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

ObjectiveTo determine the risks and clinical significance of tocilizumab (TCZ)-related neutropenia, in real-world settings, for patients with rheumatoid arthritis (RA).MethodsMedical 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.ResultsA 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.ConclusionApproximately 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.