PO:01:010 | Survival of second-line treatment with TNF inhibitors vs. IL-23 inhibitors after failure of a first TNF inhibitor: a real-life observational study from the Italian multicenter BIRRA cohort in patients with psoriatic arthritis

Francesca Ometto¹, Olga Addimanda², Bernd Raffeiner³, Alberto Lo Gullo⁴, Elisa Visalli⁵, Eleonora Celletti⁶, Antonella Farina⁷, Maddalena Larosa⁸, Romina Andracco⁹, Marino Paroli¹⁰, Patrizia Del Medico¹¹, Aldo Biagio Molica Collella¹², Federica Lumetti¹³, Gilda Sandri¹⁴, Marta Priora¹⁵, Aurora Ianiello¹⁶, Elena Bravi¹⁷, Alessandra Bezzi¹⁸, Palma Scolieri¹⁹, Simone Parisi²⁰, Viviana Ravagnani²⁰, Rosetta Vitetta²⁰, Luca Idolazzi²⁰, Riccardo Bixio²⁰, Gianluca Santoboni²⁰, Francesco Girelli²⁰, Alarico Ariani²⁰ | ¹Azienda ULSS 6 Euganea, Padova; ²UOC Interaziendale di Medicina Interna ad Indirizzo Reumatologico, AUSL BO - IRCCS AOU Bologna; ³Unità di Reumatologia, Teaching Hospital of the Paracelsius Medical University, Central Hospital of Bolzano (ASAA-SABES) Bolzano; ⁴UOD Reumatologia, ARNAS Garibaldi Catania; ⁵UO Reumatologia, Policlinico San Marco Hospital Catania; ⁶UOS Reumatologia, Ospedale SS. Annunziata, Università G. d'Annunzio, Chieti; ⁷UOC Medicina Interna- Ambulatorio Reumatologico, Ospedale A. Murri, Fermo; ⁸S.C. Reumatologia, Dipartimento Specialità Mediche, Ospedale La Colletta-Azienda Sanitaria Locale 3 Genova; ⁹Ambulatorio Reumatologia, Ospedale di Imperia; ¹⁰Sapienza Università Polo Pontino, Latina; ¹¹Ambulatorio di Reumatologia, UO Medicina Interna, Civitanova Marche Hospital, Civitanova (MC); ¹²UOSD di Reumatologia, Azienda Ospedaliera Papardo Messina; ¹³Unità di Reumatologia, Azienda USL di Modena e Ospedale Universitario Policlinico di Modena; ¹⁴Unità di Reumatologia, Università di Modena e Reggio Emilia Modena; ¹⁵Ambulatorio e Day Hospital di Reumatologia, ASL CN1, Mondovì (CN); ¹⁶Poliambulatorio specialistico di reumatologia e Day Hospital multidisciplinare di area Medica, ASL Novara; ¹⁷UOSD Reumatologia, Ospedale G. Da Saliceto, Piacenza; ¹⁸UO Medicina Interna e Reumatologia, SS Reumatologia, ASL Romagna, Rimini; ¹⁹UOC Medicina Interna e Reumatologia, Ospedale Nuovo Regina Margherita, Roma; ²⁰Gruppo BIRRA Italy

Background. Since 2021, IL-23 inhibitors (IL-23i) such as guselkumab, and since 2022 risankizumab, have been available for the treatment of psoriatic arthritis (PsA). However, after failure of a first tumor necrosis factor inhibitor (TNFi), switching to a second TNFi remains common. This study aims to compare second-line drug survival between “cycling” (second TNFi) and “swapping” (IL-23i) in Italian real-life clinical practice.

Materials and Methods. A multicenter retrospective observational study was conducted on PsA patients treated with second-line TNFi or IL-23i. Drug survival was analyzed using Cox regression, considering age, sex, disease duration and domains (peripheral, axial, or mixed), disease activity, year of prescription, concomitant use of DMARDs or corticosteroids, and type of second-line treatment.

Results. A total of 269 patients were included (62.8% female; median age 56.0 [47.0–64.0] years), of whom 191 (71.0%) were treated with TNFi and 78 (29.0%) with IL-23i (70 with guselkumab and 8 with risankizumab). Compared with patients receiving a second TNFi, those treated with IL-23i had more severe disease at treatment initiation (longer disease duration and higher DAPSA scores) (Figure 1A). A more recent year of prescription was significantly associated with reduced drug survival, with an approximately ninefold increased relative risk per year (HR 9.17 [5.52–15.24], p<0.001). Mixed (axial and peripheral) PsA was associated with a higher risk of treatment failure compared with peripheral PsA (HR 2.94 [1.64–5.29], p<0.001). Use of IL-23i as second-line therapy was associated with a 91% lower risk of failure compared with TNFi (HR 0.09 [0.04–0.24], p<0.001) (Figure 1B). When including disease activity (DAPSA) and restricting the analysis to patients with peripheral or mixed PsA, the significant variables remained largely unchanged: year of prescription (HR 14.44 [7.32–28.49], p<0.001); axial and peripheral vs peripheral PsA (HR 2.71 [1.39–5.27], p=0.003); IL-23i vs TNFi (HR 0.10 [0.03–0.31], p<0.001); while disease activity had no effect on drug survival (HR 0.98 [0.96–1.01], p=0.166).

Conclusions. The recent availability of multiple therapeutic options has led to reduced treatment survival, likely reflecting improved clinical management of patients with PsA. Switching to an IL-23 inhibitor after failure of a TNFi is associated with greater effectiveness compared with cycling to a second TNFi, even in patients with more severe disease and regardless of PsA clinical activity. Longer follow-up studies are needed to confirm these findings and to assess potential differences within the IL-23 inhibitor class.