AB0425 Prevalence and risk factors of serious infections in rheumatoid arthritis patients receiving the biologic/targeted synthetic dmards: a propensity score analysis from the hong kong biologics registry
Authors: C.C. Mok, R. Wan, B. Fong
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To study the prevalence and risk factors for serious infections in rheumatoid arthritis (RA) patients receiving the biologic/target synthetic (b/ts)DMARDs. <h3>Methods</h3> Patients who fulfilled the EULAR/ACR criteria for RA and were ever treated with b/tsDMARDs were included. Withdrawal of b/tsDMARDs due to serious adverse events (SAEs) and serious infections (SIs) was analysed. Demographic data, medical comorbidities and concomitant use of glucocorticoids and csDMARDs were retrieved and their contribution to SIs was evaluated by logistic regression. The propensity score for SIs was calculated and patients were stratified into 5 quintiles. The hazard ratios (HRs) of SIs with respect to individual b/tsDMARDs in each quintile were studied by Cox regression. <h3>Results</h3> Up to December 2017, 2355 courses of b/tsDMARDs were used in 1355 RA patients (83% women; age 54.0±12.7 years). The usage of various b/tsDMARDs was: adalimumab(12%), etanercept(24%), infliximab(17%), golimumab(9.4%), certolizumab(0.9%), tocilizumab(19%), rituximab(6.6%), abatacept(7.7%) and tofacitinib(2.7%). After a follow-up of 5056 patient-years, 1433 courses of b/tsDMARDs were discontinued, with major reasons being inefficacy (50%), SAEs (22.4%) and cost (8.4%). Among those b/tsDMARD courses terminated because of SAEs, 32% were due to SIs (103 episodes). The rate of SIs was 1.17/100 patient-years. The commonest causes of SIs were pulmonary tuberculosis (TB) (41%), severe pneumonia (33%), soft tissue infection (6.8%), atypical TB (2.9%), urogenital sepsis (2.9%), septic arthritis (2.9%), hepatobiliary/gastrointestinal sepsis (2.9%), central nervous infection (1%), severe viral infections including herpes zoster (5.8%), and opportunistic infections (2.9%). A logistic regression model showed that increasing age (OR1.02 [1.001–1.04 per year]), male sex (OR1.88 [1.08–3.26]) and concomitant chronic obstructive pulmonary disease/asthma (OR2.55 [1.05–6.23]) were risk factors significantly associated with SIs. The rate of TB infection was highest in users of infliximab (2.32/100 patient-years), followed by tofactinib (1.47), adalimumab (1.27), etanercept (0.62) and tocilizumab (0.36). Non-TB SIs occurred most frequently with infliximab (2.32/100 patient-years), tofacitinib (1.47) and abatacept (1.15). In the quintile of patients with the highest propensity score for SIs, infliximab had the highest withdrawal rate due to SIs (18%), followed by tofacitinib (10%), etanercept (8%), adalimumab (6%), abatacept (2.8%) and tocilizumab (2.6%). Cox regression revealed the following HRs for SIs with reference to adalimumab: infliximab (2.81 [0.80–9.88]), tofacitinib (HR 2.12 [0.19–23.4]), etanercept (HR 0.82 [0.22–3.11]), abatacept (HR 0.41 [0.04–3.98]) and tocilizumab (HR 0.38 [0.06–2.26]). Concomitant low-dose glucocorticoid was associated with an insignificantly increased risk of SIs only in the three quintiles of patients with lower propensity to SIs. <h3>Conclusions</h3> SIs causing withdrawal of b/tsDMARDs in patients with RA account for one-third of all SAEs. Increasing age, male sex and concomitant chronic chest conditions were independent risk factors for SIs. Infliximab was associated with the highest rates of serious TB and non-TB infection, and this observation was consistent in all quintiles of patients with different propensity to SIs. <h3>Disclosure of Interest</h3> None declared