Biologic treatment eligibility for real-world patients with severe asthma: The IDEAL study

<p><i>Objectives</i>: Severe asthma comprises several distinct phenotypes. Consequently, patients with severe asthma can be eligible for more than one biologic treatment targeting Th2 inflammation, such as anti-interleukin (IL)-5 and anti-immunoglobulin (Ig) E. The objective of this study was to describe treatment eligibility and overlap in treatment eligibility for mepolizumab (anti-IL-5), omalizumab (anti-IgE) and reslizumab (anti-IL-5) in patients with severe asthma, who were recruited from clinical practice. <i>Methods</i>: This cross-sectional, single-visit, observational study in six countries enrolled patients with severe asthma (defined by American Thoracic Society/European Respiratory Society guidelines). Assessable patients were analysed as a total cohort and a sub-cohort, who were not currently receiving omalizumab. Treatment eligibility was defined according to the local prescribing information or protocol-defined inclusion/exclusion criteria. Patients currently receiving omalizumab were automatically categorised as omalizumab-eligible. <i>Results</i>: The total cohort comprised 670 patients who met the analysis criteria, of whom 20% were eligible for mepolizumab, 31–41% were eligible for omalizumab (depending on eligibility criteria used), and 5% were eligible for reslizumab. In patients not currently receiving omalizumab (<i>n</i> = 502), proportions eligible for each biologic were similar (mepolizumab: 20%, reslizumab 6%) or lower (omalizumab 7–21%) than those for the total cohort. Overlap in treatment eligibility varied; in mepolizumab-eligible patients not currently receiving omalizumab (<i>n</i> = 101), 27–37% were omalizumab-eligible and 18% were reslizumab-eligible. <i>Conclusions</i>: Treatment eligibility for mepolizumab and omalizumab was higher than that for reslizumab. Although there was some overlap in treatment eligibility, the patient groups eligible for treatment with anti-IL-5 or anti-IgE therapies were often distinct, emphasising the different phenotypes and endotypes in severe asthma.</p

Breathing pattern and operating lung volume measurements versus work rate during incremental treadmill exercise.

<p>(A) Breathing frequency (<i>F</i>b), (B) tidal volume, (C) inspiratory capacity (IC), and (D) inspiratory reserve volume (IRV) showing that all three groups reach a similar minimal value at end-exercise (shaded area). Data are shown as mean ± standard error. TLC, total lung capacity. *p<0.05 GOLD 1 and 2 versus controls at a standardized work rate; ^#p<0.05 GOLD 1 versus controls; ^†p<0.05 GOLD 2 versus GOLD 1 and controls (confidence intervals do not overlap indicating p<0.05).</p

Pulmonary function.

<p>Data are presented as mean ± standard deviation.</p><p>GOLD, Global Initiative for Chronic Obstructive Lung Disease; FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; SVC, slow vital capacity; IC, inspiratory capacity; FRC, functional residual capacity; RV, residual volume; TLC, total lung capacity; sR_aw, specific airway resistance; DL_CO, diffusing capacity of the lung for carbon monoxide.</p><p>P-values are from a linear regression model, adjusted for age, sex, alcohol status, employment status, and body mass index.</p><p>**p<0.01 versus control;</p><p>***p<0.001 versus control.</p>#<p>p<0.05 GOLD 1 versus GOLD 2;</p>###<p>p<0.001 GOLD 1 versus GOLD 2.</p>†<p>GOLD 1, n = 40; GOLD 2, n = 62.</p>‡<p>GOLD 2, n = 61.</p

Subject disposition during the characterization phase of the study.

<p>IET, incremental exercise testing. *Since 104 control subjects had full characterization data available, only the first 104 patients with COPD, who were eligible for randomization, were age- and sex-matched with the controls for characterization data analysis.</p

Subject characteristics.

<p>Data are presented as mean ± standard deviation for continuous variables and number of patients (%) for categorical variables.</p><p>GOLD, Global Initiative for Chronic Obstructive Lung Disease; N/A, not applicable.</p><p>***p<0.001 versus control, using a two-sample <i>t</i>-test with unequal variance.</p>†<p>Drinks alcohol, but to an extent that would not interfere with participation in the trial.</p>‡<p>1 pack-year represents 20 cigarettes per day for 1 year.</p

Intensity ratings of (A) dyspnea and (B) leg discomfort versus work rate during incremental treadmill exercise.

<p>Data are shown as mean ± standard error. *p<0.05 GOLD 1 and GOLD 2 versus controls at a standardized work rate; ^#p<0.05 GOLD 1 versus controls (confidence intervals do not overlap indicating p<0.05).</p

Peak symptom-limited incremental treadmill exercise.

<p>Data are presented as mean ± standard deviation.</p><p>GOLD, Global Initiative for Chronic Obstructive Lung Disease; , oxygen uptake; , carbon dioxide production; , minute ventilation; MBC, maximum breathing capacity; Vt, tidal volume; <i>F</i>b, breathing frequency; Ti, inspiratory time; Ttot, total respiratory time; Ti_/Ttot, inspiratory duty cycle; IC, inspiratory capacity; Δ, change; IRV, inspiratory reserve volume; EELV, end-expiratory lung volumes; SpO₂, arterial oxygen saturation measured by pulse oximetry.</p><p>P-values are from a linear regression model, adjusted for age, sex, alcohol status, employment status, and body mass index.</p><p>*p<0.05 versus control;</p><p>**p<0.01 versus control;</p><p>***p<0.001 versus control</p>#<p>p<0.05 GOLD 1 versus GOLD 2;</p>##<p>p<0.01 GOLD 1 versus GOLD 2;</p>###<p>p<0.001 GOLD 1 versus GOLD 2.</p>†<p>GOLD 2, n = 62.</p

Operating lung volumes versus work rate during incremental treadmill exercise.

<p>End-expiratory lung volume (EELV) and end-inspiratory lung volume (EILV) measurements were significantly greater (p<0.05) throughout exercise in GOLD 1 and 2 compared with controls (p-values based on two-sample t-test with unequal variance). Data are shown as means. TLC, total lung capacity; IRV, inspiratory reserve volume; VT, tidal volume.</p