Neutropenia in patients receiving anti–tumor necrosis factor therapy

Abstract

Objective. To examine the rates of and risk factors for neutropenia together with the dynamics of neutrophil and other white cell subset counts in a cohort of patients treated with a tumor necrosis factor (TNF) inhibitor for inflammatory arthritis. Methods. We performed a retrospective cohort study examining the association between baseline demographics, clinical features, medications used, and development of neutropenia, and behavior of neutrophil and other white cell subset counts during TNF inhibitor therapy. Results. In 367 patients (298 [81.2%] with rheumatoid arthritis, 38 [10.4%] with ankylosing spondylitis, and 31 [8.4%] with psoriatic arthritis), 69 (18.8%) had at least one episode of neutropenia (<2.0 ؋ 10 9 /liter) during TNF inhibitor therapy, and of these, 6% developed serious infections secondary to neutropenia. There was no significant difference in disease, demographic, or drug variables between patients with and without neutropenia. However, patients with neutropenia had significantly lower baseline neutrophil counts (4.2 ؋ 10 9 /liter; 95% confidence interval [95% CI] 3.8, 4.6 versus 6.2 ؋ 10 9 /liter; 95% CI 6.0, 6.5), and a previous history of neutropenia while receiving disease-modifying antirheumatic drugs increased the risk while receiving TNF inhibitors (hazard ratio 2.97; 95% CI 1.69, 5.25). A significant drop in mean neutrophil count (1.12 ؋ 10 9 /liter; 95% CI 0.92, 1.32) was observed after 2 weeks of TNF inhibitor therapy. Other white cell subsets tended to significantly increase. Conclusion. TNF inhibitor therapy is associated with a significant reduction in peripheral blood neutrophil count, leading to 19% of patients becoming neutropenic. Risk of neutropenia is significantly higher in patients with a low baseline neutrophil count or previous history of neutropenia. We suggest that patients receiving TNF inhibitor therapy would benefit from regular complete blood cell count monitoring.

Association between TNF-α-308G>A and -238G>A gene polymorphisms and TNF-α serum levels in Mexican colorectal cancer patients

“…However, TNF-α upregulates the expression of proinflammatory cytokines involved in the differentiation and maturation of hematopoietic stem cells, and it is possible that TNF-α blockade mediates bone marrow failure by inhibiting stem cell differentiation. TNF-α has been shown to directly exert a complex and dual effect on neutrophils, accelerating apoptosis in some cells, yet prolonging the survival of others (Hastings et al, 2010).…”

Should anti-TNF therapy be discontinued in rheumatoid arthritis patients undergoing elective orthopaedic surgery? A systematic review of the evidence

“…Anti-TNF is associated with development of neutropenia shortly after initiation of treatment [46][47][48]. Furthermore, previous studies have shown that RA patients are at an inherently increased risk of infection as a consequence of their disease [13][14][15][16][17][18][19][20][21].…”

Differential Adverse Events Between TNF-α Inhibitors and IL-17 Axis Inhibitors for the Treatment of Spondyloarthritis

“…This was noted to be transient and resolved with continued therapy [24]. Cytopenias have been reported in TNF-inhibitor trials, including thrombocytopenia, lymphocytopenia, and neutropenia [25,26]. These cytopenias are generally mild and transient.…”