Background/Purpose:

Biologic disease-modifying anti-rheumatic drugs (bDMARDs) may be associated with opportunistic infections. Our purposes were to describe their incidence in Rheumatoid Arthritis (RA) taking bDMARDs, and compare the risk of development between TNF-targeted and non-TNF-targeted biologics.

Methods:

Retrospective longitudinal study from 2007 to 2017. We included RA patients, from our outpatient clinic, whom started treatment with a TNF-targeted bDMARD [etanercept (ETN), golimumab (GOLI), certolizumab (CTZ) , infliximab (IFX), adalimumab (ADA)], or non-TNF-targeted bDMARD [rituximab (RTX), abatacept (ABA), or tocilizumab (TCZ)]. We consider OI according to microbiologist criteria [An “indicator opportunistic infection after biological (IOIb)” according to consensus recommendations of the presence, or specific presentation, of a pathogen that suggests a greater probability of an alteration in the immunity in a host under treatment with bDMARDs¹]. Independent variable was the type of targeted bDMARD: TNF vs non-TNF. Secondary variables: sociodemographic; clinical and treatments. We used survival techniques to estimate the incidence of IOIb, per 1000 patient-year [CI 95 %]. The exposure time was defined from the start date of each bDMARD to the development of an IOIb, loss of follow up or end of study. We performed a Cox multivariate regression model to compare the risk of IOIb. Results were expressed in Hazard ratio (HR).

Results:

441 RA patients were included, starting 761 different courses of bDMARDs. 81% were women with a mean age at first bDMARD of 57.3±14 years. 71.3% of the courses were TNF-targeted bDMARDs and 28.7% non-TNF-targeted bDMARDs. There were 38 OI [26 Viral infections (18 Herpes Zoster, 2 VHB reactivation, 3 VHC reactivation, 1 Epstein Bar virus, 1 H1N1 flu, 1 CMV reactivation), 6 Fungal infections (5 Invasive-oropharyngeal candidiasis, 1 dermatophytosis by Trichophyton spp), 5 Bacterial infections (1 Legionellosis, 1 Salmonellosis and 3 Tuberculosis), 1 parasitic (Leishmaniasis)]. 9 of them required hospitalization and one died. The median time from onset of bDMARD until IOIb was 3.1 years [0.5-4.6]. The global incidence of IOIb was 21.8 [15.9-30]. TNF-targeted bDMARDs had 26 IOIb, incidence 19.8 [13.4-29.1], and non-TNF-targeted bDMARDs had 12 IOIb, incidence 28.1 [16-49.6]. In the multivariate analysis (adjusted by age, sex and calendar-time), we did not find statistical difference between type of targeted bDMARDs (HR 1.37, p=0.4), whereas male sex achieved a significant risk for IOIb (HR 2.18, p=0.04). Age (HR 1.02, p=0.08), concomitant treatment with glucocorticosteroids (HR 6.67, p=0.05) and leukopenia (HR 2.73, p=0.08) showed a tendency to increase the risk of IOIb.

Conclusion:

Incidence of IOIb due to bDMARDs was near 22 cases per 1000 patients–year. Crude incidence was higher for non-TNF-targeted bDMARDs compared to TNF-targeted bDMARD, moreover this difference was not maintained in the multivariate analysis. Close monitoring should be taken in those RA patients treated with bDMARDs and glucocorticoids, and those with leukopenia, mainly elderly and male patients.

1. Winthrop et al. Ann Rheum Dis 2015; 74: 2107-2116

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/indicator-opportunistic-infections-after-biological-treatment-in-rheumatoid-arthritis-10-years-follow-up-in-clinical-practice/