Andrew F. Alexis, MD, MPH
“We can all appreciate that there has truly been a revolution in our treatment of atopic dermatitis [AD] over the past decade with the emergence 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 been a very valuable addition to our treatment armamentarium, generally providing very rapid and sustained results in controlling the signs and symptoms of AD, especially the reduction of pruritus.”
Alexis, the vice chair for diversity and inclusion of 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 currently three JAK inhibitors available and approved for patients 12 years and older: ruxolitinib 1.5% cream, abrocitinib, and upadacitinib. The two oral options (abrocitinib and upadacitinib) are indicated for moderate to severe refractory AD and are more JAK-1 selective, he explained. Both treatments are also available in two doses, he said; the low dose should be used when initiating treatment, and if there is no adequate response, the higher dose can be used. For abrocitinib, this means initiating treatment at 100 mg po qd and increasing to 200 mg po qd after 12 weeks if response is inadequate. He added that patients should start with 15 mg po qd for upadacitinib and increase to 30 mg po qd if response is inadequate.
Research has shown that ruxolitinib 1.5% cream has “a very significant response rate” when looking at IGA and EASI-75, Alexis said.1 He added that more recent data showed that responses were sustained even after a 44-week extension from 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 of 60 g tube per week or a 100 g tube every 2 weeks; the treatment area should not exceed 20% of the body surface.
Similarly, data support the safety and efficacy of abrocitinib compared to placebo and dupilumab and looking at IGA and EASI-75, including the JADE COMPARE trial.2 Importantly, research also showed a significantly better itch response than dupilumab after 2 weeks. He noted that while abrocitinib has a higher rate of nausea, acne, and herpes compared to dupilumab, dupilumab also has a higher rate of conjunctivitis.
Upadacitinib also outperformed 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 with dupilumab, but dupilumab was more often associated with conjunctivitis. However, Alexis noted that there were no serious cardiovascular or thromboembolic events.
Finally, Alexis discussed black box warnings and how to address potential patient concerns. He outlined the research that formed the basis for the warnings; this mainly concerned older patients, various indications, and patients with at least one cardiovascular risk factor. In doing so, he said it is important to emphasize the different risk profile of your patient and that of those who participated in the study.
“When communicating with our patients, it is helpful to provide the context of the warnings and emphasize that the patient before us – let’s say is a 21-year-old, otherwise healthy individual with atopic dermatitis and no personal or family history of has cardiovascular events – in a different risk group than the group that led to the warnings in the study,” Alexis explained.
In addition, he informs patients that he will monitor them for possible problems. “We will do blood tests before we start and periodically during treatment, depending on the drug and the individual patient,” he added.
Alexis is a proponent of shared decision making, especially when prescribing and choosing JAK inhibitors. He illustrated this idea with an example.
“I had a gentleman who came to my practice with moderate to severe atopic dermatitis,” he said. “He is about forty years old. He has associated post-inflammatory hyperpigmentation. He has had failures with other therapies in the past and has been offered the range of systemic agents available today, including biologics and oral JAK inhibitors. Long story short, after all discussions he preferred oral treatment, due to his aversion to needles and the possibility of a faster response with an oral JAK inhibitor.”
“We ordered the usual labs that I would order 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 receive his herpes zoster vaccine, the shingles vaccine, in advance. I confirm that he has absolutely no risk factors for major cardiovascular events, thrombosis, malignancy, serious infections, and we continue with abrocitinib, the oral selective inhibitor of JAK-1, at the starting dose of 100 milligrams once daily.
“And he shows a remarkable response in twelve weeks. Of course, he experienced an improvement in the itching within a few days to two weeks. But regarding the other clinical symptoms of AD, we see very significant changes and even an improvement in post-inflammatory hyperpigmentation.”
Overall, Alexis noted that these medications offer patients another treatment option.
“Inhibitors of the JAK pathway are a very valuable addition to our treatment arsenal,” Alexis concluded, “and generally provide very rapid and sustained results in controlling the signs and symptoms of AD, especially the reduction of pruritus .”
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 versus 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