Neutropenia in Patients Treated With TNF-α Inhibitors: Frequency and Clinical Implications From a Retrospective Cohort

Tumor necrosis factor-alpha (TNF-α) inhibitors, including infliximab, etanercept, adalimumab, certolizumab, and golimumab, have become cornerstone therapies in the management of rheumatologic disorders. Although their efficacy and tolerability are well established, accumulating evidence indicates that these agents may also induce hematologic adverse events. The most frequently documented hematologic complication of TNF-α inhibitor therapy is neutropenia. Previous studies have reported neutropenia in approximately 10-19% of patients receiving TNF-α inhibitors.

Neutropenia is defined as a decrease in circulating neutrophils to an absolute neutrophil count (ANC) below 1500 cells/μL. Clinically, neutropenia is stratified according to the ANC as mild (1000-1500/μL), moderate (500-1000/μL), or severe (<500/μL). While mild neutropenia is frequently asymptomatic, severe neutropenia is associated with a substantially elevated risk of serious and potentially life-threatening infections .

The pathophysiological mechanisms underlying drug-induced neutropenia remain incompletely understood; however, proposed explanations include immune-mediated peripheral destruction of granulocytes, bone marrow suppression or impaired maturation of granulocyte precursors. Autoimmune pathways may also contribute, as evidenced by recurrence of neutropenia following drug rechallenge.

Neutropenia associated with TNF-α inhibitor therapy is typically mild; however, its development warrants careful clinical attention. Certain clinical risk factors have been identified. Identified risk factors include a previous history of neutropenia, prior neutropenia under disease-modifying antirheumatic drugs (DMARDs) therapy, and lower baseline neutrophil counts, each of which may predispose patients to subsequent neutropenia. Notably, most cases emerge within the first three months after treatment initiation. Although discontinuation is rarely required and serious infections are uncommon, the possibility of hematologic complications underscores the importance of close monitoring and routine hematologic assessments throughout therapy. Despite the growing recognition of TNF-α inhibitor-induced neutropenia, current data regarding its rate, clinical course, and impact on treatment outcomes remain limited, particularly in real-world patient populations. The present study aimed to determine the frequency of neutropenia in this population and to evaluate its clinical characteristics and impact on treatment outcomes.