Open-Label Data Suggests No Increased Risk of Infections with Long-Term Dupilumab Use

Lisa Beck, MD
Credit: University of Rochester Medical Center

Data from an open-label extension study suggests there was no association observed between use of dupilumab (Dupixent) and increased overall risk of infections among adult patients with moderate-to-severe atopic dermatitis.

Results of the study, which were presented at the Revolutionizing Atopic Dermatitis (RAD) 2024 Annual Meeting, provide insight into the effect pod dupilumab use on infection risk over a 5-year period among patients from the LIBERTY AD trial.¹

“Serious infection rates remained low and stable over the 5-year [open-label extension]. This report reinforces the known long-term safety profile of dupilumab from an infection perspective,” wrote investigators.¹

Dupilumab received initial approval from the US Food and Drug Administration for adult patients with adults with moderate-to-severe atopic dermatitis in March 2017 based on data from a clinical trial program of more than 2100 adults. As a result of the immunosuppressive nature of many therapies used in dermatologic conditions, particularly atopic dermatitis, risk of infections with use of dupilumab has been a focal point of many research efforts since initial approval.²

An open-label extension study of dupilumab, LIBERTY AD was comprised of patients who had participated in any dupilumab parent study. Per trial protocol, patients in the open-label extension received dupilumab 300 mg weekly and use of concomitant topical treatments for atopic dermatitis were allowed.^2,3

At RAD 2024, Lisa A. Beck, MD, Principal Investigator of the Beck Research Lab and Lowell A. and Carol A. Goldsmith Professor in Dermatology at the University of Rochester, and colleagues presented data from an analysis of the study examining risk of infections. With this in mind, Investigators designed their study to estimate the exposure-adjusted incidence rates (EAIR) of treatment-emergent and skin infections. For the purpose of analysis, investigators used the placebo arm of the 1-year LIBERTY AD CHRONOS trial, which allowed for use of topical corticosteroids, to serve as the control arm for the study.¹

In total, the study included 2677 individuals. Of these, 2207, 557, and 334 completed treatment through 52, 148, and 260 weeks of follow-up, respectively. The most common reasons for study withdrawal during the open-label portion were dupilumab approval/commercialization and patient withdrawal, which accounted for 58.7% and 18.0% of withdrawals, respectively.¹

Upon analysis, results indicated the EAIR of patients 1 or more treatment-emergent infections was lower in the open-label extension study than the study’s control arm (70.7 vs 107.0 per 100 person-years). Results of the 5-year analysis suggest 50 patients experienced 1 or more serious infections (0.9 per 100 person-years), 53 (0.9 per 100 person-years) had 1 or more severe infections, and 20 (0.3 per 100 person-years) experienced 1 or more infections resulting in permanent treatment discontinuation.¹

Analysis of skin infection rates demonstrated skin infections were reported by 535 patients (11.0 per 100 person-years), with the most common being non-herpetic skin infections (n=249; 4.6 per 100 person-years) and herpes viral infections (n=343 6.6 per 100 person-years). Further analysis suggested the EAIR for skin infections decreased throughout the open-label extension period, with rates of 17.2, 11.9, and 11.0 per 100 person-years observed at 1 year, 3 years, and 5 years of follow-up, respectively, which investigators pointed out was lower than the 29.5 per 100 person-years observed in the control arm.¹

“Long-term dupilumab treatment in adults with moderate-to-severe AD does not increase risk of systemic or cutaneous infections. Rates of treatment-emergent infections, including skin infections, in the [open-label extension] for up to 5 years were low, compared with patients receiving placebo plus topical corticosteroids in a 1-year study,” investigators added.¹

References:

1. ^{Beck LA, Simpson EL, Thaçi D, et al. Long-term dupilumab treatment is not associated with an increased overall risk of infections in adults with moderate-to-severe atopic dermatitis. Abstract presented at Revolutionizing Atopic Dermatitis 2024. Chicago, Il. June 08-10, 2024.}
2. ^{Office of the Commissioner. FDA approves New Eczema Drug Dupixent. U.S. Food and Drug Administration. March 28, 2017. Accessed June 10, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-eczema-drug-dupixent.}
3. ^{ClinicalTrials.gov. Open-label study of dupilumab in patients with atopic dermatitis - full text view. ClinicalTrials.gov. Accessed June 10, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT01949311.}