AB0451 Incidence of opportunistic infections during rituximab, abatacept or tocilizumab treatments for rheumatoid arthritis in clinical practice
Authors: L. Leon, M. Peñuelas, F.J. Candel, D. Freites, L. Rodriguez, J.A. Jover, L. Abasolo
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> With the expanding use of biologic disease-modifying anti-rheumatic drugs (bDMARDs), opportunistic infections (OI) are a major concern in Rheumatology. <h3>Objectives</h3> Our purposes were to describe and compare the incidence of OI in RA treated by non-TNF-targeted biologics. <h3>Methods</h3> We performed a retrospective longitudinal observational study from 2007 to 2017. We included subjects followed in our outpatient clinic, diagnosed with RA according to ACR criteria, whom started treatment with a bDMARD [rituximab (RTX), abatacept (ABA), or tocilizumab (TCZ)]. According to the microbiologist criteria, we consider OI when there was a positive culture (for Virus, Fungus, bacterial or parasitary) or compatible symptoms that responded to specific treatment. Severe IO was considered if required hospitalisation. We also collected secondary variables: sociodemographic, clinical and other treatments. We used survival techniques to estimate the incidence of OI, expressed per 1000 patient-year [CI 95%]. Exposure time was defined from the start date of each bDMARDs until the development of an OI, discontinuation, loss of follow up or end of study (01/02/2017). <h3>Results</h3> We analysed a total of 164 patients with 219 different courses of bDMARDs treatment. Of these, 76% were women with a mean age at first bDMARD of 61.4±15 years. Rheumatoid factor was positive in 73.6%. Main comorbidities were: Hypercholesterolemia (53.3%), Hypertension (53.2%), Depression (25%), Diabetes (15%), and Ischaemic Heart Disease (9.8%). VSG mean was 38±28, and the mean WBC count was 7.8±2.7. The median time from onset of RA until onset of bDMARD was 2.8 years [0.8–6.2]. Of these, 132 were on RTX, 47 were on ABA and 40 were on TCZ. There were 12 OI (9 with RTX, 2 with ABA and 1 with TCZ). RTX have 2 Fungus (Candida krusei and Klebsiella), and 7 Virus (4 Herpes Zoster, 1 virus B reactivation, 1 virus C reactivation). OI for ABA was 2 Virus (1 Herpes Zoster, 1 virus B reactivation), while we found one virus OI with TCZ Fungus (Herpes Zoster). There were no bacterial or parasitary OI. Global incidence rate of OI was 30.49 [17.3–53.6]. The incidence of OI was 38.92 [20.2–74.8] for RTX, followed by ABA with 21.61 [5.4–86.4], and TZC with 14.3 [2–101.6]. We found 3 severe OI (2 fungus infections, 1 virus B reactivation). The incidence of severe OI was 7.62 [2.4–23.6], all of them requiring hospitalisation with no deaths. Severe OI have a higher incidence for men 21.1 [5.2–84.2] than women 3.3 [0.4–23.7]. All patients with severe OI were taking corticosteroids, and at least one synthetic DMARD. TCZ did not have any severe OI, and the incidence of severe OI was 10.8 [1.5–76.7] for ABA, followed by RTX with 8.6 [2.1–34.5]. <h3>Conclusions</h3> The incidence of OI in three non-TNF-targeted biologics in real life conditions is described. Incidence found was near 31 cases per 1000 patients -year. Virus and fungus are the OI more frequents in these bDMARDs. Doctors using bDMARDs should be concerned about this problem and be aware for the detection and management of OI. <h3>Disclosure of Interest</h3> None declared