POS0611 ONE YEAR PERSISTENCE AND EFFECTIVENESS OF GUSELKUMAB OR TNFi AS SECOND-LINE TREATMENT AFTER RECEIVING A TNFi AS FIRST-LINE THERAPY TO TREAT ACTIVE PSORIATIC ARTHRITIS: MANHATTAN STUDY

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Background: Psoriatic Arthritis (PsA) is a heterogeneous condition that can involve different domains such as peripheral arthritis, enthesis, dactylitis, axial disease, skin psoriasis or nail psoriasis. In recent years, there has been substantial expansion in treatment options and therapeutic approaches. In Spain, tumor necrosis factor inhibitors (TNFis) are the most commonly used drugs in the first-line of biological treatment mostly due to the good efficacy/safety balance and financing conditions. Nevertheless, there is limited data on the sequencing of biological therapies in terms of treatment effectiveness and drug persistence. Objectives: The objective of the MANHATTAN study (CNTO1959PSA4009) was to evaluate the persistence, effectiveness, and tolerability of guselkumab (GUS), an anti-IL-23 agent, compared to a second TNFi in adults with PsA who had failed to a prior TNFi as first-line therapy. Methods: MANHATTAN is an ongoing ambispective, observational study across 35 Spanish hospitals. It included patients with PsA who had previously used a TNFi and switched to GUS or another TNFi as second-line therapy. Of the 144 patients enrolled, 139 were analyzed: 77 on GUS and 62 on TNFi. Baseline characteristics, prior first-line treatments, and concomitant medications were recorded. Study endpoints included treatment persistence (analyzed by Kaplan-Meier curves), the percentage of patients achieving minimal disease activity (MDA), the description of the psoriatic body surface area (BSA), and the mean change in tender joint count (TJC) and swollen joint count (SJC). Interim results up to week 52 are presented. Results: Demographic characteristics were comparable among GUS and TNFi groups. The proportion of females was 59.7% and 50.0%, respectively. The mean age at PsA diagnosis was 43.9 and 44.7 years, while mean BMI was 28.2 kg/m 2 and 27.3 kg/m 2 , respectively. The most predominant PsA pattern was polyarticular PsA (62.3%, 66.1%), oligoarticular PsA (31.6%, 29.5%), enthesitis (21.1%, 37.1%), dactylitis (15.8% and 18.0%), nail psoriasis (38.2%, 36.1%), and active skin psoriasis (66.2%, 47.5%), respectively. At week 0, the Disease Activity in Psoriatic Arthritis (DAPSA) scores were 23 (GUS) and 21.2 (TNFi), while the mean psoriatic BSA was 4% for GUS and 1.9% for TNFi groups. The mean TJC was 6.0 and 5.5 for GUS and TNFi; and mean SJC was 3.5 and 2.9, respectively. In the GUS group, 62.3% of the patients had some type of comorbidity, versus 66.1% in the TNFi patients. The most common first-line TNFi was adalimumab (69.8%), followed by etanercept (22.3%), and certolizumab (5.0%). Regarding second-line TNFi, the most predominant was etanercept (46.8%), followed by adalimumab (25.8%), and golimumab (14.5%). Concomitant conventional disease-modifying antirheumatic drugs were used in 41.6% of second-line GUS patients and 41.9% of second-line TNFi patients. Up to week 52, the persistence (analyzed by Kaplan-Meier curves) was longer in patients on GUS than those on TNFi (85.3% and 73.5%, respectively) (Figure 1). The overall percentage of patients who achieved MDA gradually increased over time, with 30.0% progressing at week 12, 42.0% at week 24, and 48.0% at week 52 in the GUS group. In the TNFi group, 26.0%, 31.4% and 43.8% progressed to MDA at weeks 12, 24 and 52, respectively. Therefore, a slightly higher proportion was observed achieving MDA in the GUS group at all time points (Figure 2). Improvements in BSA were noted for GUS, showing an absolute mean change from week 0 of -2.6 at week 12, -3.2 at week 24, and -4.9 at week 52. A minor decrease was observed for those with second-line TNFi (-0.4, -0.8, and -0.4, at weeks 12, 24, and 52, respectively). Finally, TJC decreased over time in both groups showing an absolute mean change of -2.7 at week 12, -3.3 at week 24, and -3.2 at week 52 for GUS; and -2.2, -3.5, and -3.8; at weeks 12, 24, and 52, respectively for TNFi. A similar decrease was observed in the SJCs (-2.0, -1.9, and -2.2; at weeks 12, 24, and 52, respectively for GUS; and -1.6, -2.4, and -3.1; at weeks 12, 24, and 52, respectively for TNFi patients). Conclusion: Second-line GUS showed higher persistence and lower discontinuation rates at week 52 than second-line TNFi, indicating sustained patient effectiveness, adherence, and tolerability. Second-line GUS also demonstrated effectiveness in reducing PsA disease activity, with higher proportion of patients achieving MDA and improvements in BSA than the second-line TNFi group. These findings suggest that GUS is an effective and durable alternative for second-line PsA treatment. REFERENCES: NIL . Figure 1Kaplan-Meier plot of second-line treatment (GUS or TNFi) persistence up to week 52. Figure 2Percentage of patients achieving minimal disease activity (MDA) in second-line treatment (GUS or TNFi) at week 0, week 12, 24 and 52. MDA was achieved if 5 of 7 criteria were met: TJC ≤1; SJC ≤1; BSA ≤ 3%; patient's assessment of pain by visual analogue scale (VAS) ≤15 mm; patient's global assessment of disease activity by VAS ≤20 mm; Health Assessment Questionnaire ≤0.5; and tender entheseal points ≤ 1 (assessed by the Leeds Enthesitis Index). Acknowledgements: NIL . Disclosure of Interests: Beatriz Joven-Ibáñez: None declared, MARIA ROCIO GONZALEZ MOLINA: None declared, María Vanesa Hernández Hernández: None declared, Marta Llanes: None declared, Carolina Marin-Huertas: None declared, Lourdes Mateo: None declared, ELENA ALONSO MORALES: None declared, Laura Nuño: None declared, Meritxell Sallés Lizarzaburu: None declared, Manuel Moreno: None declared, Martina Steiner: None declared, Antonio Fernández-Nebro: None declared, Elisabet Garcia Casares: None declared, ANGELES HERNANDEZ DEL RIO: None declared, Janire Malave Calzada: None declared, Lola Fernandez de la Fuente Burson: None declared, Laia Orpinell: None declared, Raúl Veroz González: None declared, Evelin Cecilia Cervantes Pérez: None declared, Sonia Castro Oreiro: None declared, Ana Urruticoechea-Arana: None declared, Inmaculada Ros: None declared, Patricia López Viejo: None declared, Oscar Camacho: None declared, EMILIO GINER: None declared, Luis Sarabia de Ardanaz: None declared, Alba Erra: None declared, MARIA DELPUERTO MORENO GIL: None declared, Francisco Maceiras-Pan: None declared, JORGE CABEZON DOMINGUEZ: None declared, Daniel Pielfort: None declared, Manuel Cuervas-Mons Johnson & Johnson, Sabela Díaz-Castroverde Vicario Johnson & Johnson, Santiago Munoz-Fernández: None declared, Julio Ramirez: None declared, Jose Antonio Pinto Tasende: None declared. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

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