FRI0219 Risk Factors of Severe Infections in Patients with Rheumatoid Arthritis Treated with Tocilizumab in The French Registry Regate (Registry –Roactemra)
Authors: J. Morel, A. Constantin, E. Dernis, S. Rist, R.M. Flipo, T. Schaeverbeke, O. Vittecoq, M. Soubrier, A. Saraux, B. Combe, M. Dougados, A. Pinta, G. Baron, J.-E. Gottenberg, X. Mariette, P. Ravaud, J. Sibilia
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Observational studies have already reported the risk of severe infections in rheumatoid arthritis (RA) treated with tocilizumab but in limited samples. <h3>Objectives</h3> The aim of this study was to investigate the predictive risk factors of severe infections in the largest European registry of patients treated with tocilizumab for RA. <h3>Methods</h3> 1491 RA patients included in the French REGistry –RoAcTEmra (REGATE) were analysed to calculate incidence rate of severe infections and to identify independent factors associated with severe infections. Kaplan -Meier method was used to assess probability of remaining severe infection-free. Cox models were performed to identify independent factors associated with severe infections. Variables showing bivariate association with the dependent variable with a <i>P</i> value less than 0.15 were entered into the multivariate model. Multiple imputation was used to compensate missing data in some variables. A <i>P</i> value &lt;0.05 was considered statistically significant. <h3>Results</h3> Exposure was 2,606 person-years (mean age±SD, 56.6±13.6). 125 serious infections occurred in 122 patients (4.7/100 patient-years). Most frequent infections were lung and respiratory tract and skin/soft tissue in 35 (28%) and 32 (26%) cases respectively. Three deaths were related to one septic chock secondary to pyelonephritis, one pneumocystosis, and one <i>Haemophilus influenzae</i> infection. Favourable outcome was observed in most cases. Four opportunistic infections were reported: 1 Pneumocystosis, 1 tuberculosis, 1 <i>Haemophilus influenzae</i> infection and 1 infection related to <i>Klebsiella pneumoniae</i>. A pathogen was identified in 41 cases. TCZ was definitively stopped for 35 patients. The incidence of serious infection was stable over the first 3 years of follow-up in the registry. Bivariate analysis identified initial ACPA positivity as the only factor associated with a lower risk of severe infection (HR 0.55 CI95% 0.35–0.86). Factors significantly associated with a risk of severe infections were DAS28-CRP, DAS28-ESR, and number of polymorphonuclear neutrophils (PMN) at baseline. Initial PMN above 4.5 G/L (HR 1.62 CI95% 1.06–2.5, p=0.02) and negative ACPA (HR 0.63 CI95% 0.41–0.95, p=0.03) remains significantly associated with severe infections in multivariate analysis after imputation for missing data. <h3>Conclusions</h3> The rate of severe infections in current practice is similar to that reported in clinical trials. High PMN above 4.5 G/L at baseline and negative ACPA are predictive factors of serious infection requiring in this case a tighter surveillance. <h3>Acknowledgement</h3> The French registry REGATE was supported by an unrestricted grant of Roche Chugaï. We thank Isabelle Pane for assistance with database management. <h3>Disclosure of Interest</h3> J. Morel Consultant for: ROCHE CHUGAI, NORDIC PHARMA, A. Constantin Consultant for: ROCHE CHUGAI, Speakers bureau: NORDIC PHARMA, E. Dernis: None declared, S. Rist Speakers bureau: ROCHE CHUGAI, R. M. Flipo Consultant for: ROCHE CHUGAI, NORDIC PHARMA, Speakers bureau: ROCHE CHUGAI, NORDIC PHARMA, T. Schaeverbeke Consultant for: ROCHE CHUGAI, NORDIC PHARMA, Speakers bureau: ROCHE CHUGAI, NORDIC PHARMA, O. Vittecoq Speakers bureau: ROCHE CHUGAI, M. Soubrier: None declared, A. Saraux Grant/research support from: ROCHE CHUGAI, Consultant for: ROCHE CHUGAI, Speakers bureau: ROCHE CHUGAI, B. Combe Consultant for: ROCHE CHUGAI, Speakers bureau: ROCHE CHUGAI, M. Dougados Consultant for: ROCHE CHUGAI, Speakers bureau: ROCHE CHUGAI, A. Pinta Employee of: ROCHE CHUGAI, G. Baron: None declared, J.-E. Gottenberg: None declared, X. Mariette: None declared, P. Ravaud: None declared, J. Sibilia Consultant for: ROCHE CHUGAI, Speakers bureau: ROCHE CHUGAI