A review of safety data and profiles of anti-interleukin-5 (IL-5) biologics used in eosinophilic asthma showed a potential rise in incomplete therapeutic effects, a finding that could adversely affect the benefit-risk profile of these drugs. This was among the findings of a systematic review and meta-analysis published in BMC Pulmonary Medicine.
Investigators conducted a systematic review and meta-analysis that evaluated the overall safety profile of anti-IL-5 treatments (mepolizumab, benralizumab, and reslizumab) and sought to identify potential novel safety signals.
A search was performed in the PubMed, EMBASE, Web of Science, and Cochrane Library databases for relevant articles published from the earliest available date through September 2022. Eligible studies were randomized, placebo-controlled trials in patients with eosinophilic asthma.
Postmarketing adverse event data for mepolizumab, benralizumab, and reslizumab were obtained from the FDA Adverse Event Reporting System (FAERS) from January 1, 2018, to September 30, 2022. The top 100 adverse events (AEs) at a preferred term level by number of cases were identified through signal detection.
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An incomplete therapeutic effect surfaced as a new suspect signal for all anti-IL-5 drugs.
The analysis included 24 randomized, placebo-controlled trials with 10,201 patients diagnosed with eosinophilic asthma (6238 female). Participants’ ages ranged from 6 to 82 years. Of the 10,171 patients who were treated, 6260 received anti-IL-5 therapy, and 3911 received a placebo.
Overall AEs were documented in 22 studies from 20 published articles: 68.93% (3765/5462) of patients who received anti-IL-5 therapy had AEs vs 71.84% (3791/5277) in those who received placebo. In the anti-IL-5 group, the incidence of general AEs was similar compared with the placebo group (risk ratio [RR],0.97; 95% CI, 0.93-1.00; P =.000, I2 =54.0%).
A total of 23 studies reported serious AEs (SAEs) in 21 published articles: 8.22% (495/6025) of patients who received anti-IL-5 drugs had an SAE vs 11.20% (657/5867) who received placebo. The overall SAE incidence in the anti-IL-5 group was significantly lower compared with the placebo group (RR, 0.76; 95% CI, 0.68-0.85; P =.526, I2 =0.0%), which exclusively occurred in patients who received mepolizumab (RR, 0.66; 95% CI, 0.54-0.82; P =.399; I2 =4.7%) and benralizumab (RR, 0.77; 95% CI, 0.67-0.89; P =.567; I2 =0.0%).
Nasopharyngitis, asthma worsening, headache, upper respiratory tract infection, and bronchitis were the 5 most frequently occurring AEs reported among patients who used anti-IL-5 drugs.
A total of 10,589,313 AEs were reported in FAERS from January 1, 2018, to September 30, 2022, of which 28,478 implicated mepolizumab, benralizumab, and reslizumab.
Overall, of the top 100 AEs associated with anti-IL-5 drugs, 75 suspicious observations were observed involving 16 system organ classes. The comprehensive safety profile for anti-IL-5 drugs from these suspect observations was primarily regarded as manifestations associated with disease progression, uncontrolled underlying conditions, and incomplete therapeutic effect, including clinical signs, symptoms, reduced quality of life, and anomalous lab results. The safety characteristics of anti-IL-5 drugs based on signal detection showed general similarity with mepolizumab and benralizumab’s signal detection findings. Results for reslizumab did not indicate events related to infections, product issues, and inappropriate usage.
Of the top 100 AEs associated with mepolizumab, benralizumab, and reslizumab, 78 suspect observations were found for mepolizumab, 66 for benralizumab, and 24 for reslizumab.
Limitations include the availability of only a fraction of AEs being published and the small number of studies included. Also, quantitative analysis was part of the process to identify suspect observations.
“The comprehensive safety profile of anti-IL-5 drugs predominantly embodied manifestations associated with disease progression and incomplete therapeutic effect,” the researchers stated. “AEs including infections, hypersensitivity, headache, pyrexia, and injection/infusion site reactions were related to product pharmacological properties and the mode of action, while incorrect dose administration and product exposure were tied to inappropriate usage and product issue.”
