medwireNews: High neutrophil counts, leflunomide treatment, and the absence of anti-citrullinated protein antibodies (ACPAs) are associated with increased risk for serious infection among patients with rheumatoid arthritis (RA) who are treated with tocilizumab, researchers report.
Although biologic agents such as tocilizumab have “considerably improved” prognosis for patients with RA over the past 2 decades, these drugs have “some side effects, in particular serious infections, which need to be considered in the risk–benefit balance,” say Jacques Morel (University of Montpellier, France) and study co-authors.
The team analyzed data from 1491 patients included in REGistry–RoAcTEmra (REGATE), a French registry study investigating the long-term safety and efficacy of tocilizumab, and found that 122 participants treated with the interleukin (IL)-6 inhibitor experienced 125 serious infections requiring hospitalization and/or intravenous antibiotics over a mean follow-up of 27.6 months.
The most common serious infections occurred in the lung and respiratory tract (28%), followed by the skin and soft tissue (26%), with most of the remainder being urogenital, gastrointestinal tract, or articular infections.
Patients with neutrophil counts above 5.0 x109/L at baseline were almost twice as likely to experience a serious infection as those with lower neutrophil counts, with a significant hazard ratio (HR) of 1.94 after imputation of missing data and adjustment for age and disease duration.
Patients receiving concomitant leflunomide treatment had approximately double the risk for serious infection compared with those receiving no disease-modifying antirheumatic drugs (DMARDs) alongside tocilizumab (adjusted HR=2.18), and ACPA-positive individuals were significantly less likely to experience serious infection than those without ACPA antibodies (adjusted HR=0.56).
These findings “confirmed that [leflunomide] co-medication with [tocilizumab] should require more attention for safety, especially in patients with a higher risk of infection,” write the study authors in Rheumatology.
They note that “[t]his is the first time that a high neutrophils level before initiation of [tocilizumab] has been identified as a risk factor for serious infection,” with previous studies showing the opposite association, and suggest that high neutrophil counts may reflect disease activity.
“RA patients with high disease activity may require intensification of their therapies, which may consequently enhance the risk of developing infections,” they hypothesize.
Although their findings identify possible predictive factors of serious infection, Morel et al concede that the study has a number of limitations, “especially the absence of a control group treated with synthetic DMARDs to estimate the risk of serious infections imputed to [tocilizumab] itself.”
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