Jacques Morel1, Arnaud Constantin2, Gabriel Baron3, Emmanuelle Dernis4, René Marc Flipo5, Stéphanie Rist6, Bernard Combe1, Jacques Eric Gottenberg7, Thierry Schaeverbeke8, Martin Soubrier9, Olivier Vittecoq10, Maxime Dougados11, Alain Saraux12, Xavier Mariette13, Philippe Ravaud3, Jean Sibilia7. 1. Department of Rheumatology, Teaching Hospital Lapeyronie, University of Montpellier, Montpellier. 2. Department of Rheumatology, Teaching Hospital Purpan, and University of Paul Sabatier, Toulouse. 3. Centre de Recherche en Epidémiologie et Statistiques, INSERM U1153, Centre d'Épidémiologie Clinique, Hôpital Hôtel-Dieu, Assistance Publique-Hôpitaux de Paris (AP-HP), Descartes University, Paris. 4. Department of Rheumatology, Hospital Le Mans, Le Mans. 5. Department of Rheumatology, Teaching Hospital, and University of Lille 2, Lille. 6. Department of Rheumatology, Hospital Orléans, Orléans. 7. Department of Rheumatology, Teaching Hospital, University of Strasbourg, Strasbourg. 8. Department of Rheumatology, Teaching Hospital Pellegrin, University of Bordeaux, Bordeaux. 9. Department of Rheumatology, Teaching Hospital, University of Clermont-Ferrand, Clermont-Ferrand. 10. Department of Rheumatology, Teaching Hospital, University of Rouen, Inserm 905, Rouen. 11. Department of Rheumatology, Teaching Hospital Cochin, University of Paris Descartes, Paris. 12. Department of Rheumatology, Teaching Hospital, University of Brest, Brest. 13. Department of Rheumatology, Hôpitaux Universitaires, and University of Paris Sud U1184, Center of Immunology of Viral Infections, Auto-immune Diseases, Paris, France.
Abstract
Objectives: Observational studies have already reported the risk of serious infections in RA treated with tocilizumab, but in limited samples. The aim of this study was to investigate the predictive risk factors for serious infections in the largest European registry of patients treated with tocilizumab for RA. Methods: A total of 1491 RA patients included in the French REGistry-RoAcTEmra were analysed to calculate the incidence rate of first serious infections rate after initiation of tocilizumab. To identify independent factors associated with serious infections, a Cox model was performed. Results: Among the 1491 patients, average age 56.6 (13.6) years, 125 serious infections occurred in 122 patients (incidence rate of serious infection: 4.7/100 patient-years). Univariate analysis identified initial ACPA positivity as the only factor associated with a lower risk of serious infection [hazard ratio (HR) = 0.56, 95% CI: 0.36, 0.88]. Other factors significantly associated with a higher risk of serious infections were DAS28, concomitant Leflunomide (LEF) treatment, and absolute neutrophil count (ANC) at baseline. Initial ANC above 5.0 × 109/l (HR = 1.94, 95% CI: 1.32, 2.85; P < 0.001), negative ACPA (HR = 1.79, 95% CI: 1.15, 2.78; P = 0.012) at baseline and concomitant LEF treatment (LEF alone vs no treatment, HR = 2.18, 95% CI: 1.22, 3.88; P = 0.009) remained significantly associated with first serious infections in multivariate analysis after imputation for missing data. Conclusion: The rate of first serious infections in current practice is similar to that reported in clinical trials. High ANC (above 5.0 × 109 at baseline), negative ACPA and concomitant therapy with LEF are predictive factors of serious infection, requiring in this case a tighter surveillance.
Objectives: Observational studies have already reported the risk of serious infections in RA treated with tocilizumab, but in limited samples. The aim of this study was to investigate the predictive risk factors for serious infections in the largest European registry of patients treated with tocilizumab for RA. Methods: A total of 1491 RApatients included in the French REGistry-RoAcTEmra were analysed to calculate the incidence rate of first serious infections rate after initiation of tocilizumab. To identify independent factors associated with serious infections, a Cox model was performed. Results: Among the 1491 patients, average age 56.6 (13.6) years, 125 serious infections occurred in 122 patients (incidence rate of serious infection: 4.7/100 patient-years). Univariate analysis identified initial ACPA positivity as the only factor associated with a lower risk of serious infection [hazard ratio (HR) = 0.56, 95% CI: 0.36, 0.88]. Other factors significantly associated with a higher risk of serious infections were DAS28, concomitant Leflunomide (LEF) treatment, and absolute neutrophil count (ANC) at baseline. Initial ANC above 5.0 × 109/l (HR = 1.94, 95% CI: 1.32, 2.85; P < 0.001), negative ACPA (HR = 1.79, 95% CI: 1.15, 2.78; P = 0.012) at baseline and concomitant LEF treatment (LEF alone vs no treatment, HR = 2.18, 95% CI: 1.22, 3.88; P = 0.009) remained significantly associated with first serious infections in multivariate analysis after imputation for missing data. Conclusion: The rate of first serious infections in current practice is similar to that reported in clinical trials. High ANC (above 5.0 × 109 at baseline), negative ACPA and concomitant therapy with LEF are predictive factors of serious infection, requiring in this case a tighter surveillance.
Authors: Víctor Moreno-Torres; Carmen de Mendoza; Sara de la Fuente; Enrique Sánchez; María Martínez-Urbistondo; Jesús Herráiz; Andrea Gutiérrez; Ángela Gutiérrez; Carlos Hernández; Alejandro Callejas; Carmen Maínez; Ana Royuela; Valentín Cuervas-Mons Journal: Intern Emerg Med Date: 2021-08-18 Impact factor: 5.472
Authors: Ernest H Choy; Fabrizio De Benedetti; Tsutomu Takeuchi; Misato Hashizume; Markus R John; Tadamitsu Kishimoto Journal: Nat Rev Rheumatol Date: 2020-04-23 Impact factor: 20.543
Authors: Diana Prieto-Peña; Pilar Bernabeu; Paloma Vela; Javier Narváez; Jesús C Fernández-López; Mercedes Freire-González; Beatriz González-Álvarez; Roser Solans-Laqué; José L Callejas Rubio; Norberto Ortego; Carlos Fernández-Díaz; Esteban Rubio; Salvador García-Morillo; Mauricio Minguez; Cristina Fernández-Carballido; Eugenio de Miguel; Sheila Melchor; Eva Salgado; Beatriz Bravo; Susana Romero-Yuste; Juan Salvatierra; Cristina Hidalgo; Sara Manrique; Carlos Romero-Gómez; Patricia Moya; Noelia Álvarez-Rivas; Javier Mendizabal; Francisco Ortiz-Sanjuán; Iván Pérez de Pedro; José L Alonso-Valdivielso; Laura Perez-Sanchez; Rosa Roldán; Nagore Fernandez-Llanio; Ricardo Gómez de la Torre; Silvia Suarez; María Jesús Montesa Cabrera; Mónica Delgado Sánchez; Javier Loricera; Belén Atienza-Mateo; Santos Castañeda; Miguel A González-Gay; Ricardo Blanco Journal: Ther Adv Musculoskelet Dis Date: 2021-06-18 Impact factor: 5.346