Clinical significance of tocilizumab-related neutropenia in patients with rheumatoid arthritis

Abstract

Objective: To determine the risks and clinical significance of tocilizumab (TCZ)-related neutropenia, in real-world settings, for patients with rheumatoid arthritis (RA).

Methods: Medical records of RA patients treated with TCZ at a tertiary referral hospital in South Korea were collected. Infectious complications were defined as cases confirmed by clinical diagnosis and treated with antibiotics.

Results: A total of 277 RA patients with TCZ treatment (intravenous: 152 [54.9%], subcutaneous: 125 [45.1%]) were included in our study. During the observational period, 22 (7%) patients experienced grade 3 neutropenia. No patients discontinued TCZ due to neutropenia, while the dosage of conventional synthetic DMARD (csDMARD) was either reduced or discontinued for 8 patients. Patients, who experienced neutropenia while using csDMARD, had a higher risk for grade 3/4 neutropenia during TCZ treatment (hazard ratio [HR]: 3.120, 95% CI: 1.189-8.189, P=0.021). Among infections, pulmonary infections were the most common (10.35 per 100 patient-years). Age over 60 years (HR: 2.133, 95% CI: 1.118-4.071, P=0.022) and the presence of extra-articular manifestations (adjusted HR: 11.096, 95% CI: 5.353-22.999, P<0.001), but not neutropenia (adjusted HR: 1.263, 95% CI: 0.269-5.945, P=0.77), were risk factors for infections during TCZ treatment.

Conclusion: Approximately 7% of RA patients treated with TCZ developed grade 3 neutropenia. The previous history of neutropenia during csDMARD was a risk factor for TCZ-related neutropenia. Age and extra-articular manifestations, but not neutropenia, were risk factors for infection during TCZ treatment, suggesting that TCZ treatment can be maintained in the presence of neutropenia unless infection occurs.