Effectiveness and Predictors of Long-Term Treatment Response to Tofacitinib in Rheumatoid Arthritis Cohort: General Analysis and Focus on High-Cardiovascular-Risk Subgroup—A Multicenter Study

• Published in: Medicina (Kaunas, Lithuania) Lithuania), 2024-12, Vol.60 (12), p.1982
• Main Authors: Priora, Marta, Becciolini, Andrea, Celletti, Eleonora, Myriam Di Penta, Alberto Lo Gullo, Paroli, Marino, Bravi, Elena, Andracco, Romina, Nucera, Valeria, Ometto, Francesca, Lumetti, Federica, Farina, Antonella, Patrizia Del Medico, Colina, Matteo, Ravagnani, Viviana, Palma Scolieri, Larosa, Maddalena, Visalli, Elisa, Addimanda, Olga, Vitetta, Rosetta, Volpe, Alessandro, Bezzi, Alessandra, Girelli, Francesco, Aldo Biagio Molica Colella, Caccavale, Rosalba, Eleonora Di Donato, Adorni, Giuditta, Santilli, Daniele, Lucchini, Gianluca, Arrigoni, Eugenio, Sabatini, Emanuela, Platè, Ilaria, Mansueto, Natalia, Ianniello, Aurora, Fusaro, Enrico, Ditto, Maria Chiara, Bruzzese, Vincenzo, Camellino, Dario, Bianchi, Gerolamo, Serale, Francesca, Foti, Rosario, Amato, Giorgio, Francesco De Lucia, Ylenia Dal Bosco, Foti, Roberta, Reta, Massimo, Fiorenza, Alessia, Rovera, Guido, Marchetta, Antonio, Focherini, Maria Cristina, Mascella, Fabio, Bernardi, Simone, Sandri, Gilda, Giuggioli, Dilia, Salvarani, Carlo, Franchina, Veronica, Francesco Molica Colella, Ferrero, Giulio, Ariani, Alarico, Parisi, Simone
• Format: Article
• Language: English
• Subjects: Body mass index; Cancer; Cardiovascular disease; cardiovascular risk; Chronic illnesses; Clinical medicine; Diabetes; FDA approval; Hypertension; Kinases; Metabolic disorders; Patients; Performance evaluation; Remission (Medicine); Rheumatoid arthritis; Rheumatology; Risk factors; Steroids; Surveillance; tofacitinib
• ISSN: 1010-660X; 1648-9144
• DOI: 10.3390/medicina60121982

Background and Objectives: The treatment landscape for Rheumatoid Arthritis (RA) has evolved significantly with the introduction of Janus kinase inhibitors (JAKi), such as Tofacitinib (TOFA), which offer a new therapeutic option for patients who have failed or are intolerant to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Safety concerns, particularly related to cardiovascular and cancer risks, prompted a need for additional investigation in real-world clinical settings. This study aimed to evaluate the long-term effectiveness and predictors of response to TOFA in two subpopulations of RA patients, categorized by differing cardiovascular risk profiles. Materials and Methods: This was a retrospective, multicenter observational study conducted as part of the BIRRA project, involving 23 Italian rheumatological referral centers. A total of 213 patients diagnosed with RA and treated with TOFA were included, with data collected on baseline demographics, clinical history, disease activity, and comorbidities. Patients were divided into high-risk and low-risk cardiovascular groups based on age (≥65 years) and the presence of at least one cardiovascular risk factor. Disease activity was assessed at baseline, 6 months, and 12 months using DAS28-ESR and DAS28-CRP. Treatment response was evaluated using intention-to-treat (ITT) and per-protocol (PP) approaches. Predictors of low disease activity (LDA) and remission were assessed through logistic regression, and clustering analyses were used to identify subgroups of patients with different therapeutic responses. Results: The study included 213 patients, with 129 classified as high-risk. For the overall cohort, patients achieving LDA and remission at 6 months were 20% and 12%, respectively, for the ITT analysis, and 29% and 14% for the PP analysis. At 12 months, 26% of patients reached LDA, and 17% achieved remission according to ITT, while for the PP analysis, these rates were 30% and 19%, respectively. No significant differences in remission or LDA rates were observed between the high-risk and low-risk groups. In the high-risk subgroup, 17% of patients reached LDA and 9% achieved remission at 6 months (ITT analysis), while these rates increased to 22% and 13%, respectively, in the PP analysis. At 12 months, 22% achieved LDA and 13% achieved remission in the ITT analysis, while 28% and 17% did so in the PP analysis. The reduction in DAS28-ESR and DAS28-CRP scores was significant (p < 0.001) a