Dupilumab safe for long-term use to treat moderate to severe asthma

Key takeaways:

• The median treatment duration was 309 days, with 7.4% of patients receiving more than 958 days of treatment.
• The exposure-adjusted event rate for serious adverse events was 6.9 per 100 patient-years.

Dupilumab appeared safe for long-term use among patients with moderate to severe asthma or oral corticosteroid-dependent severe asthma, according to data from the TRAVERSE continuation study.

“The proportion of patients reporting treatment-emergent adverse events throughout the TRAVERSE continuation study was lower than that observed in the parent studies,” Jorge F. Maspero, MD, medical director of Fundación CIDEA in Buenos Aires, Argentina, and colleagues wrote.

The single-arm, multicenter, open-label 3b study included 393 participants (mean age, 52.1 years; 58.8% female) with moderate to severe asthma or oral corticosteroid-dependent severe asthma who had completed the TRAVERSE open-label extension following their participation in a prior phase 2b trial or the phase 3 LIBERTY ASTHMA QUEST or LIBERTY ASTHMA VENTURE studies of dupilumab (Dupixent; Sanofi, Regeneron).

To determine long-term safety of dupilumab, all participants received 300 mg doses every 2 weeks for up to 144 weeks, or 3 years.

Researchers evaluated treatment-emergent adverse events, serious adverse events and adverse events of special interest by calculating incidence rates and exposure-adjusted event rates per 100 person-years.

Overall, 374 of the patients (95.2%) completed study treatment and 19 discontinued treatment for a cumulative exposure to dupilumab of 431.7 patient-years and a median treatment duration of 309 days (range, 25-1,047). About half of participants received treatment for at least 286 days and 29 received treatment for more than 958 days.

Throughout the study, 214 (54.5%) participants, experienced at least one treatment-emergent adverse event — the most common of which were asthma (13.7%), nasopharyngitis (8.4%), COVID-19 infection (6.4%), upper respiratory tract infections (3.8%) and bronchitis (3.6%) — for an event rate of 171.4 per 100 person-years.

Thirty-seven (9.4%) participants experienced at least one treatment-emergent adverse event that the researchers considered to be treatment-related, for an event rate of 29 per 100 person-years. These included decreased platelet counts, injection-site erythema, decreased neutrophil count and decreased white blood cell count. The researchers reported that none of these events led to treatment discontinuation.

Twenty-two participants (5.6%) experienced at least one serious adverse event during the trial, with an exposure-adjusted event rate of 6.9 (95% CI, 5.21-9.03) per 100 patient-years. The exposure-adjusted event rate for the most common serious adverse events were asthma exacerbation (1.2; 95% CI, 0.46-2.2), COVID-19 (0.7; 95% CI, 0.23-1.62) and COVID-19 pneumonia (0.7; 95% CI, 0.23-1.62).

Twenty-four patients (6.1%) experienced adverse events of special interest, with an exposure-adjusted event rate of 6 (95% CI, 4.4-7.99) per 100 person-years. These included influenza (1.6; 95% CI, 0.81-2.78), COVID-19 pneumonia (0.9; 95% CI, 0.35-1.97), herpes zoster (0.7; 95% CI, 0.23-1.62) and oral herpes (0.7; 95% CI, 0.23-1.62).

“Here, it is of note that the safety profile and tolerability observed during long-term treatment for an additional 3 years in the TRAVERSE continuation study was consistent with that initially observed for up to 3 years throughout the phase 2b, QUEST, VENTURE, and TRAVERSE studies, thus affirming the overall long-term safety and tolerability of dupilumab,” the researchers wrote.