Serious asthma events with mometasone furoate plus formoterol compared with mometasone furoate

Abstract

Background: The safety of long-acting b-agonists added to inhaled corticosteroids for the treatment of persistent asthma has been controversial. Objective: We sought to determine whether administering formoterol in combination with mometasone furoate increases the risk of serious asthma outcomes (SAOs) compared with mometasone furoate alone. This clinical trial is registered as NCT01471340. Methods: We conducted a 26-week, randomized, double-blind trial in adolescent and adult patients (> _12 years) with persistent asthma in 35 countries with the primary objective of evaluating whether mometasone furoate-formoterol increases the risk of SAOs (adjudicated hospitalization, intubation, or death) compared with mometasone furoate alone. The key efficacy end point was asthma exacerbation (composite of hospitalization of > _24 hours, emergency department visits of <24 hours requiring systemic corticosteroids, or use of systemic corticosteroids for > _3 consecutive days). Results: Among 11,729 patients (mometasone furoateformoterol, n 5 5,868; mometasone furoate, n 5 5,861), a total of 81 SAOs, all asthma-related hospitalizations, were observed in 71 patients: 45 events from 39 patients receiving mometasone furoate-formoterol and 36 events from 32 patients receiving mometasone furoate. The hazard ratio for the first SAO in the mometasone furoate-formoterol versus mometasone furoate group was 1.22 (95% CI, 0.76-1.94; P 5 .411). Asthma exacerbation occurred in 1,487 patients: 708 receiving mometasone furoate-formoterol and 779 receiving mometasone furoate. The hazard ratio for the first asthma exacerbation in the mometasone furoate-formoterol versus mometasone furoate group was 0.89 (95% CI, 0.80-0.98; P 5 .021). Conclusions: The addition of formoterol to mometasone furoate maintenance therapy did not increase the risk of serious asthma-related events and reduced the risk of asthma exacerbation.

Safety of As-Needed Budesonide-Formoterol in Mild Asthma: Data from the Two Phase III SYGMA Studies

“…Large clinical safety studies of budesonide-formoterol and other approved ICS-LABA combinations given as maintenance therapy, initiated by the US FDA [26], have dispelled any lingering safety concerns (or misperceptions) relating to serious asthma-related AEs with LABA treatment when taken with an ICS from the same device [27][28][29][30]. The FDA subsequently removed the boxed warning from all approved ICS-LABA combinations [31].…”

Cardiovascular safety of mometasone/indacaterol and mometasone/indacaterol/glycopyrronium once-daily fixed-dose combinations in asthma: pooled analysis of phase 3 trials

“…Nevertheless, findings from the phase 2 study provide important supporting information on cardiovascular safety of the MF/IND fixed-dose combination in asthma. In 2010, the US Food and Drug Administration (FDA) mandated that companies marketing LABAs for asthma perform 26-week randomized trials of their ICS/LABA products versus the respective ICS controls, with the primary endpoint of asthma-related intubation or death [22][23][24][25]. Because the cause of death was described for all fatal cases, the incidence of cardiovascular death can be quantified based on the published data (Supplementary Table 9).…”

Outpatient management of asthma in adults: A snapshot of the 2020 GINA report

“…In summary, these trials found that the ICS-LABA combinations were effective in reducing asthma exacerbations requiring corticosteroids and did not signifi cantly increase the risk of serious adverse asthma outcomes. [4][5][6][7] Despite the removal of the boxed warning, no ICS-LABA combination has an FDAapproved indication for treating acute bronchospasm on an as-needed basis, as the GINA 2019 guidelines recommended. 8…”