by Andrew F. Alexis, MD, MPH
“We can all appreciate that there has really been a revolution in our management of atopic dermatitis [AD] over the past decade with the advent of targeted therapies,” Andrew F. Alexis, MD, MPH, asked attendees at the American College of Allergy, Asthma and Immunology (ACAAI) 2023 Annual Scientific Meeting in Anaheim, California. “Inhibitors of the JAK/STAT pathway have made significant additions to our treatment arsenal, generally offering very rapid and durable results in controlling the signs and symptoms of AD, particularly a reduction in itching.”
Alexis, vice chair of diversity and inclusion for the Department of Dermatology and professor of clinical dermatology at Weill Cornell Medical College in New York City and a member of the Times of dermatology editorial board, remind attendees that there are 3 JAK inhibitors currently available and approved for patients 12 years of age 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 insufficient response, the higher dose may be used. For abrocitinib, this means starting treatment with 100 mg po qd and increasing to 200 mg po qd after 12 weeks if the response is inadequate. He added that patients should start at 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 “very significant response rate” when looking at IGA and ESI-75, Alexis said.1 He added that later data showed that the response was sustained even after a 44-week extension after the original 8-week study, with each having a favorable safety profile. Approved for mild to moderate AD, Alexis said ruxolitinib 1.5% should be limited to a maximum of 60g tube per week or 100g tube every 2 weeks; the treatment area should not exceed 20% of the body’s surface area.
Similarly, data support the safety and efficacy of abrocitinib compared to placebo and dupilumab and looking at IGA and ESI-75, including the JADE COMPARE study.2 Importantly, research also found that itch had a significantly better 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 that there were no major cardiovascular or thromboembolic events.
Finally, Alexis discussed black box warnings and how to address concerns patients may have. He outlined the study that underpinned the warnings; specifically, related to elderly patients, different indications, and patients with at least 1 cardiovascular risk factor. In doing so, he said it is important to emphasize the different risk profile of patients and those in the study.
“When we’re communicating with our patients, it’s helpful to provide the context of the warning and highlight that the patient in front of us is—let’s say an otherwise healthy 21-year-old with atopic dermatitis and no personal or family history of cardiovascular events. in a difference risk group than the group that caused the warnings in the study,” explained Alexis.
In addition, he informs patients that he is going to monitor them for potential issues. “We are going to do blood work before we start and periodically during the treatment depending on the drug and the individual patient,” he said.
Alexis is a fan of shared decision making, especially when ordering 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’s about 40 years old. It has associated post-inflammatory hyperpigmentation. Other therapies had failed in the past, and offered the range of systemic agents available today, including biologics and oral JAK inhibitors. Long story short, after all the discussion, he preferred oral treatment based on his preference for needles and the possibility of a faster response with an oral JAK inhibitor.”
“We ordered the normal labs I would do in this context,” Alexis continued. “I do a comprehensive CBC metabolic panel. I look at hep B, hep C serologies, and lipids. It is also advisable that he receives his herpes zoster vaccine, the shingles vaccine, in advance. I confirm that he has no risk factors for major cardiovascular events, thrombosis, malignancy, serious infection, and we continue with abrocitinib, the selective oral JAK-1 inhibitor, at the initial dose of 100 milligrams once a day .
“And it shows a great response in 12 weeks. Of course, within days to 2 weeks he was already experiencing an improvement in the itch. But as far as the other clinical signs of AD, we see significant changes and even improvement in that post-inflammatory hyperpigmentation.”
Overall, Alexis noted that these medications offer patients another treatment option.
“Stat JAK pathway inhibitors have been a great addition to our treatment arsenal,” Alexis concluded, “typically offering very rapid and lasting results in controlling the signs and symptoms of AD, particularly a reduction in itching.”
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 English 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 Dermol. 2021; 157(9): 1047-1055. doi: 10.1001/jamadermatol.2021.3023
