Add-on dupilumab reduces OCS use in patients with steroid-dependent severe asthma

In patients with chronic dependence on oral corticosteroids (OCS) for severe asthma, long-term exposure to dupilumab supports sustained reduction in OCS dosage and improvement in clinical outcomes for up to 96 weeks, according to an analysis of the phase III LIBERTY ASTHMA TRAVERSE study.

“[In TRAVERSE,] dupilumab demonstrated the ability to sustain the reduced OCS dosage from the parent OCS-sparing study while maintaining a low exacerbation rate and improved lung function and asthma control,” said the researchers.

This analysis evaluated data from 187 patients (mean age 51 years, 59 percent female) initially enrolled in the 24-week LIBERTY ASTHMA VENTURE study who rolled over to the open-label extension TRAVERSE study. Dupilumab was administered at a dose of 300 mg Q2W for up to 96 weeks. The subgroups evaluated were those who received dupilumab in both studies (D/D arm; n=90) and those who received placebo in VENTURE and dupilumab in TRAVERSE (P/D arm; n=97). [Chest 2022;162:46-55]

OCS dosage

At VENTURE trial baseline, mean daily OCS dosages were 11.0 and 11.6 mg in the dupilumab and placebo arms, respectively. By week 0 of TRAVERSE, these dosages dropped to 3.1 and 6.4 mg in the respective D/D and P/D arms. These continued to drop at weeks 48 (2.2 and 4.9 mg) and 96 (1.2 and 3.0 mg).

“After rolling over to TRAVERSE, patients on D/D were able to maintain, or even decrease, their background OCS dosage,” the researchers explained. In the P/D arm, the reduction in background OCS dosage, though not as rapid initially as in the D/D arm, was sustained over time, they continued.

Efficacy, safety outcomes

More than three-quarters of participants did not experience exacerbations between weeks 0 and 48 (76 percent [D/D] and 81 percent [P/D]). By week 48–96, these exacerbation-free rates jumped to 90 percent and 92 percent, respectively.

At parent-study baseline (PSBL), mean prebronchodilator FEV₁ in the D/D and P/D arms were 1.53 and 1.62 L, respectively. By week 2 of TRAVERSE, P/D arm patients experienced rapid FEV₁ improvement after switching to dupilumab (mean change from PSBL, 0.25 L). By week 96, the mean changes in FEV₁ from PSBL were 0.25 and 0.36 L in the respective D/D and P/D arms.

These efficacy outcomes highlight the marked reductions in exacerbation rates and rapid improvements in lung function and asthma control among patients who initially had placebo and eventually transitioned to dupilumab, the researchers explained. The week-96 findings in both exacerbation and lung function parameters were comparable between arms.

The D/D and P/D arms had similar rates of serious treatment-emergent adverse events (AEs; 11 percent and 12 percent) and treatment cessation owing to AEs (6 percent vs 4 percent). “In general, the safety profile of VENTURE patients was similar in the D/D and P/D arms during TRAVERSE,” said the researchers. [N Engl J Med 2018;378:2475-2485; Lancet Respir Med 2021;10:11-25]

An add-on option to improve asthma control

About a third of patients with severe asthma depend on OCS for symptom management. [Med J Aust 2018;209:S18-S21; Chest 2020;157:790-804] However, OCS is insufficient for preventing exacerbations or maintaining lung function improvement and entails side effects. [Ann Rheum Dis 2009;68:1119-1124, Ann Allergy Asthma Immunol 2004;92:512-522] As such, there is a need for treatment alternatives that can improve asthma control and produce a durable OCS reduction effect.

“[Our findings] demonstrate that patients with severe OCS-dependent asthma treated with dupilumab can sustain reduction in OCS dose while also maintaining improvements in clinical outcomes,” said the researchers.

The findings also augment existing data supporting long-term maintenance of OCS reduction and sustained improvements in asthma exacerbation rates and lung function in this patient setting. [Respir Med 2020;176:106260; Allergy Asthma Proc 2021;42:235-242]