Risk Factors of Severe Infections in Patients with Rheumatoid Arthritis Treated with Tocilizumab in the French Registry Regate (REGISTRY –ROACTEMRA)

Jacques Morel^1,2, Arnaud CONSTANTIN³, Gabriel Baron⁴, Emmanuelle Dernis⁵, Rene-Marc Flipo^6,7, Stephanie Rist Bouillon⁸, Bernard Combe⁹, Jacques-Eric Gottenberg¹⁰, Thierry Schaeverbeke^11,12, Martin Soubrier¹³, Olivier Vittecoq¹⁴, Maxime Dougados¹⁵, Alain Saraux¹⁶, Xavier Mariette¹⁷, Philippe Ravaud¹⁸ and Jean Sibilia¹⁹, ¹Montpellier University Hospital, Montpellier, France, ²Department of Rheumatology, Hôpital Lapeyronie, Montpellier, France, ³Rheumatology, CHU Purpan - Hôpital Pierre-Paul Riquet, Toulouse, France, ⁴Hôpital Hôtel Dieu, Paris, France, ⁵Service de Rhumatologie, Centre Hospitalier, Le Mans, France, ⁶Rheumatology, Hopital R Salengro CHRU, Lille, France, ⁷Rheumatology, University Hospital, Lille, France, ⁸Rhumatologie, Hopital La Source, La Source, France, ⁹Département Rhumatologie, Hôpital Lapeyronie, Montpellier, France, ¹⁰Department of Rheumatology, Strasbourg University Hospital, Strasbourg, France, ¹¹Bordeaux University Hospital, Bordeaux, France, ¹²Rheumatology, CHU Bordeaux, Bordeaux, France, ¹³Rheumatology, Department of Rheumatology, CHU Gabriel Montpied, Clermont-Ferrand, France, ¹⁴Rheumatology, Rouen University Hospital &INSERM U905, Rouen, France, ¹⁵Paris Descartes University, Paris, France, ¹⁶Rheumatology, Brest University Medical School Hospital, Brest, France, ¹⁷Rheumatology, Rheumatology department, Bicetre Hospital, Paris-Sud University, Le Kremlin Bicetre, France, ¹⁸Centre d’Épidémiologie Clinique, AP-HP (Assistance Publique des Hôpitaux de Paris), Hôpital Hôtel Dieu, Paris, France, ¹⁹Department of Rheumatology, Strasbourg University Hospital, Strasbourg, France

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Infection, registry, risk and tocilizumab

Session Information

Date: Tuesday, November 15, 2016

Title: Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy - Poster III

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Observational studies have already reported the risk of serious infections in rheumatoid arthritis (RA) treated with tocilizumab but in limited samples. The aim of this study was to investigate the predictive risk factors of serious infections in the largest European registry of patients treated with tocilizumab for RA.

Methods: 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 P value less than 0.15 were entered into the multivariate model. Multiple imputation was used to compensate missing data in some variables. A P value <0.05 was considered statistically significant.

Results: 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 Haemophilus influenzae infection. Favourable outcome was observed in most cases. Fouropportunistic infections were reported: 1 Pneumocystosis, 1 tuberculosis, 1 Haemophilus influenzae infection and 1infection related to Klebsiella pneumoniae. A pathogen was identified in 41 cases. TCZ was definitively stopped for 35patients. The incidence of serious infection was stable over the first 3 years of follow-up in the registry. Bivariate analysisidentified 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 ofpolymorphonuclear 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.

Conclusion: 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.

Disclosure: J. Morel, None; A. CONSTANTIN, None; G. Baron, None; E. Dernis, None; R. M. Flipo, None; S. Rist Bouillon, None; B. Combe, None; J. E. Gottenberg, None; T. Schaeverbeke, None; M. Soubrier, None; O. Vittecoq, None; M. Dougados, None; A. Saraux, None; X. Mariette, Pfizer, GlaxoSmithKline, and Roche, 2,Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Roche, UCB Pharma and Sanofi-Aventis, 5; P. Ravaud, None; J. Sibilia, None.

To cite this abstract in AMA style:

Morel J, CONSTANTIN A, Baron G, Dernis E, Flipo RM, Rist Bouillon S, Combe B, Gottenberg JE, Schaeverbeke T, Soubrier M, Vittecoq O, Dougados M, Saraux A, Mariette X, Ravaud P, Sibilia J. Risk Factors of Severe Infections in Patients with Rheumatoid Arthritis Treated with Tocilizumab in the French Registry Regate (REGISTRY –ROACTEMRA) [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/risk-factors-of-severe-infections-in-patients-with-rheumatoid-arthritis-treated-with-tocilizumab-in-the-french-registry-regate-registry-roactemra/. Accessed .

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