Optimize Off-Label Use of Biologics and New Medications

Even “gold standard” therapies do not work equally well for all patients. Physicians are challenged continually to explore other options that may offer solutions for hard-to-treat cases. But questions remain as to which drugs might have indications beyond those that are FDA-approved, and which new medications may be worth prescribing despite open questions about their long-term risks and rewards.

Creating successful treatment plans around the off-label use of biologics and new medications provided the focus of a session conducted at the American Academy of Dermatology’s 2022 Annual Meeting by David Rosmarin, MD, FAAD, clinical investigator and vice-chair for research and education at Tufts Medical Center, Boston, Massachusetts, in collaboration with Adriane A Levin, MD, FAAD, director of the atopic dermatitis program at Brigham and Women's Hospital, and an instructor in dermatology at the Harvard Medical School, both based in Boston, Massachusetts.¹

The speakers highlighted strategies for optimizing the delivery of appropriate treatments for individual patients’ needs. Their review of the literature on off-label biologics use and new medications centered on TNF-alpha inhibitors, anti-IL-17 antibodies, anti-I-L23 biologics, dupilumab (Dupixent; Sanofi and Regeneron Pharmaceuticals), and apremilast (Otezla; Amgen).

“Unfortunately, it takes a lot of money and a lot of resources for a company to get an indication for medication,” Rosmarin said. “So, a lot of the time, the uses for medications aren’t consistent with the label.”

Dupilumab is one example, he said. “It’s currently approved for atopic dermatitis (AD), asthma, and chronic rhinosinusitis with nasal polyposis,” he noted. “But we see that it works with other conditions such as hand eczema or allergic contact dermatitis and patients who have HIV pruritis.”

There have also been recent studies which showed the drug’s effectiveness in treating chronic spontaneous urticarial and prurigo nodular as well, according to Rosmarin.

“Some other inflammatory disorders where it can be used include alopecia areata and Grover’s Disease,” he added. “Some evidence shows it can be combined with other psoriasis biologics if a patient has both psoriasis and atopic dermatitis simultaneously,” Rosmarin added. “It’s been used very recently for some rare genetic syndromes such as Hailey-Hailey disease, Job’s syndrome, and Netherton syndrome. Those are all exciting uses.”

Dupilumab is gaining some traction in bullous pemphigoid, an autoimmune blistering disorder occurring mostly in the elderly that, in Rosmarin’s view, lacks adequate treatments. He also noted recent cases in which this medication improved outcomes for patients with epidermolysis bullosa pruriginosa and pemphigus vulgaris.

“So, there has been a lot happening with the use of dupilumab for blistering disorders, but the most evidence in the blistering space has been with bullous pemphigoid,” Rosmarin said. “Currently there are case series regarding its efficacy in blistering disorders. In a case with 13 patients, at least 12 had some clinical improvement, with a little over half having complete clearance of both their blisters and itch: 75% having complete resolution of blisters, and 85% having some improvement in their itch. Many responded quite rapidly.”²

Dupilumab is also now being tested in a phase 3 program (Liberty-BP NCT04206553) for an indication in this, but that study will be a few years away, he added.

“A lot of this is very new literature, and some of it is not well-known. However, it’s important to know because sometimes we are faced with diseases where we need more options,” Rosmarin said. “We want treatments that are effective as well as safe for our patients and knowing about these alternative uses allows us to provide them to patients and help them get better.”

He added that most dermatologists will be faced with these rare cases at some point in practice and knowing about these solutions better prepares them for their treatment plans.

Turning to apremilast, an oral small-molecule phosphodiesterase 4 (PDE4) inhibitor with a multilevel immunomodulating mechanism of action, Rosmarin catalogued its on-label uses in moderate-to-severe plaque psoriasis, active psoriatic arthritis in adults and Behcet’s disease.

“In terms of other uses though, there are case series of it being used for pyoderma gangrenosum, hidradenitis suppurativa, seborrheic dermatitis, and also, one of my favorite uses, in lichen planus,” Rosmarin said.

He pointed out other possible additions to the seborrheic dermatitis armamentarium: topical roflumilast foam (ARQ-154; Arcutis Biotherapeutics), now in phase 3 trials (Stratum, NCT04973228), and topical crisaborole (Eucrisa; Pfizer), another PDE4 inhibitor that has been used off-label for treating this skin disorder.

“In terms of lichen planus, there are some patient cases demonstrating that apremilast can improve outcomes, and there’s also some evidence about the use of anti-IL-17, anti-IL-23 biologics for lichen planus as well,” Rosmarin said.

Anti-IL-17 is approved for psoriatic arthritis (PsA) and psoriasis within the dermatology space. Secukinumab’s (Cosentyx; Novartis) safety, tolerability, and efficacy were studied in a recent Phase 3 trial (NCT01989468), although results have not yet been published, Rosmarin noted. “Physicians also look to IL-17 for dissecting scalp cellulitis,” he noted.

Similarly for IL-23, there was a case for pyoderma gangrenosum, which Rosmarin noted can be a challenging disease to treat.

“The goal is for people to understand better the mechanism by which these medications work, so we have a broader view on how to treat some of these off-label diseases,” he said. “We want to understand their actions so we can think about them as more than just for their label.”

Disclosures:

David Rosmarin, MD, FAAD has received honoraria from AbbVie, Abcureo, Inc. AltruBio Inc., Boehringer Ingelheim, Bristol-Myers Squibb, Celgene Corporation, Concert Pharmaceuticals, Dermavant Sciences, Dermira, Incyte Corporation, Janssen Biotech. Kyowa Hakko Kirin Pharma, Inc., Lilly ICOS LLC, Novartis, Pfizer Inc., Regeneron, Sanofi, Sun Pharmaceutical Industries Ltd., and Viela Bio.

He has also been an investigator for AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Incyte Corporation, Janssen Biotech, Lilly ICOS LLC, Merck & Co., Inc, Novartis, Pfizer Inc., Regeneron, and Sanofi.

He has been a speaker for AbbVie, Amgen, Celgene Corporation, Janssen Biotech, Novartis, Pfizer Inc., Regeneron, and Sanofi.

And on the Data Safety Monitoring board for Concert Pharmaceuticals, Lilly ICOS LLC.

Adriane A Levin, MD, FAAD had no relevant disclosures.

References

1. Rosmarin D, Levin AA. Off-label use of biologics and new medications. Presented at: American Academy of Dermatology Association 2022 Annual Meeting; March 25 to 29, 2022, Boston, Massachusetts.

2.Abdat R, Waldman RA, de Bedout V et al. Dupilumab as a novel therapy for bullous pemphigoid: A multicenter case series. J Am Acad Dermatol. 2020 Jul;83(1):46-52. doi:10.1016/.js.2020.01.089. Epub 2020 Mar 13. PMID: 32179082.