AutoInflammatory Disease Alliance Registry (AIDA)

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

Overview

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, 11 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 * spondyloarthritis * Castleman disease

The registry will pursue the following aims within the first 36 months from the start of the enrollment:

1. to identify any association between clinical manifestations and gender, disease duration, body mass index and tabagism; 2. to detect differences in the clinical phenotype between pediatric-onset and adult-onset patients; 3. 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:

1. to overcome fragmentation in the clinical experience on these rare conditions by sharing the knowledge at the international level; 2. 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; 3. to identify the long-term clinical course of patients diagnosed with monogenic or polygenic AID; 4. to promote awareness among physicians and enhance early recognition of these diseases; 5. to describe the impact of AID on quality of life; 6. to identify any impact of monogenic and polygenic AID on fertility; 7. to study the course of AID during pregnancy; 8. to assess the socioeconomic impact of AID; 9. 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).

Interventions

• Other No intervention is foreseen by the protocol.
  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.

Primary outcome measures

• Change of the number of enrolled subjects [Time frame: 0-36-60-120 months]

Secondary outcome measures (12)

• Change in the disease activity score [Time frame: 0-36-60-120 months]
• Change in the % of patients with new organ involvement [Time frame: 0-36-60-120 months]
• Incidence of death or adverse events [Time frame: 0-36-60-120 months]
• Change in the inflammatory markers values (ESR) [Time frame: 0-36-60-120 months]
• Change in the inflammatory markers values (CRP and SAA) [Time frame: 0-36-60-120]
• Change in visual acuity expressed as Best Corrected Visual Acuity (BCVA) [Time frame: 0-36-60-120 months]
• Change in the overall function score [Time frame: 0-36-60-120 months]
• Change in the overall damage score [Time frame: 0-36-60-120 months]
• Change in articular pain measured as Visual Analogue Scale for articular Pain (VAS Pain) [Time frame: 0-36-60-120 months]
• Changes in height and weight percentile values for age and sex [Time frame: 0-36-60-120 months]
• Change in the % of patients experiencing fatigue [Time frame: 0-36-60-120 months]
• Change in the % of patients with fertility reduction or pregnancy complications [Time frame: 0-36-60-120]

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;
• to be diagnosed with spondyloarthritis according to ASAS and/or New York criteria;
• to be diagnosed with Castleman disease;

Exclusion criteria

\- informed consent/assent not provided by the patient and/or his/her legal representative.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Italy · 61 centers

• Azienda Ospedaliero-Universitaria Senese — Siena
• AOUC Policlinico di Bari — Bari
• University of Bari Medical School — Bari
• University-Hospital of Bari - UOC Medicina Interna — Bari
• University-Hospital of Bari - UOC Pediatria — Bari
• University-Hospital of Bari - UOC Reumatologia — Bari
• Central Hospital of Bolzano — Bolzano
• ASST degli Spedali Civili - P.O. Ospedale dei Bambini — Brescia
• … and 53 more centers

Turkey (Türkiye) · 11 centers

Center list to be confirmed — check the primary protocol.

Spain · 8 centers

Center list to be confirmed — check the primary protocol.

Egypt · 3 centers

• Mansoura University, Faculty of Medicine — Al Mansurah
• Al-Azhar University — Cairo
• Cairo University — Cairo

Greece · 3 centers

• Evangelismos General Hospital — Athens
• National and Kapodistrian University of Athens — Athens
• National and Kapodistrian University of Athens — Athens

Saudi Arabia · 3 centers

Center list to be confirmed — check the primary protocol.

Algeria · 2 centers

• University Algiers 1 — Algiers
• Université M'Hamed Bougara de Boumerdas — Boumerdas

Australia · 2 centers

• Flinders University — Adelaide
• University of Adelaide — Adelaide

China · 2 centers

• Peking University People's Hospital — Beijing
• The First Affiliated Hospital of Chongqing Medical University — Chongqing

India · 2 centers

• Prabha Eye Clinic & Research Centre — Bangalore
• Postgraduate Institute of Medical Education and Research — Chandigarh

Libya · 2 centers

Center list to be confirmed — check the primary protocol.

Mexico · 2 centers

Center list to be confirmed — check the primary protocol.

Poland · 2 centers

Center list to be confirmed — check the primary protocol.

Belgium · 1 center

• Antwerp University Hospital — Antwerp

Brazil · 1 center

• Hospital das Clinicas da Faculdade de Medicina HCFMUSP — São Paulo

Colombia · 1 center

• Universidad del Rosario - Escuela de Medicina Y Ciencias de La Salud — Bogotá

Germany · 1 center

• Universitätsklinikum Schleswig-Holstein — Lübeck

Iran · 1 center

• Shariati Hospital - Tehran University of Medical Sciences — Tehran

Martinique · 1 center

Center list to be confirmed — check the primary protocol.

Romania · 1 center

Center list to be confirmed — check the primary protocol.

