Background/Purpose

With the expanding use of Biological Agents (BA), in particular TNF inhibitors, opportunistic infections (OI) are a major concern in Rheumatology. Our purposes were to describe the incidence of OI global and by periods in Rheumatoid Arthritis (RA), and comparing the risk of OI by BA.

Methods

We performed a retrospective longitudinal observational study from 2000 to 2013. We included subjects followed in our outpatient clinic, diagnosed with RA according to ACR criteria 87, whom started treatment with a BA [etanercept (ETN), golimumab (GOLI), certolizumab (CTZ), infliximab (IFX), adalimumab (ADA), rituximab (RTX), abatacept (ABA), or tocilizumab (TCZ)].  Our primary endpoint was OI that involved the suspension of the BA. We consider OI when there was a positive culture (for Virus, Fungus, and bacterial) or compatible symptoms that responded to specific treatment. We also collected secondary variables: sociodemographic (age, sex); clinical (disease duration, type of BA, hospital admission, previous BA). We used survival techniques to estimate the incidence of OI, expressed per 1000 patient-year [CI 95 %]. The exposure time was defined from the start date of each BA to its suspension, loss of follow up or end of study (23/11/2013). We performed Cox regression models (adjusted by age, duration of RA, sex, calendar time and prior BA) to compare the risk of OI between each BA.

Results

453 RA patients were included in the study; they started 853 different courses of BA treatment. Of these, 81% were women with a mean age at diagnosis of 52.4 ± 14 years. The median time from onset of BA until onset of OI was 1.7 years [0.48-2.8]. Except for one all patients with OI took steroids. The most frequently used drug was ADA (33%), followed by ETN (25%), IFX (19%) and RTX (14%). There were 33 OI [22 Virus (18 Herpes Zoster, 2 virus B reactivation, 1 Avian flu), 10 Fungus (Candida, 2 Aspergillus), and 1 Bacterian (Legionella)], 36% required hospitalization and 4 died (2 fungus infection, 1 Legionella and 1 virus B reactivation with a myelodisplasic syndrome). The global incidence of OI was 17.7 [12.5-24.8]. TZC had 1 OI, with a incidence of 68.1 [9,6-483,5], followed by RTX, with 4 OI, Incidence 22.2 [8.3 to 59];  ADA, with 14 OI, Incidence : 19.9 [11,8-33,6];  IFX with 9 OI, Incidence: 19.4 [10,1-37,3], and ETN with 5 OI, Incidence: 11.6 [4,8-27,9].  We not find statistical differences in the rate of OI between BA. Age was found a predictor of OI in the multivariate analysis.

Conclusion

The incidence of OI and its evolution over time in real life conditions is described. Incidence found was near 18 cases per 1000 patients -year.  Four of them resulted in death. Incidence of opportunistic infections showed no variance during the years. We did not find statistical differences in the rate of OI between BA. Doctors using Biological Agents should be concerned about this problem and be aware for the detection and management of OI.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/incidence-of-opportunistic-infections-in-rheumatoid-arthritis-treated-with-biological-agents/