AutoInflammatory Disease Alliance Registry (AIDA)

Study Overview
=================
Brief Summary
-----------------
Autoinflammatory diseases (AID) are clinical entities characterized by recurrent inflammatory attacks in absence of infection, neoplasm or deregulation of the adaptive immune system. Among them, hereditary periodic syndromes, also known as monogenic AID, represent the prototype of this disease group, caused by mutations in genes involved in the regulation of innate immunity, inflammation and cell death. Based on recent experimental acquisitions in the field of monogenic AID, several immunologic disorders have been reclassified as polygenic/multifactorial AID, sharing pathogenetic and clinical features with hereditary periodic fevers. This has paved the way to new treatment targets for patients suffering from rare diseases of unknown origin, including Behçet's disease, Still disease, Schnitzler's disease, PFAPA (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis) syndrome, chronic recurrent multifocal osteomyelitis (CRMO), non-infectious uveitis and scleritis. Gathering information on such rare conditions is made difficult by the small number of patients, along with the difficulty of obtaining an accurate diagnosis in non-specialized clinical settings. In this context, the AIDA project promotes international collaboration among clinical centres to develop a permanent registry aimed at collecting demographic, genetic, clinical and therapeutic data of patients affected by monogenic and polygenic AID, in order to expand the current knowledge of these rare conditions.

Detailed Description
-----------------
The AIDA registry service is based on REDCap (Research Electronic Data Capture, project-redcap.org), a secure web application for building and managing online surveys and databases, designed to support data capture for research studies. The platform is directly accessible through the AIDA website, after inserting a personal username and password. Currently, 9 registries are available, each one dedicated to the collection of data about: monogenic AID PFAPA syndrome undifferentiated systemic AID (USAID) Behçet's disease Schnitzler's disease VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome Still disease noninfectious uveitis noninfectious scleritis The registry will pursue the following aims within the first 36 months from the start of the enrollment: to identify any association between clinical manifestations and gender, disease duration, body mass index and tabagism; to detect differences in the clinical phenotype between pediatric-onset and adult-onset patients; to identify the impact of different treatment approaches on clinical and laboratory disease manifestations. Additional aims of the AIDA project, to be reached over the next 10 years, are the following: to overcome fragmentation in the clinical experience on these rare conditions by sharing the knowledge at the international level; to improve knowledge about the clinical presentation, genotype-phenotype correlations, response to treatment, long-term complications and social impact when monogenic and polygenic AID manifest during either childhood or adulthood; to identify the long-term clinical course of patients diagnosed with monogenic or polygenic AID; to promote awareness among physicians and enhance early recognition of these diseases; to describe the impact of AID on quality of life; to identify any impact of monogenic and polygenic AID on fertility; to study the course of AID during pregnancy; to assess the socioeconomic impact of AID; to promote future multicentric studies. Data collection is both retrospective and prospective. It includes demographic, clinical, diagnostic, genetic, clinimetric, laboratory, radiologic, therapeutic and socio-economic data. Instruments are designed to be filled out during routine clinical visits, usually scheduled every 3-6 months. Separation of personally identifiable information and medical data by using only pseudonyms for storing medical data ensures compliance with data protection regulations. The description of symptoms, diseases, procedures and injuries is based on the International Statistical Classification of Diseases and Related Health Problems (ICD)-10 coding system. Data management is both central and decentral. Data are extracted and statistically analyzed on a regular basis according to individual study protocols. A policy for authorship and dissemination of research findings is in place among the AIDA partners contributing to the registry. The AIDA registry will support data collection for the conduction of clinical trials, observational studies, comparative effectiveness research, and other research on patients with monogenic and polygenic AID. Several healthcare providers contributing to the AIDA Network are members of the European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA).

Official Title
-----------------
Development of an International Multicenter Registry of Patients With Monogenic and Polygenic Autoinflammatory Diseases Aimed at Clinical and Therapeutical Data Collection and Analysis

Conditions
-----------------
Hereditary Autoinflammatory Diseases, Schnitzler Syndrome, Behcet Syndrome, PFAPA Syndrome, Still Disease, Autoinflammatory Syndrome, Unspecified, Uveitis, Scleritis, Vexas Syndrome

Intervention / Treatment
-----------------
* Other: No intervention is foreseen by the protocol.


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: to be diagnosed with a monogenic AID according to the clinical phenotype and the detection of a confirmative genotype; to be diagnosed with clinical familial Mediterranean fever or Behçet's disease or Still disease or PFAPA syndrome or Schnitzler's disease or CRMO according to the corresponding clinical diagnostic and/or classification criteria; to be diagnosed with undifferentiated systemic AID; to be diagnosed with non-infectious uveitis according to the standardization for uveitis nomenclature (SUN) criteria; to be diagnosed with anterior or posterior non-infectious scleritis. Exclusion Criteria: - informed consent/assent not provided by the patient and/or his/her legal representative.
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients affected by autoinflammatory diseases<br> | Other: No intervention is foreseen by the protocol.<br>* Patients will be observed for 10 years at least. Demographic, genetic, clinical, clinimetric, laboratory, radiologic and therapeutic data will be collected both retrospectively and prospectively during routine follow-up visits.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the number of enrolled subjects | This is an observational registry. The primary outcome is the increase of the number of subjects enrolled within each nosologic group. | 0-36-60-120 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the disease activity score | Change in the disease activity score specific for the nosologic entity (BDCAF score, Pouchot score, modified Pouchot score, JADAS27/JADAS27(CRP), DAS28) or according to composite indexes that will be defined in each study based on the registry. | 0-36-60-120 months | 
| Change in the % of patients with new organ involvement |  | 0-36-60-120 months | 
| Incidence of death or adverse events |  | 0-36-60-120 months | 
| Change in the inflammatory markers values (ESR) | ESR measured in mm/h | 0-36-60-120 months | 
| Change in the inflammatory markers values (CRP and SAA) | CRP and SAA measured in mg/dl | 0-36-60-120 | 
| Change in visual acuity expressed as Best Corrected Visual Acuity (BCVA) |  | 0-36-60-120 months | 
| Change in the overall function score | Change in the overall function score according to HAQ (adults) or CHAQ (children) | 0-36-60-120 months | 
| Change in the overall damage score | Change in the overall damage score specific for the nosologic entity (ADDI score, BODI score, JADI score) | 0-36-60-120 months | 
| Change in articular pain measured as Visual Analogue Scale for articular Pain (VAS Pain) |  | 0-36-60-120 months | 
| Changes in height and weight percentile values for age and sex |  | 0-36-60-120 months | 
| Change in the % of patients experiencing fatigue |  | 0-36-60-120 months | 
| Change in the % of patients with fertility reduction or pregnancy complications |  | 0-36-60-120 | 
| Change in the socioeconomic indicators | Number of days lost at work/school during the last 3 months, Number of visits/ phone calls to the general practitioner during the last 3 months, Number of accesses to the Emergency Room during the last 6 months, Days of hospitalization during the last 3 months, Overall number of days lost at work by relatives during the last 3 months | 0-36-60-120 months |