunomodulating therapy and dosing schedule.

Detailed Description

The ABIRISK (Anti-biopharmaceutical Immunization: Prediction and analysis of clinical relevance to minimize the risk) consortium, within the IMI (Innovative Medicines Initiative), is a Public Private Partnership between pharmaceutical companies, academic institutions and clinical centers. The ABIRISK aims are to better analyze and predict the phenomenon of immunogenicity in order to reduce its occurrence. One of the main objectives of ABIRISK is to set up prospective cohort (ABI-RA) of patients with rheumatoid arthritis (RA) or juvenile idiopathic arthritis (JIA) to provide, using an integrated approach, new tools for being able to detect earlier and even before the beginning of the therapy, immunization to biopharmaceutical (BP). The introduction of BP has been a critical step forward in care for RA/JIA and 9 BP are now licensed for the treatment of RA/JIA. In spite of this progress, failure of response to BP is frequent and in most of the registries, less than 50 % of patients are still on drug at 5 years. These failures may be primary failures or secondary failures. The fact is that the low level of responses becomes insufficient compared to the expectations. One of the main potential causes of these failures of BP therapy response is the development of Anti-drug Anti-body (ADAb) in some patients. ADAb may decrease the efficacy of BPs by neutralizing them or modifying their clearance and they may be associated with BP-specific hypersensitivity reactions. The prediction, prevention and cure of anti-drug (AD) immunization are thus major goals in BP development. This prospective study (ABI-RA) will assess the occurrence of ADAb using standardized and validated assay(s) and also cellular, genetic and molecular parameters in RA/JIA patients treated with adalimumab, etanercept, infliximab and rituximab or tocilizumab, to address the mechanism of immunogenicity. Patient-related factors that might predispose an individual to an immune response will be taken into account: underlying disease, genetic background, immune status, including immunomodulating therapy and dosing schedule.

Conditions

Rheumatoid Arthritis; Juvenile Idiopathic Arthritis

Keywords

Rheumatoid arthritis; Juvenile Idiopathic Arthritis; Biopharmaceutical; Immunogenicity; Anti-Drug Antibody; Prediction

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: NONE

Study Groups

Global population

All included patients :

Sampling of blood

Group Type: OTHER

Sampling of blood

Intervention Type: PROCEDURE

Sampling of blood for dosage of antibodies

Interventions

Sampling of blood

Sampling of blood for dosage of antibodies

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Male and female patients of more than 18 years old diagnosed with RA according to 2010 ACR/EULAR criteria Or Male and female patients Age > 2 years and <18 years, diagnosed with JIA according to the Internal League Against Rheumatism (ILAR) classification criteria.
• Patient for whom the Treating Physician has decided to prescribe in the usual manner in accordance with the terms of the marketing authorization and independently from entry into this study:
• etanercept, adalimumab, infliximab, infliximab Biosimilar, rituximab OR tocilizumab in first line or after failure with other biotherapy. In case of previous rituximab, inclusion may be possible at least 6 months after the last rituximab infusion therapy or,
• Subcutaneous form of Tocilizumab, either as first line or after switch from infusion tocilizumab form is allowed.
• Having given written informed consent prior to undertaking any study-related procedures. For JIA patients, written informed consent signed by parents or legal representative and assent of the minor child
• Covered by a health insurance system where applicable, and/or in compliance with the recommendations of the national laws in force relating to biomedical research

Exclusion Criteria

• Under any administrative or legal supervision.
• Patients having previously anti-TNF if they are going to receive another anti-TNF therapy
• Patients having previously received rituximab in the past 6 months.
• Conditions/situations such as:

• Patients with conditions/concomitant diseases making them non evaluable for the primary endpoint
• Impossibility to meet specific protocol requirements (e.g. blood sampling)
• Patient is the Investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol
• Uncooperative or any condition that could make the patient potentially non-compliant to the study procedures
• Pregnant or breast-feeding women

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: collaborator

University College London (UCL) Cancer Institute

OTHER

Sponsor Role: collaborator

University of Florence

OTHER

Sponsor Role: collaborator

Pediatric Rheumatology International Trials Organization

OTHER

Sponsor Role: collaborator

Istituto Giannina Gaslini

OTHER

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

University Hospital, Tours

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xavier Mariette, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

CHU Bicêtre

Le Kremlin-Bicêtre, , France

Countries

France

References

Paoletti A, Ly B, Bitoun S, Nocturne G, Riviere E, Manson JJ, Matucci A, Pallardy M, De Vries N, Mariette X. Restoration of Default Blood Monocyte-Derived Macrophage Polarization With Adalimumab But Not Etanercept in Rheumatoid Arthritis. Front Immunol. 2022 Feb 23;13:832117. doi: 10.3389/fimmu.2022.832117. eCollection 2022.

Reference Type: DERIVED

PMID: 35281074 (View on PubMed)

Duhaze J, Caubet M, Hassler S, Bachelet D, Allez M, Deisenhammer F, Fogdell-Hahn A, Gleizes A, Hacein-Bey-Abina S, Mariette X, Pallardy M, Broet P; ABIRISK Consortium. Assessing the effect of genetic markers on drug immunogenicity from a mechanistic model-based approach. BMC Med Res Methodol. 2020 Mar 20;20(1):69. doi: 10.1186/s12874-020-00941-z.

Reference Type: DERIVED

PMID: 32192445 (View on PubMed)

Bitoun S, Nocturne G, Ly B, Krzysiek R, Roques P, Pruvost A, Paoletti A, Pascaud J, Donnes P, Florence K, Gleizes A, Hincelin-Mery A, Allez M, Hacein-Bey-Abina S, Mackay F, Pallardy M, Le Grand R, Mariette X. Methotrexate and BAFF interaction prevents immunization against TNF inhibitors. Ann Rheum Dis. 2018 Oct;77(10):1463-1470. doi: 10.1136/annrheumdis-2018-213403. Epub 2018 Jun 23.

Reference Type: DERIVED

PMID: 29936438 (View on PubMed)

Other Identifiers

2013-A01268-37

Identifier Type: OTHER

Identifier Source: secondary_id

ABI-RA-P01

Identifier Type: -

Identifier Source: org_study_id