Anti-IL-5 Biologics Effective For Up To Two Years In Severe Asthma, But Residual Disease Remains

More than 80% of patients with severe asthma responded to anti-IL-5 biologics in a two-year follow-up study, but 69% experienced persistent airflow obstruction, uncontrolled asthma symptoms and other signs of residual disease.

"Anti-IL-5 biologics for severe eosinophilic asthma cause life-changing positive effects, with an increase in quality of life and a reduction in exacerbations and use of oral corticosteroids," Dr. Katrien Eger of the University of Amsterdam told Reuters Health by email. "Still, the majority of patients suffer from residual disease manifestations, such as impaired lung function, uncontrolled nasal polyposis and inability to completely discontinue oral corticosteroids."

"Therefore," she said, "our advice to clinicians would be to: check and double-check compliance with inhaled corticosteroid/long-acting beta-agonist therapy (because some) patients decrease or stop their inhaler therapy when experiencing beneficial effects of biologics. Consider adding a long-acting muscarinic antagonist, intensifying topical corticosteroid therapy for the nose and sinuses, check morning cortisol levels, and consult an endocrinologist in case of adrenal insufficiency."

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Dr. Eger and colleagues analyzed real-life data from the multicenter Registry of Adult Patients with Severe asthma for 22 Optimal DIsease management (RAPSODI) for 114 patients (median age, about 66 at baseline; about half men) with severe eosinophilic asthma treated with different anti-IL-5 biologics (mepolizumab, reslizumab, benralizumab) for more than two years.

"Super-responders" were defined as those who showed no residual disease manifestations at the two-year follow-up; "partial responders" experienced residual disease; and "non-responders" discontinued anti-IL-5 treatment <2yr because of clinical worsening.

As reported in the Journal of Allergy and Clinical Immunology in Practice, at follow-up, 14% of patients were super responders, 69% partial responders, and 11% non-responders.

Overall, non-responders could not be distinguished from the other groups by any baseline characteristics, although there was a trend towards lower blood eosinophils and more frequent asthma that started under age 18.

A regression analysis did not identify significant predictors of non-response. However, after adjustment for age and sex, super-responders had a significantly shorter duration of asthma (adjusted odds ratio, 3.572) and a higher FEV1 at least 80% predicted (aOR, 3.708) compared with other patients, and tended to have a lower BMI (aOR, 2.675), asthma that had started in adulthood (aOR, 5.961), and absence of nasal polyps (aOR, 2.675).

Further, FEV1 80% predicted (aOR, 3.7) and asthma duration (aOR, 3.5) were predictors of super-response.

Switches between anti-IL-5 biologics occurred frequently (41%). The most common residual disease manifestations included impaired lung function (59%), uncontrolled sino-nasal disease (58%) and uncontrolled asthma symptoms (48%).

Dr. Eger said, "In many patients with severe asthma, anti-IL-5 biologics do not cover all the inflammatory pathways that have been activated. For that. we may have to wait for future effective therapies that have a broader anti-inflammatory action and minimal adverse effects."

Dr. Osita Onugha, an assistant professor of thoracic surgical oncology at John Wayne Cancer Institute at Providence Saint John's Health Center in Santa Monica, California, commented in an email to Reuters Health, "Improved treatments for severe asthma are on the horizon. In patients with difficult to control asthma, (anti-IL-5 biologics) would be a reasonable approach to improve the management of symptoms."

Like the authors, he noted, "It is not clear why some people were non-responders and others were partial or super-responders. Therefore, we cannot accurately predict who is most likely to have benefit from the medication, although it is clear that most people receive some benefit."

The Registry of Adult Patients with Severe asthma for 22 Optimal DIsease management (RAPSODI) is financially supported by an unrestricted grant from GSK, Novartis Pharma, AstraZeneca, Teva and Sanofi. None of these sources had a role in this specific study.

—Marilynn Larkin

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