Real-world clinical experience with upadacitinib in a cohort of Italian patients with axial spondyloarthritis

Roberta Ramonda^1*Mariagrazia Lorenzin¹Antonio Carletto²Maria Sole Chimenti³Maria Manara⁴Giacomo Cozzi¹Alen Zabotti⁵Roberta Foti⁶Antonio Carriero⁷Ariela Hoxha⁸Carlo Selmi^10,9Bernd Raffeiner¹¹Alessandro Giollo¹Alberto Cauli¹²Carlo Salvarani¹³Fabiola Atzeni¹⁴Maurizio Rossini²Angelo Fassio²Francesca Nava²Valentino Paci¹⁵Gianluca Moroncini¹⁵Simona Buonanno¹⁶Bruno Frediani¹⁶Michele Maria Luchetti Gentiloni¹⁵Stefano Gentileschi¹⁶

• ¹Unit of Rheumatology, Department of Medicine, School of Medicine and Surgery, University of Padua, Padua, Italy
• ²Universita degli Studi di Verona, Verona, Italy
• ³Universita degli Studi di Roma Tor Vergata, Rome, Italy
• ⁴Azienda Socio Sanitaria Territoriale Gaetano Pini, Milan, Italy
• ⁵Universita degli Studi di Udine Dipartimento di Medicina, Udine, Italy
• ⁶Azienda Ospedaliero Universitaria Policlinico G Rodolico San Marco, Catania, Italy
• ⁷Azienda Ospedaliera Regionale San Carlo, Potenza, Italy
• ⁸Azienda Ospedale Universita Padova, Padua, Italy
• ⁹IRCCS Humanitas Research Hospital, Rozzano, Italy
• ¹⁰Humanitas University, Milan, Italy
• ¹¹Ospedale di Bolzano, Bolzano, Italy
• ¹²Universita degli Studi di Cagliari, Cagliari, Italy
• ¹³Universita degli Studi di Modena e Reggio Emilia, Modena, Italy
• ¹⁴Universita degli Studi di Messina, Messina, Italy
• ¹⁵Azienda Ospedaliero Universitaria delle Marche, Ancona, Italy
• ¹⁶Universita degli Studi di Siena, Siena, Italy

Background: There is currently scarce data on the real-world effectiveness and safety of upadacitinib in patients with axial spondyloarthritis (axSpA). This study evaluated clinical outcomes and drug retention rate (DRR) at 6, 12, and 24 months in patients initiating upadacitinib for axSpA. Methods: This prospective, observational study enrolled consecutive patients with radiographic axSpA (r-axSpA) or non-radiographic axSpA (nr-axSpA) initiating upadacitinib between December 2022 and January 2025 at 16 Italian centres. The primary endpoints were treatment effectiveness — evaluated using clinimetric indices, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) — safety and DRR at 6, 12, and 24 months. Results: Overall, 203 patients were analysed (48% male; median age at diagnosis 44 years; 22.7% HLA-B27 positive; 71% with nr-axSpA). Sixty-three patients completed the 24-month follow-up. Upadacitinib demonstrated a statistically significant improvement in effectiveness outcomes at six months vs. baseline, which was sustained at 12 and 24 months, regardless of previous biologic therapy lines, axSpA subtype, or sex. Furthermore, DRR was 92%, 80%, and 55% at six, 12, and 24 months, respectively. Forty patients discontinued upadacitinib, including 22 for insufficient effectiveness and two for AEs. Twenty-two patients developed infections. Conclusions: Upadacitinib demonstrated a favourable effectiveness profile in the evaluable axSpA population with sustained remission and high treatment retention over a two-year follow-up. Within the limitations inherent to this observational study, the tolerability profile of upadacitinib was generally consistent with that reported in randomized controlled trials, and no new safety signals were identified. Overall, these findings support the effectiveness of Janus kinase inhibitors in the treatment of patients with axSpA.