PO:02:016 | Real-world evidence of upadacitinib over two years in Italian patients with axial spondyloarthritis

Mariagrazia Lorenzin¹, Giacomo Cozzi¹, Stefano Gentileschi², Michele Maria Luchetti Gentiloni³, Antonio Carletto⁴, Maria Sole Chimenti⁵, Maria Manara⁶, Luca Quartuccio⁷, Rosario Foti⁸, Salvatore D'Angelo⁹, Ariela Hoxha¹⁰, Carlo Selmi¹¹, Bernd Raffeiner¹², Alessandro Giollo¹, Alberto Cauli¹³, Carlo Salvarani¹⁴, Fabiola Atzeni¹⁵, Roberta Ramonda¹, Sir Study Group Spa E Psa Antonio Spadaro¹⁶. | ¹Rheumatology Unit, Department of Medicine DIMED, University of Padova, Padova, Italy; ²Rheumatology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; ³Clinica Medica, Ospedali Riuniti Ancona University Hospital, Ancona; Department of Clinical and Molecular Sciences, Ancona, Italy; ⁴Rheumatology Unit, Department of Medicine, AOUI University of Verona, Verona, Italy; ⁵Rheumatology, allergology and clinical Immunology, Department of Systems Medicine, University of Rome Tor Vergata, Roma, Italy; ⁶Humanitas San Pio X, Milano, Italy; ⁷University of Udine, Academic Hospital Santa Maria della Misericordia, Udine, Italy; ⁸Rheumatology Unit, A.O.U. Policlinico S. Marco, Catania, Italy; ⁹Rheumatology Department of Lucania, San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, Potenza, Italy; ¹⁰Internal Medicine Unit, Thrombotic and Hemorrhagic Center, Department of Medicine-DIMED, University of Padua, Padova, Italy; ¹¹Department of Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milano, Italy; ¹²Department of Rheumatology, Teaching Hospital of the Paracelsius Medical Hospital of Bolzano ASAA-SABES, Bolzano, Italy; ¹³Rheumatology Unit, Department of Medical Sciences, AOU and University of Cagliari, Monserrato, Cagliari, Italy; ¹⁴Department of Rheumatology, Azienda USL-IRCCS di Reggio Emilia and Università di Modena and Reggio Emilia, Reggio Emilia, Italy; ¹⁵Rheumatology Unit, University of Messina, Messina, Italy; ¹⁶Società Italiana di Reumatologia, Milano, Italy.

Background. This real-life investigation, conducted across multiple centres in Italy, aims to assess the 2-year effectiveness and safety of upadacitinib, a selective JAK1 inhibitor approved for the treatment of axial spondyloarthritis (axSpA). The study includes patients with both radiographic and non-radiographic axSpA and evaluates: (a) clinical outcomes at 6, 12, and 24 months; (b) drug retention rate (DRR); and (c) the influence of treatment line (LoBT), axSpA subtype, and sex on achieving low disease activity (LDA) and very low disease activity (VLDA). By analysing real-life clinical practice data, our analysis provides insight into the long-term therapeutic role of upadacitinib in managing axSpA, particularly in previously-treated patients or those with limited therapeutic options.

Methods. Consecutive patients with axSpA, who received upadacitinib between December 2022 and January 2025, were prospectively evaluated across multiple Italian centres. Data collected included baseline disease characteristics, comorbidities, prior and ongoing treatments, and follow-up duration. The primary endpoints were treatment effectiveness and safety, as well as drug retention rate (DRR), assessed at 6, 12, and 24 months from treatment initiation (T0). Effectiveness was evaluated using clinimetric indices, while safety outcomes included infections and adverse events (AEs). Secondary endpoints included the impact of biologic treatment history (bDMARDs), axSpA subtype (radiographic vs. non-radiographic), and sex on the achievement of low disease activity (LDA), defined as BASDAI <4 and/or ASDAS <2.1, and very low disease activity (VLDA), defined as BASDAI <2 and/or ASDAS <1.3, at each time point.

Results. A total of 203 patients were included in the analysis [48% male; median age at diagnosis: 44 years; 22.7% HLA-B27 positive -36.6% observed in Northern Italy); 71% with non-radiographic axSpA]. The median number of prior treatment lines was 3 (range: 1–12). At follow up, 170 patients were evaluable at 6 months (T6), 130 at T12 and 62 at T24. Overall, upadacitinib demonstrated a statistically significant improvement in effectiveness outcomes at 6 months, which was sustained over time at 12 and 24 months (Figure 1), regardless of LoBT, axSpA subtype, or sex. Of note, LDA at 24 months was more frequently achieved in the nr-axSpA subset (91.3% vs. 56.3%), while VLDA at 12 months was more commonly associated with female patients (41.5% vs. 21.4%). Remarkably, the DRR was consistently high throughout the observation period, with rates of 92%, 80%, and 55% recorded at 6, 12, and 24 months, respectively. Treatment was discontinued in 40 patients, with 22 cases attributed to primary or secondary loss of effectiveness and 2 cases due to adverse events.

Conclusions. Upadacitinib demonstrated a favourable safety and effectiveness profile across the axSpA population, regardless of prior treatment lines, axSpA subtype, or sex. Among evaluable patients sustained remission and consistent drug retention were observed over the two-year follow-up period.