Incidence of serious respiratory infections in patients with rheumatoid arthritis treated with tocilizumab

Abstract

We aimed to demonstrate the incidence of serious respiratory infections in patients with rheumatoid arthritis (RA) treated with tocilizumab (TCZ) monotherapy. We analyzed the incidence of serious respiratory infections in 601 RA patients enrolled in TCZ clinical trials and their extension studies (TCZ cohort) and in 601 age- and sex-standardized RA patients treated in daily clinical practice at Tokyo Women's Medical University (IORRA subsample cohort). The rates of serious respiratory infections were 1.77 per 100 patient-years from 1999 to 2008 in the TCZ cohort and 0.53 per 100 patient-years from 2000 to 2009 in the IORRA subsample cohort. With the IORRA subsample cohort regarded as a standard population, the standardized incidence ratio (SIR) of serious respiratory infection in the TCZ cohort was 3.64 [95% confidence interval (CI) 2.56-5.01], standardized for age and sex; 2.35 (95% CI 1.66-3.24), standardized for age sex, and corticosteroid use; 1.85 (95% CI 1.30-2.55), standardized for age sex, and pre-existing pulmonary involvement; and 2.41 (95% CI 1.68-3.34) standardized for age sex, and disease activity. The risk of serious respiratory infection in the TCZ cohort was approximately double that in the IORRA subsample cohort after standardizing for corticosteroid use, pre-existing pulmonary involvement, or disease activity. This is comparable to the risk reported when tumor necrosis factor (TNF) inhibitors are used.

Fatal Complication of <i>Legionella pneumophila</i> Pneumonia in a Tocilizumab-treated Rheumatoid Arthritis Patient

“…TCZ is another available biologic for RA, exerting its effects by blocking IL-6 signaling and thus inhibiting the inflammatory pathway, resulting in reduced fever and reduced production of acute phase reactants such as CRP (6). According to data from clinical trials and post-marketing surveillance, RA patients on TCZ therapy have a higher risk of infections, especially lower respiratory tract infections (8)(9)(10). Previously, severe bacterial pneumonia cases were reported in RA patients receiving TCZ therapy (19).…”

“…It has been reported that the use of biologics increases the incidence of infection, particularly lower respiratory tract infections (7). The use of TCZ also significantly increases the risk of serious respiratory infections (8,9), the standardized incidence rate of which was reported to be 3.64 with a 95% confidence interval of 2.56-5.01 per 100 patientyears (10).…”

Biological agents and respiratory infections: Causative mechanisms and practice management

“…The central role of this cytokine has been confirmed by successful therapeutic blockade of the IL-6 receptor tocilizumab (TCZ) in patients with RA. In a meta-analysis of clinical trials, TCZ was not associated with a higher risk of serious infection than was the placebo [72], but a Japanese publication suggested that the drug may be associated with an increased risk of respiratory infection [73].…”

Invasive fungal infections in paediatric patients treated with macromolecular immunomodulators other than tumour necrosis alpha inhibitors

“…Tocilizumab (Actemra ® , RoActemra ® ; humanised IgG1 anti‐IL‐6 receptor monoclonal antibody) is indicated for juvenile idiopathic arthritis and has a black box warning for IFIs, while cumulative safety data of 4009 patients have demonstrated 11 cases (0.3%) of IFIs . Regarding the incidence of respiratory fungal infections, tocilizumab monotherapy does not seem to differ from other DMARDs users . Other anti‐IL‐6 agents include siltuximab (Sylvant ® ; used in multicentric Castleman's disease), sirukumab (CNTO 136; used in RA and lupus nephritis) and sarilumab (used in RA), but no records on fungal infections exist.…”