Three-year eczema data show sustained safety, efficacy

In a three-year, open-label extension study of adults with atopic dermatitis (AD), dupilumab (Dupixent, Sanofi and Regeneron) has performed as expected, with continued efficacy and no new safety signals.

“This is an important study because it’s the only long-term study that was conducted with dupilumab following phase 2 and 3,” says study co-author Robert Bissonnette, M.D. He is medical director at Innovaderm Research in Montréal.

Registry and real-world studies continue to be conducted, he says, but the LIBERTY AD OLE is the only post-phase 3 trial performed under controlled conditions, with regular follow-up visits and adverse-event (AE) reporting. The publication appeared online June 17 in the American Journal of Clinical Dermatology.

Investigators enrolled 2,677 patients from previous dupilumab clinical trials. All patients received subcutaneous dupilumab 300 mg weekly (after a 400 mg loading dose), except for a small group who received 200 mg weekly before a protocol change in December 2013.

When the study began, says Dr. Bissonnette, its sponsor did not know if the U.S. Food and Drug Administration (FDA) would approve a dose of 300 mg weekly or every two weeks. “The sponsor probably guessed that 300 mg would be the best dose. But in the end, when the data were analyzed, there was no significant difference between 300 mg every week versus every two weeks.” Accordingly, the FDA chose the latter dose. “In a sense, this makes the study even more interesting from a safety perspective because we’re looking at data where patients received a dose that is higher than the dose that is currently approved.”

At database lock in February 2019, 347 patients (13%) had completed through week 148. Overall, 1061 patients (39.6%) had completed the study, including safety follow-up, to various time points. Additionally, 291 patients (10.9%) were receiving ongoing treatment, and 1325 patients (49.5%) had withdrawn, most frequently due to study termination by the sponsor upon dupilumab’s approval. Few patients discontinued due to AEs or inefficacy — 109 (4.1%) and 57 (2.1%), respectively.

“Data from the study, which uses the as-observed method (including only patients still in the study at various intervals), shows that both in terms of Eczema Area and Severity Index (EASI) and symptoms measured by a Pruritus Numerical Rating Scale (NRS), the improvement is sustained over time.” Between weeks 100 and 148, mean EASI in the as-observed cohort declined from 2.6 to 1.4. Mean weekly average Pruritus NRS fell from 7.2 at baseline of the parent study to 3.0 by week 10, and 2.1 by week 148 of the extension study.

The most commonly observed treatment-emergent AEs included nasopharyngitis (28.1%), conjunctivitis (19.5%), AD (16.4%), upper respiratory tract infection (13.1%), oral herpes (12.4%), injection-site reactions (9.7%) and headache (8.1%). Exposure-adjusted incidence rates of these AEs were generally lower than in the one-year LIBERTY AD CHRONOS phase 3 trial.

“In my opinion,” says Dr. Bissonnette, “safety is the most important data that you want from open-label extension studies. The disadvantage of open-label extension studies from a safety perspective is that you don’t have a placebo arm to compare to.”

The only adverse event that occurred more commonly than what has been reported in the placebo-controlled CHRONOS study is conjunctivitis, he says. “This is a known possible adverse event that we see with dupilumab.” As in previous studies, most cases were mild and resolved with time or intraocular steroid treatment. “The bottom line is, there were no new safety issues or findings from this three-year study.”

Moreover, says Dr. Bissonnette, no significant new safety signals have emerged since dupilumab has been commercially available. “This is what we want as dermatologists. What I’ve seen and read in ‘real-life’ publications is in line with what we published.”

Reference:

1. Beck LA, Thaçi D, Deleuran M, et al. Dupilumab provides favorable safety and sustained efficacy for up to 3 years in an open-label study of adults with moderate-to-severe atopic dermatitis [Published online ahead of print June 17, 2020]. Am J Clin Dermatol. 2020;21(4):567-577.

Disclosure:

Dr. Bissonnette has been a consultant and/or received research support from AbbVie, Aquinox Pharmaceuticals, Arcutis, Asana, Astellas, Boehringer Ingelheim, Brickell Biotech, Dermavant, Dermira, Dignity Sciences, Eli Lilly, Galderma, Glenmark, GlaxoSmithKline-Stiefel, Hoffman-LaRoche, Kiniksa, Incyte, LEO, NeoKera, Pfizer, Ralexar Therapeutics, Regeneron, Sanofi Genzyme and Vitae. He also is a shareholder in Innovaderm Research.