PO:14:197 | Safety of biologic and conventional immunosuppressants in an Italian cohort of patients with systemic lupus erythematosus: a longitudinal analysis from the Lupus Italian Registry pharmacoepidemiologic study promoted by the Italian Society of Rheumatology

Davide Rozza¹, Carlo Alberto Scirè^1|2, Paola Conigliaro³, Giacomo Emmi⁴, Laura Coladonato⁶, Salvatore Scarpato⁷, Luca Iaccarino⁸, Serena Guiducci⁹, Giulia Pazzola¹⁰, Francesca Romana Spinelli¹¹, Micol Frassi¹², Ilaria Cavazzana¹², Chiara Scirocco¹³, Valeria Orefice¹³, Immacolata Prevete¹³, Alessandra Bortoluzzi¹⁴, Marcello Govoni¹⁴, Elena Bartoloni¹⁵, Luca Moroni¹⁶, Giuseppe Alvise Ramirez¹⁶, Valentina Canti¹⁶, Giorgio Pettiti¹⁷, Maria Chiara Ditto¹⁸, Enrico Fusaro¹⁸, Marta Mosca¹⁹, Lorenzo Cavagna²⁰, Fabrizio Conti¹¹, Andrea Doria⁸, Gian Domenico Sebastiani¹³, Sperimentatori Gruppo Lire⁵ | ¹Centro Studi della Società Italiana di Reumatologia, Milano; ²Dipartimento di Medicina e Chirurgia, Università degli Studi di Milano-Bicocca, Monza; ³Università di Roma Tor Vergata; ⁴Dipartimento di Scienze Mediche, Chirurgiche e della Salute, Università di Trieste; ⁵https://redcap.reumatologia.it/surveys/?s=LWL7WJM4KHDR97CC; ⁶Dip di Medicina di Precisione e Rigenerativa e area Jonica, Bari; ⁷Azienda Sanitaria Locale ^ASL Salerno; ⁸Università degli Studi di Padova; ⁹SOD Reumatologia, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze; ¹⁰Arcispedale Santa Maria Nuova Reggio Emilia; ¹¹Università degli Studi di Roma La Sapienza; ¹²Spedali Civili di Brescia; ¹³Azienda Ospedaliera San Camillo Forlanini, Roma; ¹⁴Azienda Ospedaliera Universitaria Sant'Anna, Ferrara; ¹⁵SC Reumatologia, Dipartimento di Medicina e Chirurgia, Università di Perugia; ¹⁶IRCCS Ospedale San Raffaele, Milano; ¹⁷Azienda Ospedaliera S. Croce e Carle, Cuneo; ¹⁸AOU Citta' della Salute e della Scienza di Torino; ¹⁹AOU Santa Chiara, Pisa; ²⁰Università di Pavia, Italy

Background. The safety of biologic immunosuppressants in systemic lupus erythematosus (SLE) has been demonstrated in several interventional studies. However, estimates from unselected, real-world clinical populations remain scarce. This study aims to assess the safety of biologic immunosuppressants used as monotherapy (MONO-BIS) or in combination (COMB-BIS), compared to the exclusive use of non-biologic immunosuppressants (NBIS), in patients with SLE starting a new immunosuppressive treatment.

Materials and Methods. LIRE is a prospective, multicentre, pharmacoepidemiologic observational study promoted by the Italian Society of Rheumatology (SIR) (full list of investigators: https://redcap.reumatologia.it/surveys/?s=LWL7WJM4KHDR97CC). SLE patients who started a new immunosuppressive therapy between 2015 and 2022 were followed every six months for up to 5 years. Adverse events (AEs) were classified according to CTCAE v4.0 criteria and categorized as serious adverse events (SAEs), infections (INF), adverse events of special interest (AESI: infections, neoplasms, cardiovascular events), hospitalizations (HOSP), and deaths (DEA). Incidence rates and relative risks of AEs were estimated using weighted Cox models adjusted for baseline treatment indication. In addition to demographic factors, estimates were adjusted for anti-DNA antibody positivity, organ involvement (SLEDAI and/or BILAG), disease damage (SLICC-DI), disease activity (SLEDAI-2K), concomitant hydroxychloroquine use, and cumulative steroid dose (>10 g).

Results. Among the 338 included patients (87% women), 179 started NBIS, 55 MONO-BIS, and 104 COMB-BIS therapy. Belimumab (39%), rituximab (7%), mycophenolate (31%), and methotrexate (21%) were the most frequently used immunosuppressants. Infections were more frequent among BIS users (40%) compared to NBIS (18%), with higher rates in COMB-BIS (42%) than in MONO-BIS (35%). The COMB-BIS group had a higher prevalence of lupus nephritis (46%), higher cumulative corticosteroid exposure (>10 g prednisone equivalent: 58%), and a longer mean disease duration (12.6 years). The COMB-BIS group showed a significantly higher risk of AEs compared with NBIS (HR [95% CI]: 1.90 [1.29–2.79]), while the MONO-BIS group showed a non-significant increase (1.35 [0.76–2.40]). The risk of infections was significantly higher in COMB-BIS (2.82 [1.41–5.63]), and higher but not significantly so in MONO-BIS (2.49 [0.85–7.29]).

Conclusions. In this Italian real-world study, biologic drugs were associated with a higher risk of AEs when used in combination with NBIS, particularly infections occurring in the first months after treatment initiation. However, no relevant differences were found in serious adverse events (SAEs) or mortality within 24 months. These findings highlight that in patients with multi-organ involvement, the use of combined immunosuppressive therapy should be carefully evaluated and personalized according to individual clinical profiles, to balance therapeutic efficacy and the risk of adverse events.