Guselkumab effectiveness in real-world settings: Observations from an Italian multicentre study

Objectives: Guselkumab is a biologic disease-modifying antirheumatic drug (bDMARD) with proven efficacy for psoriatic arthritis (PsA) in randomized controlled trials. Evidence of its effectiveness from clinical practice remains limited. We evaluated the real-world effectiveness of guselkumab for PsA (primary objective) and identified factors influencing clinical outcomes. Methods: This retrospective, observational, multicentre study enrolled consecutive patients with PsA prescribed guselkumab for joint involvement at 26 Italian rheumatology referral centres. Baseline data included patient history, PsA subtype, treatment history and disease activity. Treatment effectiveness was assessed with Kaplan-Meier curves; Cox proportional hazards analysis identified factors associated with treatment persistence. Results: The study included 278 patients (median age: 57 years [interquartile range, IQR: 50-63]; 64.4% female); median observation 10.7 months (IQR: 5.3-15.9; total: 3332.6 patient-months). Retention rates at 6, 12 and 24 months were 90.4%, 80.0% and 67.8%, respectively. Reasons for discontinuation included primary inefficacy (48% of 54 cases), secondary inefficacy (41%) and skin/mucosal intolerance (4%). Statistically significant factors (P < 0.05) influencing treatment persistence included sex, smoking, concurrent conventional synthetic DMARDs (csDMARDs), corticosteroid use, year of prescription and axial or enthesitic involvement. Conclusions: Approximately two-thirds of PsA patients treated with guselkumab remained on therapy after 2 years. Adverse events motivated <10% of discontinuations. Effectiveness was higher in patients with enthesitic or axial PsA and in those without concurrent corticosteroids or csDMARDs, confirming the effectiveness and safety of guselkumab as an optimal choice for monotherapy, particularly in PsA patients with enthesitis, with or without joint impairment, and/or axial involvement. Lay Summary What does this mean for patients? This study looked at how well the biologic drug guselkumab works in everyday clinical practice for people living with psoriatic arthritis (PsA), a chronic inflammatory disease that affects the joints and skin. We collected data from 278 patients treated at 26 rheumatology centres in Italy. Unlike clinical trials, which enrol patients who meet selective criteria, this study reflects what happens in the real world. We found that most patients had continued taking guselkumab over time: after 1 year, 80% were still on treatment, and after 2 years, about 68% remained on it. The main reasons people stopped the drug were because it did not work well enough initially, or it stopped working over time. Side effects were rare and mild. Patients with inflammation near tendons or ligaments (enthesitis), or those with spinal involvement (axial PsA) had the best results. In contrast, those taking other medications like steroids or methotrexate along with guselkumab were more likely to stop treatment early. These findings suggest that guselkumab is a safe and effective long-term treatment option for people with PsA, especially those with enthesitis or spinal involvement. The findings support its use as a standalone therapy in appropriate patients and help guide real-world treatment decisions.