Immune Modulation in the Spotlight at AAD 2018

Laird Harrison

February 12, 2018

SAN DIEGO — New ways to influence the immune system are leading to innovative treatments that will figure prominently at the upcoming American Academy of Dermatology (AAD) 2018 Annual Meeting.

"Whenever you have a new technology that emerges that comes out of decades of basic research, we have an explosion," said Hensin Tsao, MD, PhD, from Harvard University in Cambridge, Massachusetts, who will chair the late-breaker sessions at the meeting.

Immune system modulators fall into two broad categories, Tsao told Medscape Medical News. Some enlist the immune system to attack cancer, and others block aspects of the immune system to treat inflammatory diseases.

Most of the clinical trials being presented for the first time at this meeting address inflammatory conditions. "It used be topical and systemic steroids were the only way to go," Tsao explained. "Now we can pick apart specific molecules responsible for diseases."

Epidemiologic studies on the burden of melanoma and other skin cancers will also be presented. Merkel cell carcinoma, in particular, "is an area of increasing importance to dermatologists," said Margaret Chren, MD, from Vanderbilt University in Nashville, Tennessee. "More is known about its pathogenesis," she explained.

Dramatic Progress in Psoriasis

Researchers from AbbVie will present two phase 3 trials of risankizumab for moderate to severe plaque psoriasis. Risankizumab blocks interleukin (IL)-23, a key cytokine linked to chronic immune-mediated diseases, such as Crohn's disease, psoriatic arthritis, and ulcerative colitis. The plaque psoriasis trials compare risankizumab with ustekinumab (Stelara, Janssen Biotech) and placebo.

Another IL-23 inhibitor for plaque psoriasis — guselkumab (Tremfya, Janssen Biotech) — will get its time in the limelight when researchers present long-term efficacy data from the VOYAGE 2 phase 3 trial (NCT02207244). Guselkumab was approved by the US Food and Drug Administration (FDA) last year.

Data from the phase 4, randomized, double-blind, placebo-controlled crossover VIP-U trial on the effects of ustekinumab on vascular inflammation in psoriasis (NCT02187172) will be presented by Joel Gelfand, MD, from the University of Pennsylvania in Philadelphia. "This is a very timely topic in dermatology," Chren told Medscape Medical News. "Can you decrease overall inflammation by treating psoriasis?"

In the wake of such dramatic progress in treating psoriasis, Tsao said he is encouraged to see that treatments for atopic dermatitis are emerging along similar lines.

It's a terribly interesting time for dermatology research.

Results from a phase 2b trial of upadacitinib (ABT-494) in adults with moderate to severe atopic dermatitis uncontrolled with topical treatments will be presented by researchers from AbbVie. Upadacitinib selectively inhibits JAK1, which plays a role in a variety of immune-mediated inflammatory disorders. Phase 3 trials of upadacitinib in rheumatoid arthritis and psoriatic arthritis are currently underway, and the agent is also being investigated for Crohn's disease, ulcerative colitis, and ankylosing spondylitis.

A study of baricitinib, which targets JAK1 and JAK2, in adults with moderate to severe atopic dermatitis will be presented by Jonathan Silverberg, MD, PhD, from Northwestern University in Chicago. Baricitinib was approved for rheumatoid arthritis in the European Union last year, but FDA approval for that indication was denied and the regulator has requested further clinical data. It is also being studied for systemic lupus erythematosus. A phase 3 trial for psoriatic arthritis has been delayed.

In another investigation of atopic dermatitis, results from a phase 2a proof-of-concept study on ANB020, which inhibits IL-33, another pro-inflammatory cytokine, will be presented by Graham Ogg, BMBCh, from Oxford University in the United Kingdom. Studies have indicated that IL-33 is a central mediator of atopic diseases, including atopic dermatitis, food allergies, and asthma.

Other skin diseases are also benefiting from targeted inhibition of the inflammatory mechanism. Phase 3 results on apremilast (Otezla, Celgene) for Behcet's disease will be presented by Yusuf Yazici, MD, from New York University in New York City. Apremilast is a phosphodieasterase-4 inhibitor that decreases proinflammatory mediators and increases anti-inflammatory mediators. It has been approved by the FDA for psoriatic arthritis.

The education component of the meeting will cover a wide range of dermatologic topics, including controversies in vitamin D, commonly missed diagnoses, adverse effects related to cancer drugs, and ways to make use of the guidelines for psoriasis, acne, and atopic dermatitis.

"It's a terribly interesting time for dermatology research," said Chren. "Across the biomedical research spectrum, from the bench to the bedside, there is really exciting work."

Tsao is a consultant and medical advisory board member for Epiphany Dermatology. Chren has disclosed no relevant financial relationships.

Follow Medscape Dermatology on Twitter @MedscapeDerm and Laird Harrison @LairdH

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