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Reslizumab (CINQAIR) is a humanized, anti-IL-5 biologic agent approved by FDA in March 2016 as add-on treatment for asthma with peripheral blood eosinophilia, uncontrolled by usual treatments.
In two randomized trials, reslizumab improved lung function and asthma symptoms in patients meeting these criteria. Patients without high eosinophil count in peripheral blood did not experience clinically meaningful effects on lung function and symptom control.
The two manufacturer-funded phase III studies were published in CHEST.
Eosinophils are important in the initiation and perpetuation of airway inflammation and airway remodeling. Asthma varies widely in its presentation and pathophysiology, but several asthma phenotypes are characterized by high eosinophil counts in the blood, sputum, and airways.
CINQAIR acts by tightly binding the cytokine IL-5, preventing its activation of its receptor; this inhibition prevents activation of eosinophils and subsequent inflammation.
In one of the studies, patients with poorly controlled asthma were randomized to receive intravenous reslizumab 3.0 mg/kg or placebo once every 4 weeks for 16 weeks. Patients were stratified and analyzed by baseline blood eosinophil count (<400 cells/μL or ≥400 cells/μL). The primary outcome was change in FEV1 from baseline to week 16. Secondary endpoints included asthma control scores, use of short-acting beta-agonists (SABAs) and forced vital capacity (FVC).
A total of 492 patients received one or more doses of placebo (n=97) or reslizumab (n=395).
- Overall, mean FEV1 change from baseline to week 16 was not significantly different between reslizumab and placebo-treated patients.
- In the ≥400 cells/μL subgroup, treatment with reslizumab was associated with improvements in lung function, asthma control, and albuterol use.
- Reslizumab had fewer overall adverse events compared with placebo (rate of 55% versus 73%).
The other study enrolled only patients with elevated blood eosinophil counts (≥400 cells/μL), including adults and children age 11 and older with asthma uncontrolled by inhaled corticosteroids at a medium or higher dose.
All patients were randomized to receive reslizumab at 0.3 or 3.0 mg/kg or placebo once every 4 weeks for 16 weeks. The primary endpoint was change from baseline in pre-bronchodilator FEV1 over 16 weeks. Secondary endpoints included other lung function measures, albuterol use, blood eosinophils and self reported asthma control scores.
Reslizumab significantly improved FEV1 at both the lower (+115 mL) and the higher doses (+160 mL). FVC was also increased by 130 mL at the higher dose, and asthma control scores were as well.
Side effects (asthma worsening, headache, and nasopharyngitis) were generally mild to moderate in severity.
Which patients will respond to CINQAIR?
The optimal cut-off point for clinically relevant eosinophil count as an eligibility test for reslizumab remains unclear. An editorialist noted:
From a patient perspective there is an argument to select a low or no cut-off as there is some benefit even with low baseline eosinophil counts, whereas from a payer's perspective the health economic benefit is better with a higher cut-off ... post-licensing research will be needed to address the effectiveness of these therapies in real world studies.
One healthcare insurer published online its criteria used to determine patient eligibility for payment for CINQAIR:
- 18 years of age or older; and
- Eosinophilic phenotype as determined by blood eosinophils of 400 cells/μL or higher prior to initiation of therapy (within 4 weeks of dosing) ; and
- History of severe asthma attacks (1 or more exacerbations in the previous year) despite regular use of high-dose inhaled corticosteroids (ICS) with oral corticosteroids (CS) for at least 6 months or high-dose ICS without oral CS for at least 12 months.
Reslizumab for Inadequately Controlled Asthma With Elevated Blood Eosinophil Levels: A Randomized Phase 3 Study. Chest. 2016 Oct;150(4):789-798.
Phase 3 Study of Reslizumab in Patients With Poorly Controlled Asthma: Effects Across a Broad Range of Eosinophil Counts. Chest. 2016 Oct;150(4):799-810.