Beclometason / Formoterol / Glycopyrronium (1) – Trimbow®

• Clinical trials
  • For the benefit assessment, the pharmaceutical manufacturer draws on the results of the three-arm, randomised, controlled TRIGGER trial, in which the triple combination of beclometasone/formoterol/glycopyrronium (BDP/Form/Glyc) is compared with beclometasone/ formoterol (BDP/Form) and BDP/Form + tiotropium.

a) Adults with asthma whose treatment with medium-dose ICS/LABA therapy has been discontinued and who have experienced at least one asthma exacerbation in the past year

• An additional benefit is not proven.
• The pharmaceutical manufacturer has not submitted any data for the assessment of additional benefit, as it was unable to identify any suitable studies for comparison with the appropriate comparator therapy.

b) Adults with asthma who have had their high-dose ICS/LABA therapy discontinued and who have experienced at least one asthma exacerbation in the past year

• Overall, based on the data submitted, an additional benefit is not proven for beclometasone/formoterol/glycopyrronium compared with treatment with beclometasone/formoterol + tiotropium.
• mortality
  • No statistically significant difference was observed between the treatment groups for the endpoint of all-cause mortality.
• Morbidity – Severe asthma exacerbations
  • Severe asthma exacerbations were defined as a worsening of asthma symptoms requiring treatment with systemic corticosteroids for at least three days.
  • For the endpoint of severe asthma exacerbations, there was no statistically significant difference between the treatment groups.
• Morbidity – Asthma symptoms (recorded in a patient diary)
  • For the endpoint ‘asthma symptoms’, recorded via the patient diary, there was no statistically significant difference between the treatment groups.
• Morbidity – Health status (EQ-5D VAS)
  • For the health status endpoint, measured using the EQ-5D VAS, there was no statistically significant difference between the treatment groups.
• quality of life
  • No data on health-related quality of life were collected.
• Side effects – Adverse events (AEs)
  • During the study period, a comparable number of patients in the intervention arm (71.8%) and the control arm (73.2%) experienced at least one AE (adverse event).
• Side effects – Serious adverse events (SAEs)
  • It is not possible to evaluate the data on SAEs, as events relating to the primary outcome ‘asthma’ were included in the submitted analyses.
  • The pharmaceutical manufacturer has subsequently submitted analyses of SAEs excluding severe asthma exacerbations as part of its response. However, events relating to the ‘Asthma’ primary endpoint are still included in the analysis. Consequently, the data submitted regarding SAEs remain unusable.
• Side effects – discontinuation due to AEs and major adverse cardiovascular events (MACE)
  • For the endpoints of discontinuation due to AEs and MACE, there is no statistically significant difference between the treatment groups.
• Overall assessment / Conclusion
  • For the benefit assessment of beclometasone/formoterol/glycopyrronium in adults with asthma who have their high-dose ICS/LABA therapy discontinued and who have experienced at least one asthma exacerbation in the past year, results from the randomised, controlled TRIGGER trial on the endpoint categories of mortality, morbidity and side effects, compared with treatment with beclometasone/formoterol + tiotropium.
  • For the endpoint of all-cause mortality, there was no statistically significant difference between the treatment groups.
  • For the endpoints of severe asthma exacerbations, asthma symptoms and health status (measured using the EQ-5D VAS) within the morbidity category, there was also no statistically significant difference between the treatment groups.
  • Data on health-related quality of life were not collected.

Courtesy translation only, please refer to the German original.