Five severe conditions show positive response. More to come…
Biologic medications are being approved for and showing promise in the treatment of skin diseases other than psoriasis. Last year, the FDA approved the anti-IgE antibody omalizumab (Xolair, Roche/Genentech and Novartis) for the treatment of chronic idiopathic urticaria.
“Probably one of the biggest recent steps forward in dermatology was to have an approved biologic treatment for chronic idiopathic urticaria,” said Michael P. Heffernan, M.D., who is a clinical assistant professor of dermatology at Indiana University School of Medicine, Indianapolis, Ind., in private practice at the San Luis Dermatology and Laser Clinic and San Luis Obispo, Calif., and who led the Biologic Therapy in Dermatology beyond Psoriasis forum in March 2015, at the American Academy of Dermatology’s annual meeting in San Francisco.
Dermatologists are increasingly using the medications off-label for a range of skin conditions, including blistering and granulomatous diseases, according to Dr. Heffernan. In the vast majority of these diseases, the dosing regimen is the same as that used for psoriasis, he said.
In diseases such as pemphigus vulgaris, the off-label use of anti-B-cell therapies is gaining ground as an alternative or adjuvant therapy to systemic treatments.1
“There’s a great deal of data [looking at] the CD20 antibody rituximab for the treatment of autoimmune blistering diseases, such as pemphigus, but also pemphigoid, epidermolysis bullosa acquisita and mucous membrane pemphigoid 2,” Dr. Heffernan said.
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The medications have moved into clinical practice--in many cases, up towards the first line of treatment for these significant life-altering blistering diseases, he said. The biggest side effect is the cost and concerns about certain infections, including progressive multifocal leukoencephalopathy, which haven’t been seen in autoimmune blistering disease patients to date, according to Dr. Heffernan.
In a meta-analysis published earlier this year, researchers analyzed 30 studies with 578 patients, looking at the efficacy of different rituximab dosing regimens for treating pemphigus. More than three-quarters of the patients achieved complete remission after one cycle of the drug. Eighteen patients (3.3 percent of the total) developed serious adverse effects. While the researchers did not find significant differences in complete remission and relapse rates between patients treated with high-dose (near or≥ 2,000 mg/cycle) versus low-dose (< 1,500 mg/cycle) rituximab, they found the higher dosing was associated with a longer complete remission duration. Overall, the study’s authors said rituximab is efficacious and well-tolerated for treating pemphigus.3
Dr. Heffernan said he includes sarcoidosis, granuloma annulare and necrobiosis lipoidica diabeticorum under the umbrella of granulomatous diseases.
“As we know, you need tumor necrosis factor to make successful granulomas,” he said. “And medications that are highly effective at blocking tumor necrosis factor, or TNF blockers, like adalimumab and infliximab, have been shown in studies and in case reports and case series to be highly effective for the treatment of sarcoidosis, granuloma annulare and necrobiosis lipoidica diabeticorum. It looks like etanercept is not as effective for these diseases.”
There have been scattered case reports on the use of psoriasis biologics for atopic dermatitis, which, according to the literature, have not been terribly effective, Dr. Heffernan said. The hope, he said, is in medications in development that block IL-4 and IL-13. Dupilumab, an anti-IL-4Rα mAb in phase 3 trials, is one example.
“We could, within the year, have this and other drugs in the class marketed for the treatment of moderate to severe atopic dermatitis. And that could be a significant improvement to our therapeutic options as practitioners who care for people with moderate to severe atopic dermatitis. It’s one of those big medical needs in dermatology,” Dr. Heffernan said.
Anti-TNF medications have been around the longest and have the most developed safety profile among the biologics used in dermatology, according to Dr. Heffernan.
“There’s evidence that strong anti-tumor necrosis factor blockers, specifically the antibodies like infliximab and adalimumab, make a clinical difference in the treatment of patients with hidradenitis suppurativa. Adalimumab (Humira) is in phase 3 trials right now, which are looking at whether adalimumab will be approved for the treatment of hidradenitis,” he said. “So many practitioners in clinical practice regularly use infliximab and adalimumab for the treatment of hidradenitis, currently in an off-label fashion. So, it would be very helpful for us to have an indicated treatment for hidradenitis, which would be the first indicated treatment for the disease.”
There also is a small case series on the use of anti-TNF medications, as well as for the use of ustekinumab, in patients who suffer from pityriasis rubra pilaris.4
Most of the major advances in the targeted treatment of melanoma have been in biologic therapies, according to Dr. Heffernan.
“One of the first biologic treatments developed [and approved] for melanoma ipilimumab injection (Yervoy, Bristol-Myers Squibb) is for the treatment of unresectable or metastatic melanoma. It upregulates the immune system to fuel the immune response to the cancer,” he said.
Dr. Heffernan said he anticipates that, by 2025, there will be several biologic agents approved for the targeted treatment of specific skin diseases.
“As the familiarity with biologics has grown and the comfort with their safety profile has grown, dermatologists and other investigators have felt more and more comfortable studying biologics in some less common but still severe diseases,” he said. “That’s really gratifying because sometimes the use of these medications has taught us about the diseases, and has shown that sometimes there are safe and hopefully effective ways to treat people who suffer from these life-altering diseases.”
1. Daniel BS, Murrell DF, Joly P. Rituximab and its use in autoimmune bullous disorders. Dermatol Clin. 2011 Oct;29(4):571-5. http://www.ncbi.nlm.nih.gov/pubmed/21925000
2. Zhao CY, Murrell DF. Pemphigus vulgaris: an evidence-based treatment update.Drugs. 2015 Feb;75(3):271-84. doi: 10.1007/s40265-015-0353-6. http://www.ncbi.nlm.nih.gov/pubmed/25655250
3. Wang HH, Liu CW, Li YC, Huang YC. Efficacy of Rituximab for Pemphigus: A Systematic Review and Meta-analysis of Different Regimens. Acta Derm Venereol.2015 Apr 17. http://www.ncbi.nlm.nih.gov/pubmed/25881672
4. Di Stefani A, Galluzzo M, Talamonti M, Chiricozzi A, Costanzo A, Chimenti S.Long-term ustekinumab treatment for refractory type I pityriasis rubra pilaris. J Dermatol Case Rep. 2013 Mar 30;7(1):5-9. http://www.ncbi.nlm.nih.gov/pubmed/?term=Di+Stefani+A%2C+Galluzzo+M%2C+Talamonti+M%2C+Chiricozzi+A%2C+Costanzo+A%2C+Chimenti+S.
Disclosure: None (Note: Dr. Heffernan had ties to most of the companies making biologics but hasn’t for two to three years. Today, he is senior medical director for Eli Lilly and Company, but didn’t talk about Eli Lilly medications in this story.)