The promise of biologic therapy in dermatology

For patients with life-altering diseases, including psoriasis, biologic medications offer new hope for positive outcomes, including complete disease clearance, according to a panel of experts at the American Academy of Dermatology’s annual meeting in San Diego.

“Prescribing and managing patients on these drugs is something every dermatologist should be comfortable doing. It might require a little homework, but the rewards in patient outcomes and quality of life are more than worth it,” says panel member Michael P. Heffernan, M.D., a San Luis Obispo, Calif., dermatologist and the U.S. dermatology director for Probity Medical Research.

Dermatologists speaking during the AAD session “Controversies and Difficult Questions Concerning Biologic Therapeutics,” tackled topics including off-label indications, malignancy risk, biologic use for hidradenitis suppurativa and disparities in biologic utilization and access.

ACCESS ISSUES CONTRIBUTE TO DISPARITIES IN BIOLOGIC USE

There are differences and potential disparities in whether patients receive and stay on biologic treatments for skin diseases, including psoriasis, according to Junko Takeshita, M.D., Ph.D., University of Pennsylvania Perelman School of Medicine, Philadelphia.

Older Medicare beneficiaries with psoriasis are more likely to discontinue biologic therapy than younger beneficiaries. Women are more likely to discontinue biologic therapy than men. Black individuals with psoriasis are less likely to receive biologics for psoriasis than whites. Medicare beneficiaries with psoriasis, who don't have a low-income subsidy and, thus, have higher co-pays for medications, are less likely to receive biologics for psoriasis than those who have a low-income subsidy and generally have low out-of-pocket costs. Some of these differences may be biologically driven; others are likely not to be.

While some people have access to biologics, others might not. A few factors that impede access to biologics include access to healthcare, in general; access to physicians, who will take care of psoriasis and other skin conditions that warrant biologic treatment; access to physicians who will prescribe biologics; and financial access to the drugs.

“Financial access … is a major barrier to biologic treatment since, biologics are expensive. High out-of-pocket expenses for biologics definitely impact a patient's access to these costly medications,” Dr. Takeshita said.

 Awareness of these differences is the first step in ensuring that dermatologists and others provide equitable care for their patients, according to Dr. Takeshita.

“Understanding why these differences exist is the next essential step in trying to equalize the playing field for biologic treatment and is an active area of investigation for my research group. Until we know exactly why these differences exist, some general things that we can do to close some of these gaps include making sure that we offer all medically appropriate treatment options to our patients in a socio-culturally competent manner, and being aware of and offering supportive resources to patients who have greater difficulty accessing biologics,” she said.

BIOLOGICS AND CANCER

When it comes to malignancy risk, studies of all the biologics that are used as monotherapy for moderate-to-severe psoriasis are very reassuring, according to Bruce Strober, M.D., Ph.D, University of Connecticut Health Center, Farmington, Conn.

“In fact, with regard to either solid tumor cancers or lymphoma, there is no convincing evidence that biologic monotherapy used to treat psoriasis causes an increased risk. There are some studies that indicate the TNF-inhibitors might slightly increase the risk of cutaneous squamous cell carcinoma, though. I would place this risk as highest in those patients with a greater inherent risk for squamous cell carcinoma. When combined with other immunosuppressive medications, such as methotrexate, biologics might have a slightly higher risk for malignancy, but even these data are uncertain,” he said.

Dr. Strober says that outside the slightly increased risk for squamous cell carcinoma with the TNF inhibitors, the data don’t convincingly indicate that one biologic used as a monotherapy is inherently safer than another with regard to de novo solid tumor or lymphoma risk. 

For patients who are receiving TNF-inhibitors and who are inherently at high risk for squamous cell carcinoma, Dr. Strober conducts full body skin exams every six to 12 month.

Clinical trials and real-world registries support the assertion that malignancy risk for biologic therapies as monotherapy for psoriasis is negligible.

“The data are overwhelmingly comforting,” Dr. Strober says. “Patients receive biologic therapies indefinitely for a chronic disease, and, therefore, might develop a malignancy incidentally while receiving one of these drugs, but that doesn’t mean the drug is to blame.”

The rate for malignancy in psoriasis patients is about one case per 200 patients, for each year of follow-up, he says.

