Clinical remission of severe asthma ‘achievable goal’ with mepolizumab

Key takeaways:

• Fewer patients achieved remission with mepolizumab when more stringent definitions including lung function were used.
• Remission rates accounting for an additional component ranged from 22% to 31%.

Patients with severe asthma achieved clinical remission based on a four-component definition with 52 weeks of mepolizumab, according to an abstract presented at the European Respiratory Society International Congress.

However, fewer patients achieved remission based on the four-component definition compared with a three-component definition, Cristian Domingo Ribas, PhD, professor of medicine at Universitat Autònoma de Barcelona, said during his presentation.

“Clinical remission is an emerging concept in the management of patients with severe asthma, which has in part been facilitated by the use of precision medicine for the treatment of chronic inflammatory diseases,” Ribas said.

Definitions for clinical remission of severe asthma at 52 weeks are evolving, the researchers wrote, adding that the three-component definition that they used includes freedom from oral corticosteroid use and exacerbations with an Asthma Control Test score of 20 or higher.

A post-hoc analysis of the real-world REDES study (n = 260) found that 37% (n = 96) of adults with severe asthma achieved clinical remission based on this definition with 52 weeks of treatment with 100 mg of mepolizumab (Nucala, GSK).

Due to the natural loss of lung capacity from increasing age, in addition to questions of how lung function remission components can be best defined, the inclusion of outcomes related to lung function in the definition of clinical remission of severe asthma is under debate, according to the researchers.

When the researchers added 80% or greater predicted post-bronchodilator (BD) FEV₁ measurements at week 52 as a fourth component to the definition of clinical remission for the 144 patients (75% women; mean age, 58.6 years) who had these data, the clinical remission rate dropped to 30% (n = 43).

Alternatively, the researchers considered four changes in post-BD FEV₁ as individual fourth components of the definition in 125 patients who had these data. Percentages of patients achieving clinical remission based on each of these additions included:

• 100 mL or greater improvement: 22% (n = 28);
• 0 mL or greater improvement: 27% (n = 34);
• 50 mL or less worsening: 30% (n = 38); and
• 100 mL or less worsening: 31% (n = 39).

The 50 mL loss of FEV₁ may reflect a loss that is similar to the natural loss of lung function that occurs each year among individuals who do not have lung disease, the researchers noted.

“This post-hoc analysis from the real-world study supports that clinical remission is an achievable goal in a subset of patients with severe asthma receiving mepolizumab,” Ribas said.

Also, the researchers said, the inclusion of a lung function parameter in the definition of clinical remission led to marginally fewer patients considered in remission compared with the three-component definition.

“This feeds into the discussion of whether lung function should be factored into the definition of clinical remission or not,” Ribas said.

If lung function is not included in definitions of clinical remission of asthma, the researchers suggested that it may be reserved as a validation factor.

“These findings support targeting clinical remission with mepolizumab as a realistic real-world target and should be used in the development of a standardized and validated definition in patients with severe asthma,” Ribas said.