For a study published in The Journal of Allergy and Clinical Immunology: In Practice, Marc E. Rothenberg, MD, PhD, and colleagues assessed the effectiveness of mepolizumab using baseline BEC and serum IL-5 levels in patients with HES. “This study follows up on data from the primary clinical trial, which demonstrated that mepolizumab is an effective drug for HES, as assessed by decreasing number of disease flares,” Dr. Rothenberg says. “We had previously shown in an earlier phase 3 trial that mepolizumab is a steroid-sparing drug for HES. Based on these datasets, mepolizumab was recently approved for the treatment of HES in patients aged 12 and older.”
Baseline Eosinophils Did Not Predict Mepolizumab Responsiveness
One of the objectives of the study team was to determine if the level of eosinophils in the blood predicts the response to mepolizumab, Dr. Rothenberg notes. “With this in mind, we conducted a post hoc analysis of the data [from the phase III study],” he says. “We found that baseline levels of eosinophils did not predict responsiveness to mepolizumab.”
The post hoc analysis utilized data from the phase III study assessing mepolizumab in patients with HES. Patients aged 12 and older with BEC of at least 1,000 cells/μL at screening, HES for 6 or more months, and two or more flares in the previous year were randomized (1:1) to baseline HES therapy plus 4-weekly subcutaneous administration of mepolizumab or placebo for 32 weeks.
The proportion of patients with change from baseline in Brief Fatigue Inventory (BFI) item 3, experiencing one or more flares, and annualized flare rate, were analyzed by baseline BEC (<1500/≥1500 to <2500/≥2500 cells/μL). Baseline serum IL-5 (<7.81/≥7.81 pg/mL) were used to assess flare outcomes.
Mepolizumab Effective Independently of Pre-Treatment Serum IL-5
In patients experiencing one or more flares, mepolizumab reduced the proportion by 63% to 90% and flare rate by 58% to 84%, according to the study authors. Patients also experienced improved BFI item 3 scores with mepolizumab versus placebo. Undetectable baseline serum IL-5 levels were detected in most patients, and among them, mepolizumab versus placebo decreased the proportion of patients with one or more flares (77%) and flare rate (67%).
Additionally, Dr. Rothenberg and colleagues sought to determine if the baseline level of IL-5, the target of mepolizumab, affected the responsiveness to the drug. “Although we found that most patients had undetectable levels of IL-5 in the sera, even those patients responded to the drug,” Dr. Rothenberg says. “As such, mepolizumab was effective independently of the serum IL-5 before treatment. Taken together, these finding indicate that mepolizumab is a drug that works in a broad spectrum of patients with HES as defined by blood levels of eosinophils and IL-5.”