“Most of the drug companies describe malignancy risks from their clinical trials and from registries that follow patients long term. Some of these registries are independent of pharmaceutical company influence and, therefore, are more unbiased,” Dr. Strober says. 

BIOLOGICS AND HIDRADENITIS SUPPURATIVA

Dermatologists and their patients are in the midst of a renaissance in the understanding and treatment of hidradenitis suppurativa, according to Alexa B. Kimball, M.D., Harvard Medical School, Boston.

“There are several studies on at least five biologics that have now been published: anakinra, adalimumab, ustekinumab, infliximab, and etanercept. We are definitely refining and improving how we use them,” she said.

Currently, only adalimumab is FDA approved for hidradenitis suppurativa treatment. “In my community, it has meant that adalimumab is now fairly easy to get for patients. This approval has also opened up an interest from industry to develop drugs for this indication, so I expect to see more studies with other agents and that’s very exciting for patients,” Dr. Kimball said.

Adalimumab remains the drug with the best established dosing regimen and efficiency for hidradenitis suppurative. But there is a fair amount of experience and data for infliximab. Anakinra and ustekinumab are less studied. And etanercept doesn’t appear to have meaningful efficacy in this disease, she said.

More biologic treatments are expected for hidradenitis suppurativa. “They are coming fast and furious and offer new approaches for a group of patients with severe needs,” Dr. Kimball said.

BIOLOGICS OFF LABEL

The FDA has-approved biologic treatments for several diseases: psoriasis, psoriatic arthritis, atopic dermatitis, hidradenitis, chronic urticarial, and metastatic melanoma.

But there remain a number of significant life-altering dermatologic conditions that do not have an FDA approved biologic treatment, Dr. Heffernan said.

“For many of those conditions, we have very strong scientific data to support the safe and effective use of biologic medications,” he said.

Anti-tumor necrosis factor (TNF) antibodies are effective for pyoderma gangrenosa, cutaneous sarcoid, granuloma annulare, and pityriasis rubra pilaris. Ustekinumab is effective for pityriasis rubra pilaris and possibly pyoderma gangrenosa, Dr. Heffernan said.

There’s also data to suggest biologics might not be the answer for certain diseases. “There are a number of biologics that have been studied and shown to be ineffective for a number of dermatologic conditions. Most notably, etanercept has been shown to be ineffective in pyoderma gangrenosa and sarcoid. Ustekinumab has been shown to be ineffective in sarcoid,” he said.

DISCLOSURES

Dr. Heffernan is an investigator for AbbVie, Brickell Biotech, Celgene, Dermavant Sciences, Foamix, Incyte Corporation, Innovaderm Research, Janssen Pharmaceuticals, LEO Pharma, Merck Serono, Novartis Pharmaceuticals and DS Laboratories. He is a consultant and speaker for Eli Lilly and Company.

Dr. Kimball is a consultant and investigator for Abbvie; a consultant for Celtaxsys, Dermira, Merck & Co., Novartis and Janssen Biotech. And she is an investigator and receives fellowship program funding from Janssen Pharmaceuticals.

Dr. Strober is a consultant for AbbVie, Almirall, Amgen, Astra Zeneca, Boehringer Ingelheim, Celgene, Dermira, Galderma, Janssen, Leo, Eli Lilly, Leo, Medac, Menlo Therapeutics, Novartis, Pfizer, GlaxoSmithKline, UCB Pharma, Sun Pharma, Ortho Dermatologics/Valeant, Regeneron and Sanofi-Genzyme. He is an investigator for AbbVie, Celgene, Eli Lilly, Janssen, Merck, Boehringer Ingelheim, GlaxoSmithKline, Pfizer, Galderma and Sienna. Dr. Strober is scientific director for the CORRONA Psoriasis Registry. And the University of Connecticut receives grant support for its fellowship program from AbbVie and Janssen.

Dr. Takeshita received a research grant for investigator-initiated research from Pfizer.

REFERENCES

“S019 - Controversies and Difficult Questions Concerning Biologic Therapeutics,” American Academy of Dermatology 2018 annual meeting. Alexandra Boer Kimball, Bruce Elliot Strober, et al., et al. 9 a.m. - Noon, Saturday, Feb. 17.