In silico validation of the autoinflammatory disease damage index

Nienke M. Ter Haar, Amber Laetitia Justine Van Delft, Kim Valerie Annink, Henk Van Stel, Sulaiman M. Al-Mayouf, Gayane Amaryan, Jordi Anton, Karyl S. Barron, Susanne Benseler, Paul A. Brogan, Luca Cantarini, Marco Cattalini, Alexis Virgil Cochino, Fabrizio De Benedetti, Fatma Dedeoglu, Adriana Almeida De Jesus, Erkan Demirkaya, Pavla Dolezalova, Karen L. Durrant, Giovanna FabioRomina Gallizzi, Raphaela Goldbach-Mansky, Eric Hachulla, Veronique Hentgen, Troels Herlin, Michaël Hofer, Hal M. Hoffman, Antonella Insalaco, Annette F. Jansson, Tilmann Kallinich, Isabelle Kone-Paut, Anna Kozlova, Jasmin Beate Kuemmerle-Deschner, Helen J. Lachmann, Ronald M. Laxer, Alberto Martini, Susan Nielsen, Irina Nikishina, Amanda K. Ombrello, Seza Özen, Efimia Papadopoulou-Alataki, Pierre Quartier, Donato Rigante, Ricardo Russo, Anna Simon, Maria Trachana, Yosef Uziel, Angelo Ravelli, Grant Schulert, Marco Gattorno, Joost Frenkel*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Introduction Autoinflammatory diseases can cause irreversible tissue damage due to systemic inflammation. Recently, the Autoinflammatory Disease Damage Index (ADDI) was developed. The ADDI is the first instrument to quantify damage in familial Mediterranean fever, cryopyrin-associated periodic syndromes, mevalonate kinase deficiency and tumour necrosis factor receptor-associated periodic syndrome. The aim of this study was to validate this tool for its intended use in a clinical/research setting. Methods The ADDI was scored on paper clinical cases by at least three physicians per case, independently of each other. Face and content validity were assessed by requesting comments on the ADDI. Reliability was tested by calculating the intraclass correlation coefficient (ICC) using an â observer-nested-within-subject' design. Construct validity was determined by correlating the ADDI score to the Physician Global Assessment (PGA) of damage and disease activity. Redundancy of individual items was determined with Cronbach's alpha. Results The ADDI was validated on a total of 110 paper clinical cases by 37 experts in autoinflammatory diseases. This yielded an ICC of 0.84 (95% CI 0.78 to 0.89). The ADDI score correlated strongly with PGA-damage (r=0.92, 95% CI 0.88 to 0.95) and was not strongly influenced by disease activity (r=0.395, 95% CI 0.21 to 0.55). After comments from disease experts, some item definitions were refined. The interitem correlation in all different categories was lower than 0.7, indicating that there was no redundancy between individual damage items. Conclusion The ADDI is a reliable and valid instrument to quantify damage in individual patients and can be used to compare disease outcomes in clinical studies.

Original languageEnglish
Pages (from-to)1599-1605
Number of pages7
JournalAnnals of the Rheumatic Diseases
Issue number11
Publication statusPublished - 1 Nov 2018


  • familial Mediterranean fever
  • fever syndromes
  • inflammation


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