AB0827 OFF-LABEL USE OF BIOLOGICS AND SMALL MOLECULES IN SJÖGREN DISEASE: REAL-WORLD DATA FROM THE INTERNATIONAL SJÖGREN BIG DATA COHORT
Authors: L. Quartuccio, P. Brito-Zeron, M. Rischmueller, A. Y. S. Lee, V. Fernandes Moça Trevisani, S. Pasoto, V. Valim, F. Reis de Oliveira, B. Hofauer, A. Szántó, C. Baldini, F. Carubbi, F. Atzeni, R. Priori, E. Bartoloni, R. Giacomelli, G. Hernandez-Molina, Y. Suzuki, C. Jurcut, E. Fonseca-Aizpuru, R. Solans-Laqué, M. Akasbi Montalvo, C. Fugmann, N. Inanc, B. Armagan, A. Rasmussen, A. Flores-Chávez, M. Ramos-Casals
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Sjögren disease (SjD) is a chronic autoimmune disorder characterized by inflammation of the exocrine glands, particularly the salivary and lacrimal glands, leading to dryness of the eyes and mouth. Current therapeutic options for SjD are empirical, due to the lack of evidence-based recommendations. However, off-label use of biologics or small molecules, particularly B-cell targeted therapies, is applied in some clinical scenarios in SjD. Research on the use of targeted therapies in SjD is ongoing, and several clinical trials are exploring their efficacy. <h3>Objectives:</h3> To analyse the off-label use of biologic and small molecule therapies in treating complicated/severe SjD using real-world data. <h3>Methods:</h3> The Big Data Project Consortium is an international, multicentre registry created in 2014. The inclusion criteria were the fulfilment of the 2002/2016 classification criteria. By December 2023, the participant centers had included 16703 valid patients from 28 countries. We have retrospectively analysed the use of biological and small molecule therapies in SjD, including the pharmacological classification of the used drugs, therapeutic indications, sequential and combination use, and causes of mortality. <h3>Results:</h3> The use of biologics and small molecules was reported in 330 (2%) patients, who received 359 therapeutic courses. We identified 23 different therapies that overwhelmingly consisted of B-cell targeted drugs (83%); more rarely, the drugs used targeted T cells (8%), tyrosine kinases (2.5%), TNF (2.5%), cytokines (2%), integrins (0.6%), and complement (0.3%). B-cell targeted therapies overwhelmingly consisted of rituximab (79%), followed by belimumab (4%), and isolated cases of use of obinutuzumab and ofatumumab (&lt;1%). T-cell targeted therapies included the use abatacept (8%); a large list of other biologics and small molecule inhibitors (16 different drugs) were used in less than 5 cases per drug. Combined biologic therapies were reported in only four patients (belimumab plus rituximab). The main therapeutic indication consisted of ESSDAI severe involvements that predominantly affected a single organ (57%), followed by the treatment of lymphoma (23%), and by severe systemic multiorgan involvement (18%). According to the predominantly affected ESSDAI domain, besides lymphadenopathy, the most frequent indications included articular (20%), pulmonary (7%), PNS (6%), CNS (6%), and cutaneous (5%) involvements (Figure 1). Death was reported in 32 patients (10%), with the most frequent causes being infection (34%) and cancer progression (31%). It should be noted that 4 (36%) of the 11 patients who died from infection were caused by COVID-19 (all of them were under treatment with rituximab). <h3>Conclusion:</h3> The real-life use of biologic and small molecule therapies in patients with SjD is exceptional (2%), a fact closely related to their off-label use in most therapeutic indications. Nearly 85% of therapies are directed against B cells (overwhelmingly rituximab), with exceptional cases of new anti-CD20 monoclonal antibodies or combined therapy with rituximab and belimumab. Mortality is higher than expected in SjD treated with the biologic and small molecule therapies [1], infections (notably COVID-19 in patients treated with rituximab) and cancer progression being the most frequent causes of death, thus highlighting the need for defining advanced treatment indications in SjD. <h3>REFERENCES:</h3> [1] Brito-Zeron P, et al. EClinicalMedicine. 2023; 61(4):102062. doi: 10.1016/j.eclinm.2023.102062 <h3>Acknowledgements:</h3> MD Juliana Viana Baiao Lemos, collaborator from Rheumatology Department, Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto Universidade de Sao Paulo, Brazil. <h3>Disclosure of Interests:</h3> <b>None declared.</b>