Safety of Reslizumab in Uncontrolled Asthma with Eosinophilia: A Pooled Analysis from 6 Trials.

BACKGROUND: Intravenous reslizumab, a monoclonal IL-5 antibody, is approved for treating severe asthma with eosinophilia. Limited structured information is available on the safety of reslizumab in larger populations. OBJECTIVE: To investigate the safety profile of intravenous reslizumab 3.0 mg/kg by analyzing data from 6 asthma clinical trials: 5 placebo-controlled (duration ≤52 weeks) and 1 open-label extension (up to 2 years of treatment). METHODS: Patients were aged 12 to 75 years with inadequately controlled asthma with eosinophilia. In the placebo-controlled trials, 730 patients received placebo and 1028 received reslizumab 3.0 mg/kg. RESULTS: Adverse events (AEs) and serious AEs occurred in higher percentages of patients in the placebo group (81% and 9%) than in the reslizumab group (67% and 6%). Asthma, nasopharyngitis, and upper respiratory tract infection were the most common AEs with placebo and reslizumab. Three cases of anaphylaxis, related to reslizumab, were successfully managed with standard therapies. No significant difference in the incidence of malignancies was seen when compared with placebo or the general population. Among 756 patients with more than 12 months of reslizumab exposure, the AE rate was lower than in the placebo-controlled trials (367.3 vs 433.9 events/100 patient-years). The incidence of AEs in patients on treatment for more than 12 months was no higher than in patients with shorter treatment durations. CONCLUSIONS: This analysis confirms that treatment with intravenous reslizumab for more than 12 months is well tolerated in patients with asthma, with no evidence of rare safety events that were not detected in individual trials.

Long-term Safety and Efficacy of Reslizumab in Patients with Eosinophilic Asthma.

BACKGROUND: In placebo-controlled trials, reslizumab, an anti-IL-5 monoclonal antibody, significantly reduced asthma exacerbations and improved lung function and asthma control in patients with eosinophilic asthma. OBJECTIVE: This open-label extension study evaluated safety and efficacy of reslizumab for up to 24 months. METHODS: After participation in 1 of 3 placebo-controlled, phase III trials in moderate-to-severe eosinophilic asthma, patients received reslizumab 3.0 mg/kg intravenously every 4 weeks for up to 24 months. Adverse events (AEs), lung function, and patient-reported asthma control were evaluated. RESULTS: In the open-label extension, 1,051 patients received ≥1 reslizumab dose (480 reslizumab-naïve, 571 reslizumab-experienced); median (range) exposure was 319 (36-840) and 343 (36-863) days in reslizumab-naïve and reslizumab-experienced patients, respectively. Continuous exposure, including during the placebo-controlled studies, was ≥12 months for 740 patients and ≥24 months for 249 patients. The most common AEs were worsening of asthma and nasopharyngitis. Serious AEs affected 78 of 1,051 (7%) patients; 18 of 1,051 (2%) discontinued treatment because of AEs; and there were 3 deaths (all non-treatment-related). Fifteen adult patients (15 of 1,023; 1%) had malignancies of diverse tissue types. Reslizumab-experienced patients maintained improved lung function and asthma control; reslizumab-naïve patients had improvements in these measures throughout open-label treatment. Blood eosinophil counts appeared to be returning to baseline after reslizumab discontinuation. CONCLUSIONS: In patients with moderate-to-severe eosinophilic asthma, intravenous reslizumab 3.0 mg/kg displays favorable long-term safety and sustained long-term efficacy. Initial improvements in lung function and asthma control were maintained for up to 2 years. These findings substantially add to our understanding of the long-term safety and efficacy of anti-IL-5 strategies.