Abrocitinib demonstrates rapid efficacy in treating atopic dermatitis
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A 200 mg dose of abrocitinib met stringent efficacy endpoints among substantial portions of patients with moderate to severe atopic dermatitis, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.
Abrocitinib (Cibinqo, Pfizer) also outperformed dupilumab (Dupixent, Sanofi Genzyme/Regeneron) and placebo in these endpoints, the researchers wrote.
“We are in an exciting period for atopic dermatitis treatment. After a period of drought, we now have multiple new medications, and even new classes of drugs, to treat AD,” Peter A. Lio, MD, clinical assistant professor of dermatology and pediatrics at Northwestern University Feinberg School of Medicine, told Healio.
Janus kinase (JAK) inhibitors represent a very new and exciting class of drug, Lio said, adding that abrocitinib is one of two JAK inhibitors that are available for AD.
According to Lio, JAK inhibitors appear to have tremendous efficacy in at least three dimensions, including the rapidity of effect, the depth or magnitude of the effect, and their durability.
“This paper sought to dig deeper into the JADE COMPARE phase 3 study that had dupilumab, one of the more established systemic treatments for AD, initially approved in 2017, as an active comparator so that we could better understand the different profiles of these medications,” he said.
Study design, results
The JADE COMPARE study involved 541 patients with moderate and 296 with severe AD who received 100 mg (n = 238) or 200 mg (n = 226) of abrocitinib orally once each day, 300 mg (n = 242) of dupilumab subcutaneously every 2 weeks, or placebo (n = 131) for 16 weeks in addition to background medicated topical therapy.
Eczema Area and Severity Index (EASI) scores noting 50%, 75% and 90% improvement from baseline began to separate between patients taking 200 mg abrocitinib from the scores of the dupilumab and placebo groups between days 15 and 29.
Additionally, 25% of the abrocitinib 200 mg group, 18.7% of the abrocitinib 100 mg group, 9.7% of the dupilumab group and 3.9% of the placebo group achieved 100% improvements in EASI scores from baseline at week 16.
When evaluating the proportions of patients who met Investigator Global Assessment score, indicating that patients were clear of symptoms, rates were higher at week 16 for the abrocitinib 200 mg (14.9%) and 100 mg (12.6%) groups then the dupilumab (6.5%) and placebo (4.8%) groups.
The proportions of patients who achieved Dermatology Life Quality Index scores indicating minimal or no impact on quality of life included 29.7% in the abrocitinib 200 mg group, 21.6% in the abrocitinib 100 mg group, 24% in the dupilumab group and 10.6% in the placebo group.
At week 16, the abrocitinib 200 mg and 100 mg groups had –64.1% and –49.1% least square mean percent change from baseline in Peak Pruritus Numerical Rating Scale scores, whereas the dupilumab group had a –58.5% change and the placebo group had a –30.3% change.
Proportions of patients who reported minimal or no impact on the Night Time Itch Scale at week 16 included 57.1% of the abrocitinib 200 mg group, 44.5% of the abrocitinib 100 mg group, 46.1% of the dupilumab group and 31.9% of the placebo group.
Treatment-emergent adverse events were reported by 61.9% and 50.8% of the abrocitinib 200 mg and 100 mg groups, 50% of the dupilumab group and 53.4% of the placebo group, with common events including nausea, nasopharyngitis, conjunctivitis and acne, indicating safety and tolerability.
Conclusions, next steps
Lio said that there was nothing too surprising about these results, as physicians already are gaining some clinical experience with abrocitinib.
“But it certainly reinforces our thinking about abrocitinib and the JAK inhibitors,” he said. “They work very fast and are able to attain a level of improvement that is allowing us to, for some patients at least, actually set higher goals for therapy, and that is very exciting to me as a clinician.”
Noting the rapid response that abrocitinib provided in relieving itch and pain, which patients consider the most important factors in judging treatment response, the researchers concluded that it is an alternative for treating moderate to severe AD.
Most importantly, doctors need “to understand that there are new options for treating AD and that ‘a little bit better’ may not be all we have to offer anymore,” he said, although communication will be part of this process.
“We need to get the message out about these new medications, both to patients and clinicians,” he said.
Lio noted that these are powerful therapies, so the process needs to involve shared decision-making. The risks, although certainly surmountable, he continued, are real and must be understood.
“I believe that this is part of the virtuous cycle of drug development and that as we learn more about the disease, we are able to develop new drugs, and we continue to learn from those to better understand the disease, and so on,” he said.
As for now, he said, the treatment is effective.
“These data show that we can get a substantial group of patients much better, 90% better or even to ‘clear,’” he said. “And for some of my patients, I have seen that this is the first time they have been so much better in a very long time.”
For more information:
Peter A. Lio, MD, can be reached at peterlio@gmail.com.
Perspective
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Jonathan Silverberg, MD, PhD, MPH
The results are highly significant, but not surprising per se. We have already seen potent efficacy demonstrated across multiple phase 3 studies of abrocitinib.
This post-hoc study builds upon that evidence by showing that a substantial proportion of patients treated with abrocitinib are able to pretty much completely clear their disease signs and symptoms. Abrocitinib also demonstrates superior efficacy compared with dupilumab and is best differentiated from dupilumab when assessing these more robust endpoints.
Also, these results are in line with my real-world experience. Abrocitinib is a potent and fast-acting medication and achieves very deep clinical responses, particularly with the 200 mg dose.
I think these results raise the bar set in clinical practices and will hopefully prompt clinicians to aim higher when setting treatment goals. For far too long, we had so little to offer our patients with tougher cases of AD. We finally have a toolbox of modern therapies that work well in this disease, and clinicians need to better understand how to use them.
It would be great if we had clinical features or biomarkers that can predict up front which patients will achieve these remarkable clinical responses of signs and symptoms. There are many research groups around the world working on these questions as we speak.
Perspective
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This study adds to the literature of relatively newly approved systemic agents, with a “drill down” on time to response of several outcomes measures in a study of the JAK inhibitor abrocitinib at higher and lower doses compared with standard doses of the biologic IL-4 alpha receptor blocker dupilumab.
Results from the JADE COMPARE study have been previously published, and this paper shows more rapid response of high-dose abrocitinib in multiple “harder endpoints” (more stringent outcomes) vs. lower doses of abrocitinib and dupilumab.
It was not unexpected that both drugs at any dose are remarkably (and of course statistically) better than placebo, even with the concurrent use of topical prescription agents (corticosteroids, calcineurin inhibitors or PDE4 inhibitors).
The most impressive data are the rapidity and extent of responses with the 200 mg dosing of abrocitinib, some differential time response in some parameters comparing 100 mg of abrocitinib vs. dupilumab, and some similar responses.
These results are consistent with my experiences. This study also shows the benefits that abrocitinib can bring with speediness of response. But it additionally displays that dupilumab at standard dosing seems to be comparable in many endpoints with longer periods of use.
An interesting question is whether, in select patients, short durations of initiation of higher-dose abrocitinib over several weeks, with a decrease in dosing from 200 mg to 100 mg, would allow the profound, speedy response, perhaps with retention of the effects.
However, this approach is not consistent with the verbiage in the FDA-approved prescribing information, which suggests initiation with the 100 mg dosing. Further studies of such a dosing regimen (starting high, moving lower) would be helpful to assess both efficacy and safety.
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