PracticalDermatology

Rinvoq (upadacitinib, AbbVie) is now approved for the treatment of moderate-to-severe atopic dermatitis (AD) in adults and children 12 years of age and older whose disease did not respond to previous treatment and is not well controlled with other pills or injections, including biologic medicines, or when use of other pills or injections is not recommended. FDA approval of the AD indication for Rinvoq is supported by efficacy and safety data from one of the largest registrational Phase 3 programs for atopic dermatitis with more than 2,500 patients evaluated across three studies. Across the trials, the 15mg and 30mg dosages of upadacitinib met all primary and secondary endpoints at week 16, with significant improvements in EASI scores ans reductions in itch, relative to placebo.

Emma Guttman-Yassky, MD, PhD, Waldman Professor and System Chair of Dermatology at the Icahn School of Medicine at Mount Sinai in New York City was an investigator in the trials. Here she talks about the approval and potential role for Rinvoq in patient care.

What is the significance of the approval of upadacitinib for moderate to severe atopic dermatitis?

Emma Guttman-Yassky, MD, PhD: For many years, treatments for moderate to severe atopic dermatitis were associated with safety concerns. Then came the biologic dupilumab or Dupixent (Sanofi/Regeneron) that really revolutionized the way we treat atopic dermatitis. It is an injection, and, as we know, some adult and adolescent patients do not want an injection. This is why we need to expand the treatment scheme to also include oral medications, and Rinvoq is a very welcome addition, because it fits exactly that bill.

Rinvoq is a treatment that is highly efficacious, works rather rapidly—most of the efficacy is already achieved by week four and within days patients already experienced major improvement, and it is an oral. In my own clinic, I have some patients who prefer an injectable and some patients who prefer an oral medication, and I think we need to satisfy both patient populations.

What stood out to you in terms of response to Rinvoq in the clinical trials for AD?

Dr. Guttman-Yassky: Rinvoq really pushes the bar for efficacy, showing really high efficacy results in terms of both EASI and in the validated IGA that were the primary endpoints. Even beyond that, it reaches very high EASI 90 and even EASI 100 results. Ultimately, our patients want clearance. Rinvoq targets more than one cytokine pathway; it clears more patients and it’s beneficial to clear more patients with different phenotypes of AD.

Itch is the hallmark of atopic dermatitis in both adolescents and adults. It’s the symptom that they complain most about. It interferes with their sleep. I think the data touches upon the quick effect of Rinvoq that, due to its mechanism of action, it really starts to act very quickly on patients. First we see the effect on itch, and then we see also the clearance of lesions.

What do we know about the safety of Rinvoq for AD in the trials to date?

Dr. Guttman-Yassky: So far the safety is quite good in the AD patient population. We need to remember that we are not dealing with the populations treated with tofacitinib, which is a pan-JAK—that is a JAK1, JAK2, JAK3—that was used in the rheumatoid arthritis populations that have more safety issues. You have more cardiovascular comorbidities, but those patients are older. It’s hard to compare our relatively younger AD population to this. So far, in the AD population, it shows good safety.

We need to assess JAK inhibitors over time, and we need long-term data in this population of AD patients. So far, it seems that the AD population shows fewer safety concerns than other populations, such as psoriasis or RA, but for sure we need long-term data, and that long-term data will determine how JAK inhibitors will be used, if they will be used only for treating flares or if they can be used safely on an everyday basis over time.

In the clinical trials, patients were permitted to
use topical corticosteroids as needed. Could you talk a little bit about the reality of what treatment may look like? What is the significance of flexible dosing?

Dr. Guttman-Yassky: In the clinical trial for 16 weeks, it was a monotherapy study. So we are talking about the data that pushed the efficacy ceiling only as monotherapy. Only afterward patients were allowed to use topical steroids in simulating a real-life situation. In real life, this is what happens also with Dupixent. Patients sometimes may still have one or two lesions that they will treat with topical steroids. So this was the intent of the study. Many times, patients did not need to use a topical corticosteroid.

In terms of dosing, we need to start with the lower dose, and only then if patients do not respond, go to the higher dose. But you are not restricted as to how much time you can depend on the lower dose. And each physician will have their own threshold. It will depend on if and when you bring the patient back. I intend to bring the patient back in four weeks and make a determination after four weeks if I want to increase the dosing. I think each physician will be able to decide for themselves when to bring the patient back and decide the dosing.

What’s next for the treatment landscape for atopic dermatitis?

Dr. Guttman-Yassky: It’s exciting to see now two new JAKs—upadacitinib and also abrocitinib—approved for AD, both allowing two doses. I think this will change the lives of multiple adults and also adolescents. I think the future will be to release long-term data from JAK inhibitors so that the community will feel comfortable to prescribe them long-term. It’s very clear that short-term, they will be utilized quite a lot, but we need to understand how well we can use them daily on a very long-term basis. That’s still unknown.