Balance Benefit / Risk of Immunomodulatory Treatments at the Child and Adolescent for Autoimmune Cytopenia. (VIGICAIRE)

National Study Backed by a Rare Disease Cohort the Benefit / Risk Balance of Immunomodulatory Treatments Prescribed in the Child and Adolescent for Autoimmune Cytopenia.

In France, a national prospective cohort for monitoring children and adolescents with autoimmune cytopenia OBS'CEREVANCE is in place since 2004. It is coordinated in Bordeaux by the Center's team. Reference Rare Diseases CEREVANCE. It has been validated by the French Data Protection Authority in 2009 (information note and written consent). It had mid 2013 more of 900 patients, and the data collected make it possible to study intentionally to treat the therapeutic management of patients with Chronic Immune-Thrombocytopenic Purpura, from Autoimmune Hemolytic Anemia, or from EVANS syndrome.

This study evaluates efficacy and tolerance at 6 months of treatment immunomodulators prescribed in France in real conditions of use, in children and adolescents under the age of 18, for a Chronic Immune-Thrombocytopenic Purpura, an Autoimmune Hemolytic Anemia or a simultaneous EVANS syndrome.

Study Overview

• Status: Completed
• Conditions: Immunotherapy; Immune Thrombocytopenic Purpura; Autoimmune Hemolytic Anemia; Evan Syndrome

Detailed Description

Chronic immunological thrombocytopenic purpura and anemia hemolytic autoimmune are rare autoimmune hematologic diseases, primary or secondary, affecting the child often very young, sometimes associated simultaneously or sequentially (Evans syndrome). They can be life-threatening, they in 20 to 50% of cases of prolonged dependence on immunosuppressants. The incidence of Immune-Thrombocytopenic Purpura is 2 to 5 / 100,000 inhabitants of under 18, the Autoimmune Hemolytic Anemia 5 to 10 times lower.

For the pediatric population, the experience reported in the literature is limited to individual cases or small series often retrospective and not comparative. It does not allow to have in 2013 a reasoning based on on evidence to define the second-line therapeutic strategy, in especially for Autoimmune Hemolytic Anemia where the therapeutic data are almost nonexistent. Splenectomy remains to this day the reference treatment of the Chronic Immune-Thrombocytopenic Purpura of the adult. In children, the therapeutic goal is to avoid it or to prevent it delay it. After failure of first-line treatments (immunoglobulins or corticosteroids) used for treatment of relapses or continuously, the main immunomodulatory treatments used in second line are azathioprine, ciclosporin, hydroxychloroquine, rituximab, mycophenolate mofetil, romiplostim, eltrombopag.

The benefit / risk balance of these 7 immunomodulatory treatments prescribed to the child for autoimmune cytopenia is presumed to be favorable based on the very limited data from the pediatric literature and the experience of most adults do not benefit from a specific marketing authorization.

• Study Type: Observational
• Enrollment (Actual): 454

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children or adolescents who have received one or more treatments of interest for a Chronic Immune-Thrombocytopenic Purpura, Autoimmune Hemolytic Anemia , or EVANS syndrome, in one of the 30 centers of the CEREVANCE network, will be identified and selected by the team CEREVANCE, in the OBS'CEREVANCE computer database created since 2004. The first second-line treatment they received will be analyzed.

Description

Inclusion Criteria:

• Patient initiating a first second-line immunomodulatory treatment (azathioprine, ciclosporine, eltrombopag, hydroxychloroquine, mycophénolate mofétil, rituximab, romiplostim), registered in the OBS'CEREVANCE database, presenting a Chronic Immune-Thrombocytopenic Purpura, Autoimmune Hemolytic Anemia or simultaneous EVANS syndrome.

Exclusion Criteria:

• Patient under immunosuppressant for another immunological pathology at the initiation of the first second line treatment,
• Patient treated with 2 second-line treatments on the same day,
• Oral refusal of participation of the patient or his legal representatives, after reading the information note specific for the study.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Haemorrhagic sign - Grade ≥ 3 (Buchanan score) Presence of a haemorrhagic sign ≥grade 3	Presence of a haemorrhagic sign ≥ grade 3 = moderate bleeding (Buchanan score : from 0 to 5)	At 6 months
Thrombocytopenia Presence of thrombocytopenia <30 G / L	Presence of thrombocytopenia <30 G / L	At 6 months
Need of a transfusion ?	Performing a transfusion : yes or no ?	At 6 months
Immunoglobulin IV Immunoglobulin IV	Immunoglobulin IV push	At 6 months
Corticoids push	Corticoid push (no reduction of their number during treatment follow-up versus non-treatment period)	At 6 months
Need a splenectomy ?	Performing a splenectomy : yes or no ?	At 6 months
Clinical signs of anemia	Presence of clinical signs of anemia ≥ grade 2 = Subject bedridden less than 50% of the day (WHO score : from 0 to 4)	At 6 months
Anemia	Presence of anemia <7g / dl Presence of anemia <7g / dl	At 6 months
Introduction of a new immunomodulatory treatment	Introduction of a new immunomodulatory treatment : yes or no ?	At 6 months
Stop treatment or not ?	Stop treatment because of failure, intolerance or non-compliance	At 6 months

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Investigators: Principal Investigator: Nathalie ALADJIDI, Dr, University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 18, 2016
• Primary Completion (ACTUAL): December 4, 2016
• Study Completion (ACTUAL): December 4, 2016

Study Registration Dates

• First Submitted: August 12, 2019
• First Submitted That Met QC Criteria: August 13, 2019
• First Posted (ACTUAL): August 15, 2019

Study Record Updates

• Last Update Posted (ACTUAL): August 15, 2019
• Last Update Submitted That Met QC Criteria: August 13, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Pediatrics; Cohort; CEREVANCE
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Anemia; Blood Coagulation Disorders; Skin Manifestations; Thrombocytopenia; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune
• Other Study ID Numbers: CHU BX 2013/24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Through this program, a coordinated and centralized analysis of reliable pharmacovigilance data will be transmitted in real time to the National Agency for Medicines. It will enable National Agency for Medicines to ensure the safe use of these treatments for the pediatric population, vulnerable, and optimize monitoring in the short and long term identified or potential risks of these treatments on a developing immune system. It will also ensure the monitoring of off-label or Temporary Therapeutic Protocol / Temporary recommendation for use prescriptions and to argue recommendations for good use. For treatments whose benefit will be confirmed, these results will be useful to the medical community to define the best second-line therapeutic strategy.