IL-1 targeting agents in Schnitzler syndrome: a multicentre, real-world study from the international AIDA Network Schnitzler Registry
Year: 2025
Type: article
Study design: Observational Study
Abstract: OBJECTIVES: Schnitzler syndrome (SchS) is a rare autoinflammatory disease characterised by a primary pathogenic involvement of interleukin (IL)-1. Therefore, IL-1 blockers are currently considered the optimal therapeutic option for SchS patients. However, while IL-1 blockers are first-line for SchS, long-term real-world evidence is limited by the rarity of the disease. We assessed the long-term effectiveness and safety of the IL-1 inhibitors anakinra and canakinumab used in SchS, also looking for variables capable of affecting global effectiveness and drug retention over time. METHODS: Data analysed in this study were drawn from the international AutoInflammatory Disease Alliance (AIDA) Registry dedicated to SchS. RESULTS: 28 SchS patients corresponding to 37 treatment lines were included in the study. Complete and partial responses occurred in 73.1% and 29.9% of anakinra-treated patients, and 66.8% and 33.3% with canakinumab. The overall anakinra and canakinumab drug retention rates at 12-, 36-, and 60-month follow-up were 85.6%, 81.7% and 64.7%, respectively; the probability of discontinuing IL-1 inhibitors at 12-, 36- and 60 months due to loss of effectiveness was 9.6%, 13.7% and 24.5%, respectively. The maximum IgG M-protein levels were found to be significantly higher in patients achieving partial response compared to those benefiting from complete response (p=0.032). Lymphadenopathy independently predicted anti-IL-1 discontinuation due to loss of effectiveness (HR 7.78, 95% CI: 1.27-47.9; p=0.027). CONCLUSIONS: The present study confirms the high effectiveness of IL-1 inhibitors in controlling SchS, including the complete and partial response rates and the long-term survival. Elevated IgG M-protein levels and the presence of lymphadenopathy should be considered as potential indicators for identifying patients more likely to exhibit a partial response and a possible loss of treatment efficacy.
Authors: Laura Calabrese, Alessandra Cartocci, Antonio Vitale, Eduardo Martín-Nares, Martina D’Onghia, Valeria Caggiano, Jiram Torres-Ruiz, Roberta Lopez, Karina Jahnz-Rozyk, Katarzyna Rybak, Micol Frassi, Franco Franceschini, Francesca Crisafulli, Abdurrahman Tufan, Hamit Kucuk, Aslihan Avanoglu Guler, Antonio Gidaro, Leyla La Cava, Francesca Della Casa, Ilaria Mormile, Elisa Cinotti, Giuseppe Lopalco, Jurgen Sota, Jessica Sbalchiero, Giacomo Emmi, Andreas Recke, Stefania Costi, Paolo Sfriso, Sara Monti, Ombretta Viapiana, Andrea Hinojosa-Azaola, Alberto Balistreri, Claudia Fabiani, Bruno Frediani, Pietro Rubegni, Ewa Wiesik-Szewczyk, Luca Cantarini
Institutions: University of Siena, Università Cattolica del Sacro Cuore, Azienda Ospedaliera Universitaria Senese, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Central Clinical Hospital, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, University of Brescia, Gazi University, University of Milan, Luigi Sacco Hospital, University of Naples Federico II, University of Bari Aldo Moro, University of Trieste, Monash Medical Centre, Ospedale di Cattinara, Monash University, University Hospital Schleswig-Holstein, University of Padua, University of Pavia, Policlinico San Matteo Fondazione, University of Verona, Azienda Ospedaliera Universitaria Integrata Verona
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Funder: Università degli Studi di Siena
OpenAlex ID: W4415479366