Dupilumab Outcomes Stable at End of Open-Label Atopic Dermatitis Study

WASHINGTON – The LIBERTY AD open-label extension study of dupilumab is closing after 5 years with the small number of remaining patients showing stable and sustained improvements in skin lesions and pruritus and no new emergent side effects, Lisa Beck, MD, reported during a late-breaking session at the annual Revolutionizing Atopic Dermatitis conference.

Other recent research on the biologic has shown that it improves lesional skin barrier function and rapidly reduces the abundance of Staphylococcus aureus on lesional skin, Dr. Beck, professor of dermatology at the University of Rochester (N.Y.), said during another session at the meeting on long-term control of AD. Dr. Beck directs a laboratory at the University of Rochester Medical Center that focuses on understanding AD and is involved in the National Institute of Allergy and Infectious Diseases (NIAID)-funded Atopic Dermatitis Research Network (ADRN).

The LIBERTY AD open-label extension (OLE) study was a phase 3 trial of 2,677 adults with moderate to severe AD who had participated in previous dupilumab clinical trials and were treated with 300 mg dupilumab weekly or every other week. Concomitant treatments were permitted, including topical corticosteroids and topical calcineurin inhibitors. (The proportion of patients dosed on an every-other-week or weekly dosing schedule was not available.)

Of 334 patients (12.5%) who remained in the trial at week 260, or 5 years, 88.9% achieved at least a 75% improvement in lesion extent and severity (Eczema Area and Severity Index [EASI]-75), and 76.2% achieved an EASI-90. The proportion achieving at least a 4-point reduction in the Peak Pruritus Numerical Rating Scale (NRS) or a score of 0 was 66.5%. At 5 years, improvements "seem very stable," with "no loss in efficacy," Dr. Beck said.

The majority of patients who withdrew from the open-label extension trial did so because the study was terminated at their site or because of the drug's approval and commercialization – not for a medical reason, Dr. Beck said. Over the course of the extension trial, 4% of those enrolled withdrew because of adverse events and about 2% withdrew because of lack of efficacy.

Safety of dupilumab

The extension trial lacked a control arm, so Dr. Beck and her colleagues compared safety results to those in the final data set for patients in the LIBERTY AD CHRONOS study who received dupilumab 300 mg weekly with concomitant corticosteroids. The CHRONOS study was a 1-year randomized, double-blinded placebo-controlled phase 3 trial.

The exposure-adjusted incidence rate of severe treatment-emergent adverse events (TEAE) was lower at the close of the extension trial (5 patients/100 patient years [PY]) than at the end of the CHRONOS study (5.9 patients/100 PY). The incidence of serious adverse events related to treatment was 0.6 patients/100 PY in the final open label extension study data set, compared with 0.7 patients/100 PY in the CHRONOS final data set.

Adverse event rates "are really, if anything, slightly less in the OLE study versus the CHRONOS study, which was 1 year of treatment," Dr. Beck said. And "no new adverse events have emerged."

During a question and answer period, Dr. Beck pointed out that existing and future "real world" registries of patients on dupilumab and other new therapies will better inform dermatologists of adverse events than clinical trials have done.

Ocular surface disease

In a separate presentation on the safety of biologics, Andrew Blauvelt, MD, MBA, of the Oregon Medical Research Center, Portland, said that in routine care, ocular surface disease is the most predominant side effect associated with dupilumab. "We don't know the mechanism of action. But it's not infectious, it's not pink eye, and importantly, it's not allergic conjunctivitis," he said, noting that the spectrum of disease ranges from dry eye and eye itching to "frank conjunctivitis" and keratitis.

Most cases are mild to moderate and can often be managed with lubricating eye drops and periodic use of corticosteroid eye drops. Co-management with an ophthalmologist is often advisable, he said.

Dupilumab-associated erythema/eczema of the face was "not seen much" in clinical trials but is also being reported in the literature, largely by European researchers, Dr. Blauvelt said. "We hear a lot about red face, but I don't think it's much of an issue," he said. "Most of the time, in my experience, it will [reflect] breakthrough residual AD, and I like to treat it with non-steroidal topicals."

Occasionally, the withdrawal of steroids or allergic contact dermatitis are at play, Dr. Blauvelt said. "If you see red face in a person on dupilumab, use your clinical prowess, do a differential diagnosis, and treat accordingly."

Effect on S. aureus

The vast majority of adults with moderate to severe AD have skin colonization with S. aureus, Dr. Beck said during the session on long-term control of AD. The presence of S. aureus in skin cultures correlates strongly with AD severity, type 2 immunity polarization, skin barrier disruption, and allergen sensitization, she said.

"So if we could do something to get rid of the staph and keep it away, one might imagine that would help" control the AD disease process, she said.

An ADRN study evaluated S. aureus in the skin of 71 patients who were randomized to receive dupilumab or placebo and found a "profound" effect of the biologic. "We were truly shocked by how quickly we saw a reduction in Staph aureus ... in lesional skin as early as 3 days" into treatment with dupilumab, she said of the unpublished findings. "And there is a pretty nice association with improvement in disease severity."

Dr. Beck reported consultancy/advisory board work with Regeneron, Sanofi/Genzyme, among other disclosures. Dr. Blauvelt reported consultancy/advisory board work for Regeneron and Sanofi Genzyme and has received speakers bureau/honoraria for non-CME work for Regeneron and Sanofi, among other disclosures.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

© 2023  Frontline Medical Communications Inc.

Cite this: Dupilumab Outcomes Stable at End of Open-Label Atopic Dermatitis Study - Medscape - Jun 06, 2023.