Off-Label Prescribing Off Limits, Leaving Some Untreated

Maureen Salamon

March 27, 2020

One of the aphorisms in dermatology, according to Lawrence Eichenfield, MD, is that prescription pads have become suggestion pads.

Patients face consistent head-on refusals from insurers to fill off-label prescriptions for the many dermatologic conditions for which there are no approved therapies, Eichenfield, from the UC San Diego School of Medicine, told Medscape Medical News.

There is a chasm between the thousands of skin diseases that dermatologists treat and the number of effective therapies approved by the US Food and Drug Administration (FDA) to specifically target these conditions, according to a 2019 review.

This discrepancy is largely responsible for the major prevalence of off-label prescribing in dermatology, which was estimated in a previous study to range from 17% to 73% in the United States.

"It's a huge problem," compounded by the fact that "the methodology of getting drugs into patients' hands has markedly changed over the past decade," Eichenfield explained.

"I used to write a prescription and the patient could get it if I thought it was the best drug for that patient," he explained. "But now, what a patient ends up getting could be different. The interim step required by insurers, pharmacy-benefit managers, and others to check whether lower-cost drugs can be substituted becomes a speed bump — if not an actual cement wall — for the patient getting off-label medicines."

But dermatologists say the need for off-label options is as pressing as ever.

"Many treatments that are optimal are for uncommon conditions, so they're published in small numbers of patients and never get approved" by the FDA for that indication, said Mark Lebwohl, MD, from the Icahn School of Medicine at Mount Sinai Health System in New York City.

Small Numbers, No Regulatory Approval

Off-label drugs come to the rescue in these cases, he said, because approved drugs in dermatology are often effective for different conditions with similar underlying pathologies.

"When you have a drug approved for the inflammatory condition of psoriasis, for example, there's a high likelihood it will also work for atopic dermatitis and seborrheic dermatitis and a whole host of other inflammatory conditions," Lebwohl told Medscape Medical News.

Eichenfield, a pediatric dermatologist, said he routinely prescribes off-label drugs for common conditions such as vitiligo and alopecia areata, which have "no specific drugs approved for them." He often turns to standard anti-inflammatories indicated for other conditions or topical steroids that have no efficacy data in children but that "we know are pretty effective."

Off-label prescribing ends up becoming, to some degree, part of the art of medicine.

For rarer skin diseases with no approved therapies, such as ichthyosis or epidermolysis bullosa, Eichenfield said he thinks back to "how we were trained to treat them, based on the mentors we worked with, or looks at changing trends in practice."

"Off-label prescribing ends up becoming, to some degree, part of the art of medicine, but it creates both a burden on the doctor to know how to assess efficacy and risk of a medication if there isn't a good dataset," he said. However, "it's something you know can be the best thing for that patient, even if it's off-label."

One off-label drug Lebwohl said he often turns to is tacrolimus, a topical calcineurin inhibitor approved for atopic dermatitis in patients 2 years and older. High-quality evidence supports the use of calcineurin inhibitors for many other indications, including chronic hand dermatitis, oral lichen planus, and lichen sclerosus, according to a 2019 report.

"My most common use is in psoriasis when I don't want to use steroids, but also in vitiligo and a long list of conditions for which no one would do a trial," he added.

But when Eichenfield writes a prescription for a calcineurin inhibitor for a child younger than 2 years, he knows there is a high likelihood "that the patient isn't going to get the drug covered."

Battle Between Doctors and Insurers

This ongoing tug of war with insurers to cover off-label prescriptions feels especially pointless to both Eichenfield and Lebwohl, considering how common the practice is.

Off-label medications have been approved by the FDA and have been proven safe, so their use doesn't need to be justified to patients.

But "ethical considerations" come into play because "none of us wants to lie on our chart," Lebwohl said. "If we're using tacrolimus, we don't want to write that the patient has atopic dermatitis when they don't."

This dilemma can lead to arguments with insurance companies. "If the patient has even a little bit of eczema, we can justify writing that diagnosis. But most of my colleagues won't do that," he added.

A tool to generate "very helpful" appeal letters for dermatologists whose prior authorizations have been denied is available on the website of the American Academy of Dermatology, Lebwohl reported.

And there's reason for optimism, especially in pediatric dermatology, despite the discouraging payer response to off-label prescriptions, Eichenfield said.

"It's a positive time in a way, because there's been more recognition from regulatory agencies that unless there's a push toward testing specific drugs in adolescents and kids, we're left with off-label prescribing," he said. "There's a sense children should be included."

American Academy of Dermatology (AAD) 2020 Annual Meeting.

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