Background/Purpose:

To study the prevalence and risk factors for serious infections (SIs) in rheumatoid arthritis (RA) patients receiving the biologic / target synthetic (b/ts) DMARDs.

Methods:

Patients with RA included in the Hong Kong Biologics Registry since 2007 ever treated with b/tsDMARDs were studied. Data on withdrawal of b/tsDMARDs due to serious adverse events (SAEs) and SIs was analyzed. Demographic data, medical comorbidities (eg. diabetes mellitus, chronic lung, kidney and liver diseases) and concomitant use of glucocorticoids (GCs) and csDMARDs were retrieved and their contribution to SIs was evaluated by separate logistic regression. The propensity score for SIs was computed and patients were stratified into 5 quintiles according to the risk. The hazard ratios (HRs) of SIs with respect to individual b/tsDMARDs in each quintile were studied by Cox regression.

Results:

2355 courses of b/tsDMARDs were used in 1355 Chinese patients with RA (83% women; mean 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 for 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%). Logistic regression showed that age (OR 1.02[1.001-1.04 per year]), male sex (OR 1.88[1.08-3.26]) and concomitant chronic obstructive pulmonary disease / asthma (OR 2.55[1.05-6.23]) were independent risk factors for SIs. TB infection was most frequent 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 serious infections 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%). Cox regression revealed a highest HR for SIs in infliximab users with reference to adalimumab (2.81[0.80-9.88]), followed by tofacitinib (HR 2.12[0.19-23.4]). Concomitant GC was associated with an insignificantly increased risk of SIs.

Conclusion: 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.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/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/