The AD Tx Revolution at ACAAI

Andrew F. Alexis, MD, MPH

“We can all appreciate that there's really been a revolution in our management of atopic dermatitis [AD] over the past decade with the emergence of targeted therapies,” Andrew F. Alexis, MD, MPH, asked attendees of the American College of Allergy, Asthma and Immunology (ACAAI) 2023 Annual Scientific Meeting in Anaheim, California. “Inhibitors of the JAK/STAT pathway has been a very valuable addition to our treatment armamentarium, generally offering very rapid and sustained results with respect to controlling the signs and symptoms of AD, especially itch reduction.”

Alexis, the vice-chair for diversity and inclusion for the Department of Dermatology and professor of clinical dermatology at Weill Cornell Medical College in New York City and member of the Dermatology Times editorial board, reminded attendees that there are 3 JAK inhibitors that are currently available and approved for patients 12 years and older: ruxolitinib 1.5% cream, abrocitinib, and upadacitinib. The 2 oral options (abrocitinib and upadacitinib) are indicated for moderate to severe refractory AD and are more JAK-1 selective, he explained. Both treatments also come in 2 doses, he said; the low dose should be used when starting treatment, and if there is not an adequate response, the higher dose may be used. For abrocitinib, that means initiating treatment with 100 mg po qd and increasing to 200 mg po qd after 12 weeks if the response is not adequate. He added that patients should start with 15 mg po qd for upadacitinib and increase to 30 mg po qd if the response is inadequate.

Research has shown that ruxolitinib 1.5% cream has “a highly significant response rate” when looking at when looking at IGA and EASI-75, Alexis said.¹ He added that more recent data showed the response was sustained even after a 44-week extension following the original 8-week study, all with a favorable safety profile. Approved for mild to moderate AD, Alexis said ruxolitinib 1.5% should be limited to a maximum 60g tube per week or a 100g tube every 2 weeks; the treatment area should not exceed 20% body surface area.

Similarly, data supports abrocitinib’s safety and efficacy when compared with placebo and dupilumab and looking at IGA and EASI-75, including the JADE COMPARE study.² Importantly, research also found a significantly better itch response than dupilumab at 2 weeks. He noted that while there are higher rates of nausea, acne, and herpes with abrocitinib compared to dupilumab, there are higher rates of conjunctivitis in dupilumab.

Upadacitinib also performed better than dupilumab and had similar safety profiles.³ Research found better improvement at week 16 with upadacitinib, he said. Acne and herpes were more common with upadacitinib than dupilumab, but dupilumab was associated with more conjunctivitis. However, Alexis noted there were no major cardiovascular or thromboembolic events.

Finally, Alexis discussed the black box warnings and how to address potential patient concerns. He outlined the study that formed the basis for the warnings; specifically, that involved older patients, different indication, and patients with at least 1 cardiovascular risk factor. In doing so, he said it is important to emphasize the different risk profile of your patient and those that were in the study.

“When communicating with our patients, it's helpful to provide the context of the warnings and highlight that the patient in front of us—let's say it's a 21 year old otherwise healthy individual with atopic dermatitis and no personal or family history of cardiovascular events—is in a difference risk group than the group that led to the warnings in the study,” Alexis explained.

On top of that, he lets patients know that he is going to be monitoring them for potential issues. “We're going to do bloodwork before we start and during treatment periodically depending on which drug and the individual patient,” he added.

Alexis is a fan of shared decision-making, especially when prescribing and choosing JAK inhibitors. He illustrated this idea with an example.

“There was a gentleman who came to my practice with moderate to severe atopic dermatitis,” he said. “He is approximately 40 years of age. He has associated post-inflammatory hyperpigmentation. He has failed other therapies in the past, and offered the range of systemic agents that are available today, including biologics and oral JAK inhibitors. Long story short, after all the discussion, he preferred oral treatment based on his aversion toward needles and the potential for a more rapid response with an oral JAK inhibitor.”

“We ordered the usual labs that I would in this context,” Alexis continued. “I do a CBC comprehensive metabolic panel. I look at hep B, hep C serologies, and lipids. It's also advisable that he gets his herpes zoster vaccine, the shingles vaccine, in advance. I confirm he has absolutely no risk factors for major cardiovascular events, thrombosis, malignancy, serious infection, and we proceed with abrocitinib, the oral JAK-1 selective inhibitor, at the starting dose at 100 milligrams once a day.

“And he shows a remarkable response in 12 weeks. Of course, within days to 2 weeks he was already experiencing improvement in itch. But as far as the other clinical signs of AD, we see very significant changes and even an improvement in that post-inflammatory hyperpigmentation.”

Overall, Alexis noted these medications offer patients another treatment option.

“Inhibitors of the JAK stat pathway have been a very valuable addition to our treatment armamentarium,” Alexis concluded, “generally offering very rapid and sustained results with respect to controlling the signs and symptoms of AD, especially itch reduction.”

References

1. Papp K, Szepietowski JC, Kircik L, et al. Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: Results from 2 phase 3, randomized, double-blind studies. J Am Acad Dermatol. 2021;85(4):863-872. doi:10.1016/j.jaad.2021.04.085

2. Bieber T, Simpson EL, Silverberg JI, et al. Abrocitinib versus Placebo or Dupilumab for Atopic Dermatitis. N Engl J Med. 2021;384(12):1101-1112. doi:10.1056/NEJMoa2019380

3. Blauvelt A, Teixeira HD, Simpson EL, et al. Efficacy and Safety of Upadacitinib vs Dupilumab in Adults With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial JAMA Dermatol. 2021;157(9):1047-1055. doi:10.1001/jamadermatol.2021.3023