Tunisia · 1 center

Center list to be confirmed — check the primary protocol.

Ukraine · 1 center

Center list to be confirmed — check the primary protocol.

Publications

• Gaggiano C, Vitale A, Obici L, Merlini G, Soriano A, Viapiana O, Cattalini M, Maggio MC, Lopalco G, Montin D, Jaber MA, Dagna L, Manna R, Insalaco A, Piga M, La Torre F, Berlengiero V, Gelardi V, Ciarcia L, Emmi G, Ruscitti P, Caso F, Cimaz R, Hernandez-Rodriguez J, Parronchi P, Sicignano LL, Verrecchia E, Iannone F, Sota J, Grosso S, Salvarani C, Frediani B, Giacomelli R, Mencarelli MA, Renieri A PMID 32831641
• Vitale A, Sota J, Obici L, Ricco N, Maggio MC, Cattalini M, Ruscitti P, Caso F, Manna R, Viapiana O, Caggiano V, Emmi G, Insalaco A, Montin D, Licciardi F, Soriano A, Dagna L, Salvarani C, Lamacchia V, Hernandez-Rodriguez J, Giacomelli R, Frediani B, Renieri A, Cantarini L. Role of Colchicine Treatment in Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS): Real-Life Data from the PMID 32565720
• Gaggiano C, Rigante D, Hernandez-Rodriguez J, Vitale A, Tarsia M, Soriano A, Lopalco G, Iannone F, Abdel Jaber M, Giacomelli R, Wiesik-Szewczyk E, Cattalini M, Frassi M, Piga M, Ragab G, Sota J, Zunica F, Floris A, Sabato V, Hegazy MT, Araujo O, Pelegrin L, Fabbiani A, Renieri A, Grosso S, Fabiani C, Frediani B, Cantarini L. Anakinra and canakinumab for patients with R92Q-associated autoinflammato PMID 34527082
• Sota J, Rigante D, Cimaz R, Cattalini M, Frassi M, Manna R, Sicignano LL, Verrecchia E, Aragona E, Maggio MC, Lopalco G, Emmi G, Parronchi P, Cauli A, Wiesik-Szewczyk E, Hernandez-Rodriguez J, Gaggiano C, Tarsia M, Mourabi M, Ragab G, Vitale A, Fabiani C, Frediani B, Lamacchia V, Renieri A, Cantarini L; Autoinflammatory Diseases Alliance (AIDA) and the Autoinflammatory Diseases Working Group of th PMID 33961014
• Sota J, Rigante D, Lopalco G, Emmi G, Gentileschi S, Gaggiano C, Ciarcia L, Berlengiero V, Mourabi M, Ricco N, Barneschi S, Mattioli I, Tosi GM, Frediani B, Tarsia M, di Scala G, Vitale A, Iannone F, Fabiani C, Cantarini L. Clinical profile and evolution of patients with juvenile-onset Behcet's syndrome over a 25-year period: insights from the AIDA network. Intern Emerg Med. 2021 Nov;16(8):2163-21 PMID 33835406
• Vitale A, Obici L, Cattalini M, Lopalco G, Merlini G, Ricco N, Soriano A, La Torre F, Verrecchia E, Insalaco A, Dagna L, Jaber MA, Montin D, Emmi G, Ciarcia L, Barneschi S, Parronchi P, Ruscitti P, Maggio MC, Viapiana O, Sota J, Gaggiano C, Giacomelli R, Sicignano LL, Manna R, Renieri A, Lo Rizzo C, Frediani B, Rigante D, Cantarini L. Biotechnological Agents for Patients With Tumor Necrosis Factor PMID 34307404
• Vitale A, Caggiano V, Sbalchiero J, Tufan A, Batu ED, Ragab G, Portincasa P, Conti G, Aragona E, Sota J, Gavioli F, Gaggiano C, De Paulis A, Sahin A, Maggio MC, Rigante D, Olivieri AN, Yildirim D, Kucuk H, Kardas RC, Vasi I, Ozen S, Bilginer Y, Sener S, Emreol HE, Mahmoud AAA, Ghanema M, Maher A, Saad MA, Jaber N, Khalil M, Di Ciaula A, De Palma L, Cuzzola R, Affronti A, Gambino F, Della Casa F, M PMID 40175882
• Tarsia M, Vitale A, Gaggiano C, Sota J, Maselli A, Bellantonio C, Guerriero S, Dammacco R, La Torre F, Ragab G, Hegazy MT, Fonollosa A, Paroli MP, Del Giudice E, Maggio MC, Cattalini M, Fotis L, Conti G, Mauro A, Civino A, Diomeda F, de-la-Torre A, Cifuentes-Gonzalez C, Tharwat S, Hernandez-Rodriguez J, Gomez-Caverzaschi V, Pelegrin L, Babu K, Gupta V, Minoia F, Ruscitti P, Costi S, Breda L, La Be PMID 38206518

Identifiers

NCT: NCT05200715 · AIDA V.04 19.05.2021

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