PO:01:004 | Real-world retention of IL-17 inhibitors in psoriatic arthritis: impact of prior IL-17 exposure across multiple treatment lines in the “birra” multicentre cohort

Valentino Paci¹, Alarico Ariani², Eleonora Celletti³, Alberto Lo Gullo⁴, Camilla Mazzanti⁵, Valeria Nucera⁶, Natalia Mansueto⁷, Rosalba Caccavale⁸, Patrizia Del Medico⁹, Antonella Farina¹⁰, Palma Scolieri¹¹, Cecilia Giampietro¹², Olga Addimanda¹³, Riccardo Bixio¹⁴, Maddalena Larosa¹⁵, Viviana Ravagnani¹⁶, Federica Lumetti¹⁷, Aldo Biagio Molica Colella¹⁷, Elena Bravi¹⁷, Rosetta Vitetta¹⁷, Bernd Raffeiner¹⁷, Gilda Sandri¹⁸, Rosario Foti¹⁹, Simone Parisi²⁰, Michele Maria Luchetti Gentiloni¹, Gianluca Moroncini¹. | ¹Clinical Medicine, Department of Clinical and Molecular Sciences, Marche Polytechnic University, AOU delle Marche, Ancona; ²Internal Medicine and Rheumatology Unit, University Hospital of Parma, Parma; ³Rheumatology Unit, Clinica Medica Institute, Ospedale SS. Annunziata di Chieti, G.d'Annunzio University of Chieti, Chieti; ⁴Rheumatology Unit, ARNAS Garibaldi di Catania, Catania; ⁵Center for the Diagnosis and Therapy of Autoimmune Rheumagological Diseases, Ospedale Santa Rosa, ASL Viterbo, Viterbo; ⁶Rheumatology Outpatient Unit, ASL Novara, Novara; ⁷Ambulatori di Reumatologia ASL1 Liguria, Imperia Hospitall, Imperia; ⁸Department of Clinical, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Polo Pontino, Roma; ⁹Rheumatology outpatient clinic - Internal Medicine Unit, Civitanova, Marche Hospital, Civitanova, Marche; ¹⁰Internal Medicine Unit, Rheumatology outpatient clinic, Ospedale A. Murri di Fermo Fermo; ¹¹Department of Medical Specialties, Nuovo Regina Margherita Hospital, Roma; ¹²Rheumatology Outpatient Clinic, Azienda ULSS 6 Euganea, Padova, Padova; ¹³Rheumatology Unit, Azienda Unità Sanitaria Locale di Bologna -- Policlinico S.Orsola- AOU di Bologna, Bologna; ¹⁴Rheumatology Unit, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, Verona; ¹⁵Division of Rheumatology - Medical Specialties Department, Ospedale La Colletta-Azienda Sanitaria Locale 3 Genova; ¹⁶Rheumatology Unit, Santa Chiara Hospital APSS Trento; ¹⁷BIRRA - BIologic Retention Rate in chronic Arthritis - study group Parma; ¹⁸Rheumatology Unit, University of Modena and Reggio Emilia, Modena; ¹⁹Rheumatology Unit, Policlinico San Marco Hospital, Catania; ²⁰Rheumatology Department, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.

AIM OF THE STUDY. Several studies have explored cycling versus switching strategies in Psoriatic Arthritis (PsA) when TNF-alpha inhibitors are used as biological DMARD (bDMARD). Conversely, real-world evidence regarding cycling strategies within other bDMARD classes is lacking. In this study, we aimed to evaluate the retention rate of interleukin-17 inhibitors (anti-IL17) in patients with PsA, focusing on the differences between those receiving their first anti-IL17 agent and those previously exposed to anti-IL17 therapy.

METHODS This was a multicentre, retrospective, observational study. All consecutive patients with PsA treated with an anti-IL17 bDMARD were included. The baseline assessment encompassed demographic and clinical characteristics, including disease domains and activity scores, IL-17 exposure status, number of prior bDMARD lines, and concomitant therapies. The primary outcomes were: a. the retention rate of anti-IL17 agents in IL-17 naïve versus IL-17 experienced patients; b. predictors of treatment discontinuation.

RESULTS. A total of 868 patients were included (59.3% female; median age 56 [48-63] years). The majority were receiving their first anti-IL17 agent (89.3% IL17 naïve vs 10.7% IL17 experienced). Secukinumab was the most frequently prescribed bDMARD (70.8%), followed by Ixekizumab (28.6%), and Bimekizumab (0.6%) (Figure 1.A.). At baseline, IL17 experienced patients more commonly exhibited axial involvement compared to IL17 naïve patients (59.1% vs 35.4%) and had received a higher median number of previous bDMARDs (4 [3-5] vs 2 [1-3] lines, respectively). Secukinumab was more frequently prescribed in IL17 naïve patients (76.9% vs 20.4%), whereas Ixekizumab was preferentially used in IL17 experienced individuals (Figure 1.A.). Median follow-up for the overall cohort was 15.2 [7.0-33.8] months, for a total exposure of 20’014 patient-months. At 12 months, the estimated retention rate was 77.6% vs 77.0% in naïve vs experienced patients respectively, dropping at 61.7% vs 54.0% at 24 months. Although Kaplan–Meier curves suggested a numerically lower persistence among IL17 experienced cases, this difference did not reach statistical significance (log-rank p = 0.068) (Figure 1.B.). In multivariable Cox regression analysis, male gender, a lower number of prior bDMARDs, and treatment with Secukinumab were associated with higher odds of drug survival, whereas axial involvement increased the risk of discontinuation. Prior IL17 exposure was associated with a non-significant trend towards a lower risk of discontinuation (Figure 1.C.).

CONCLUSION. Our findings suggest that, in the real-world PsA clinical practice, prior exposure to an IL17 inhibitor may not compromise the retention of a subsequent agent from the same class. Conversely, drug survival was influenced by gender, axial involvement, the specific bDMARD prescribed, and the cumulative number of prior bDMARDs. Recycling within the IL17 inhibitor class may represent an effective strategy. Nevertheless, further studies are warranted to better define the clinical contexts in which this approach could be most appropriate.