Omalizumab benefits patients with moderate to severe allergic asthma regardless of BMI

Omalizumab benefited patients with moderate to severe allergic asthma regardless of their BMI, according to a study published in Annals of Allergy, Asthma & Immunology.

“There is the perception that patients who have higher BMIs and are considered obese may have other pathways and mechanisms of inflammation other than allergic inflammation,” Bob Geng, MD, assistant clinical professor at University of California San Diego School of Medicine, told Healio.

Bob Geng

“We wanted to see whether overweight and obese individuals who suffer from severe allergic asthma can also derive the same degree of therapeutic benefits from target precision medicine, such as omalizumab, aimed against moderate to severe allergic asthma,” continued Geng, who also is an allergist and immunologist at Rady Children’s Hospital-San Diego.

Omalizumab (Xolair; Genentech, Novartis) utilizes biomarker-guided and weight-based guidance on dosing, Geng said.

“We wanted to see whether weight-based guidance on dosing for precision medicine may play a role in relation to the degree of therapeutic benefits,” he added.

The researchers pooled data from a pair of randomized, double-blind, placebo-controlled studies of adults aged 18 to 75 years with moderate to severe allergic asthma.

Research began with a 4- to 6-week run-in period where all participants switched treatment to an inhaled beclomethasone dipropionate (BDP) at a dose at which they were stable.

Researchers then categorized participants based on BMI and randomly assigned them to receive omalizumab or placebo subcutaneously at 0.016 mg/kg or greater of body weight per international unit of total serum every 2 or 4 weeks based on body weight and total IgE at screening.

Of the 397 adults categorized as underweight/normal, 203 were randomly assigned to receive omalizumab (mean age, 40 years; 61.6% women; 94.6% white) and 194 to receive placebo (mean age, 38.6 years; 59.3% women; 91.8% white). Of the 330 categorized as overweight, 161 were randomly assigned to receive omalizumab (mean age, 43.4 years; 43.5% women; 88.2% white) and 169 to placebo (mean age, 41.3 years; 44.4% women; 91.7% white). Of the 268 categorized as obese, 140 were randomly assigned to receive omalizumab (mean age, 41.9 years; 64.3% women; 89.3% white) and 128 to placebo (mean age, 44.1 years; 71.1% women; 83.6% white). Each participant was symptomatic with moderate to severe asthma despite treatment with inhaled corticosteroids (ICS).

During the next phase, which involved 16 weeks of corticosteroid stability, participants maintained their BDP doses. The 12-week corticosteroid phase that followed involved tapering off BDP doses, subject to predefined criteria.

Across all BMI categories, participants treated with omalizumab saw consistently lower asthma exacerbation rates than participants treated with placebo. Relative reductions in exacerbation rates between the two groups increased with BMI, from –37.4% (95% CI, –69 to 26.8) among the patients with underweight or normal BMIs to –52.7% (95% CI, –78.4 to 3.7) among participants with overweight BMIs and –71.9% (95% CI, –86.9 to –39.5) among participants with obesity.

Similarly, the researchers found improvements in lung function across all BMI categories with omalizumab compared with placebo. After the corticosteroid stability phase, the least mean square (LSM) difference in FEV₁ between the groups was 76.2 mL (95% CI, 5.3-147.1) among the participants with underweight or normal BMIs, 98.1 mL (95% CI, 13.9-182.4) among the participants with overweight BMIs and 69.1 mL (95% CI, –18.9 to 157.2) among the participants with obesity.

All three BMI categories showed reductions in BDP dose as well, with no differences between the normal/underweight (LSM difference, 23; 95% CI, 15.7-30.3) and overweight categories (LSM difference, 22.5; 95% CI, 13.5-31.5) and numerically lower BDP dose reductions among the participants with obesity (LSM difference, 16.6; 95% CI, 5.8-27.3), although the researchers noted a large degree of overlap between the 95% CIs.

Compared with participants receiving placebo, participants assigned omalizumab experienced improvements in total asthma symptoms scores across all BMI categories as well, with slightly greater improvements among the underweight/normal and overweight categories than the participants with obesity, with largely overlapping 95% CIs. LSM differences after 16 weeks were –0.52 (95% CI, –0.82 to –0.22) in the underweight/normal category, –0.5 (95% CI, –0.8 to –0.2) in the overweight category and –0.39 (95% CI, –0.77 to 0) in the obese category.

There also were improvements in asthma quality-of-life questionnaire scores among the omalizumab participants compared with the placebo participants across all BMI categories. The participants with underweight/normal (LSM difference, 0.34; 95% CI, 0.16-0.52) and overweight (LSM difference, 0.34; 95% CI, 0.13-0.55) BMIs saw slightly greater improvements than those with obese BMIs (LSM difference, 0.15; 95% CI, –0.08 to 0.39).

“The most significant findings have to do with the fact that omalizumab provided benefit to patients regardless of their BMI. It was effective for patients who were on the normal weight range, as well as in the overweight and obese BMI ranges,” Geng said.

These results likely are due to the weight-adjusted dosing, Geng added, delivering significant impact to benefit these patients regardless of their BMI category.

Compared with placebo, the researchers concluded, treatment with omalizumab reduced asthma exacerbations and BDP doses while improving lung function, asthma symptom score and asthma-related quality-of-life scores in all BMI categories.

“It is important for physicians to think about all different mechanisms behind inflammation for their asthmatic patients. Oftentimes, weight can be a comorbidity as well as a complicating factor in managing people’s respiratory status and function,” Geng said.

These results show that clinicians can use targeted precision medicine aimed toward reduction of allergic inflammatory triggers confidently, even in patients with overweight or obesity, and in individuals who may have other complicating factors contributing to their respiratory condition, Geng said.

“The utilization of targeted precision medicine for the allergic inflammatory pathway can be highly beneficial to reduce symptoms and improve lung function in those individuals and overall improve their quality of life,” he said.

New research can continue to explore these areas, Geng said, such as prospective studies designed to validate this post-hoc analysis’ findings.

Also, Geng said, conventional therapy for asthma such as corticosteroids, both inhaled and systemic, may have an impact in increasing metabolic and weight-based complications.

“Use of targeted precision medicine may lead to decreased need for courses of systemic steroids, lower strength of maintenance inhaled steroids, and overall better exercise and activity tolerance in asthmatic patients,” he said. “Next steps could be to conduct studies to examine whether the usage of targeted precision medicine can help reduce the BMI for overweight and obese asthmatics.”