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

Primary Purpose

Rheumatoid Arthritis, Juvenile Idiopathic Arthritis

Status

Unknown status

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

Sampling of blood

About this trial

This is an interventional health services research trial for Rheumatoid Arthritis focused on measuring Rheumatoid arthritis, Juvenile Idiopathic Arthritis, Biopharmaceutical, Immunogenicity, Anti-Drug Antibody, Prediction

Eligibility Criteria

2 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

CHU Bicêtre

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Global population

Arm Description

All included patients : Sampling of blood

Outcomes

Primary Outcome Measures

Immunization against the Biopharmaceutical defined by the presence of ADAb within the first 12 months (or W52)

Secondary Outcome Measures

Quantification of ADAb

Clinical response and remission

European League Against Rheumatism (EULAR) response

Clinical response and remission

European League Against Rheumatism (EULAR) response

Clinical response and remission

European League Against Rheumatism (EULAR) response

Clinical response and remission

European League Against Rheumatism (EULAR) response

Clinical response and remission

European League Against Rheumatism (EULAR) response

Clinical response and remission

European League Against Rheumatism (EULAR) response

ADAb-associated adverse clinical events at any time point

Drug levels

Concentration in mg/L

Full Information

NCT ID

NCT02116504

First Posted

April 3, 2014

Last Updated

November 24, 2016

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Institut National de la Santé Et de la Recherche Médicale, France, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Leiden University Medical Center, University College London (UCL) Cancer Institute, University of Florence, Pediatric Rheumatology International Trials Organization, Istituto Giannina Gaslini, GlaxoSmithKline, University Hospital, Tours

1. Study Identification

Unique Protocol Identification Number

NCT02116504

Brief Title

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

Acronym

ABI-RA

Official Title

Multi-center Prospective European Cohort Study in Patients With Rheumatoid Arthritis or Juvenile Idiopathic Arthritis Planned to be Treated Independently of the Present Study, With the First Line of Adalimumab, Etanercept, Infliximab Therapy or With Rituximab or Tocilizumab (After Anti-Tumor Necrosis Factor Therapy or Another Biotherapy or in First Line)

Study Type

Interventional

2. Study Status

Record Verification Date

August 2016

Overall Recruitment Status

Unknown status

Study Start Date

April 2014 (undefined)

Primary Completion Date

April 2016 (Actual)

Study Completion Date

November 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

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

Rheumatoid Arthritis, Juvenile Idiopathic Arthritis

Keywords

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

7. Study Design

Primary Purpose

Health Services Research

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

156 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Global population

Arm Type

Other

Arm Description

All included patients : Sampling of blood

Intervention Type

Procedure

Intervention Name(s)

Sampling of blood

Intervention Description

Sampling of blood for dosage of antibodies

Primary Outcome Measure Information:

Title

Immunization against the Biopharmaceutical defined by the presence of ADAb within the first 12 months (or W52)

Time Frame

52 weeks

Secondary Outcome Measure Information:

Title

Quantification of ADAb

Time Frame

at Week 0

Title

Quantification of ADAb

Time Frame

at Week 4

Title

Quantification of ADAb

Time Frame

at Week 12

Title

Quantification of ADAb

Time Frame

at Week 26

Title

Quantification of ADAb

Time Frame

at Week 52

Title

Quantification of ADAb

Time Frame

at Week 64

Title

Quantification of ADAb

Time Frame

at Week 78

Title

Clinical response and remission

Description

European League Against Rheumatism (EULAR) response

Time Frame

at Week 4

Title

Clinical response and remission

Description

European League Against Rheumatism (EULAR) response

Time Frame

at Week 12

Title

Clinical response and remission

Description

European League Against Rheumatism (EULAR) response

Time Frame

at Week 26

Title

Clinical response and remission

Description

European League Against Rheumatism (EULAR) response

Time Frame

at Week 52

Title

Clinical response and remission

Description

European League Against Rheumatism (EULAR) response

Time Frame

at Week 64

Title

Clinical response and remission

Description

European League Against Rheumatism (EULAR) response

Time Frame

at Week 78

Title

ADAb-associated adverse clinical events at any time point

Time Frame

Until Week 78

Title

Drug levels

Description

Concentration in mg/L

Time Frame

Until week 78

10. Eligibility

Sex

All

Minimum Age & Unit of Time

2 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Xavier Mariette, MD, PhD

Organizational Affiliation

Assistance Publique - Hôpitaux de Paris

Official's Role

Principal Investigator

Facility Information:

Facility Name

CHU Bicêtre

City

Le Kremlin-Bicêtre

ZIP/Postal Code

94275

Country

France

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

35281074

Citation

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.

Results Reference

derived

PubMed Identifier

32192445

Citation

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.

Results Reference

derived

PubMed Identifier

29936438

Citation

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. Erratum In: Ann Rheum Dis. 2021 May;80(5):e84.

Results Reference

derived

Learn more about this trial

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

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