Marco Sebastiani1, Vincenzo Venerito2, Serena Bugatti3, Chiara Bazzani4, Martina Biggioggero5, Luca Petricca6, Rosario Foti7, Alessandra Bortoluzzi8, Silvia Balduzzi3, Elisa Visalli7, Bruno Frediani9, Andreina Manfredi10, Elisa Gremese6, Ennio Favalli5, Florenzo Iannone2, Gianfranco Ferraccioli6, Giovanni Lapadula2. 1. Rheumatology Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico di Modena, Via del Pozzo, 41125, Modena, Italy. marco.sebastiani@unimore.it. 2. Department of Emergency and Organ Transplantation, Rheumatology Unit, University of Bari, Bari, Italy. 3. Division of Rheumatology, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy. 4. Unit of Rheumatology and Clinical Immunology, ASST Spedali Civili, Brescia, Italy. 5. Department of Rheumatology, Gaetano Pini Institute, Milan, Italy. 6. Division of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy. 7. Rheumatology Unit, A.O.U. Policlinico San Marco, Catania, Italy. 8. Section of Rheumatology, Department of Medical Sciences, University of Ferrara and Azienda Ospedaliera-Universitaria di Ferrara, Ferrara, Italy. 9. Rheumatology Unit, Department of Medical Sciences, Surgery e Neurosciences, University of Siena, Siena, Italy. 10. Rheumatology Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico di Modena, Via del Pozzo, 41125, Modena, Italy.
Abstract
OBJECTIVES: EULAR recommendations do not suggest which biologic disease-modifying anti-rheumatic drug (bDMARD) should be preferred after failure of a first bDMARD in the treatment of rheumatoid arthritis (RA). In particular, few data are available regarding the effectiveness of a second-line bDMARD after failure of abatacept (ABA), tocilizumab (TCZ), and rituximab (RTX). The aim of this study was to analyze the retention rate of a second line with tumor necrosis factor inhibitors (TNFi) or other mechanisms of action (MoAs), after the failure of either RTX, TCZ, or ABA. METHODS: Two hundred and seventy-eight RA patients from the Italian GISEA registry were included in the study. RTX was the first bDMARD in 18% of patients, ABA in 45.7%, and TCZ in 36.3%, while the second bDMARD was a TNFi (group 1) in 129 patients and an agent with a different MoA (group 2) in 149. RESULTS: During a median follow-up of 22 months (IQR 68), 129 patients discontinued their treatment; patients of group 1 discontinued the treatment more frequently than patients of group 2 (p<0.001) with retention rates of 33.6±5.7% and 63.6±4.6% after 104 weeks for group 1 and group 2, respectively (p<0.001). At multivariate analysis, the mechanism of action was the only predictor for the maintenance in therapy. CONCLUSIONS: According to our data, ABA, RTX, and TCZ seem to maintain a good retention rate also when used as a second-line therapy, suggesting their use after the failure of a non-TNFi as first-line therapy. However, specifically designed studies are needed to evaluate the more appropriate therapeutic strategies in RA, according to the first-line drug, including new targeted synthetic DMARDs. Key Points • A large proportion of rheumatoid arthritis patients fail the first biologic DMARD. • Few data are available about the efficacy of biologic DMARD after the failure of a non-TNF inhibitor. • Abatacept, rituximab, or tocilizumab seem to maintain a good retention rate after the failure of a first-course therapy with a non-TNF inhibitor.
OBJECTIVES: EULAR recommendations do not suggest which biologic disease-modifying anti-rheumatic drug (bDMARD) should be preferred after failure of a first bDMARD in the treatment of rheumatoid arthritis (RA). In particular, few data are available regarding the effectiveness of a second-line bDMARD after failure of abatacept (ABA), tocilizumab (TCZ), and rituximab (RTX). The aim of this study was to analyze the retention rate of a second line with tumor necrosis factor inhibitors (TNFi) or other mechanisms of action (MoAs), after the failure of either RTX, TCZ, or ABA. METHODS: Two hundred and seventy-eight RApatients from the Italian GISEA registry were included in the study. RTX was the first bDMARD in 18% of patients, ABA in 45.7%, and TCZ in 36.3%, while the second bDMARD was a TNFi (group 1) in 129 patients and an agent with a different MoA (group 2) in 149. RESULTS: During a median follow-up of 22 months (IQR 68), 129 patients discontinued their treatment; patients of group 1 discontinued the treatment more frequently than patients of group 2 (p<0.001) with retention rates of 33.6±5.7% and 63.6±4.6% after 104 weeks for group 1 and group 2, respectively (p<0.001). At multivariate analysis, the mechanism of action was the only predictor for the maintenance in therapy. CONCLUSIONS: According to our data, ABA, RTX, and TCZ seem to maintain a good retention rate also when used as a second-line therapy, suggesting their use after the failure of a non-TNFi as first-line therapy. However, specifically designed studies are needed to evaluate the more appropriate therapeutic strategies in RA, according to the first-line drug, including new targeted synthetic DMARDs. Key Points • A large proportion of rheumatoid arthritispatients fail the first biologic DMARD. • Few data are available about the efficacy of biologic DMARD after the failure of a non-TNF inhibitor. • Abatacept, rituximab, or tocilizumab seem to maintain a good retention rate after the failure of a first-course therapy with a non-TNF inhibitor.