乌鸦传媒

Upadacitinib was found to be effective over the long-term in adolescents with moderate-to-severe atopic dermatitis (AD).

Investigators analyzed data from three phase 3 randomized clinical trials comprising 542 patients ages 12-17 years through 76 weeks of treatment with upadacitinib. The analysis appears in .

In each of the three trials, the EASI-75 clinical threshold was achieved by 89.1%, 84.4%, and 87.8% of adolescents taking 15 mg of upadacitinib, respectively, and by 96.1%, 93.6%, and 82.7% of adolescents taking 30 mg of upadacitinib across 76 weeks.

Safety findings were consistent with the drug's known adverse event profile (herpetic infection: 4.0, 1.9, and 1.1 events per 100 patient-years, respectively; creatine kinase elevation: 11.6, 11.0, and 7.1 events per 100 patient-years). No new signals were observed in the analyses.

First author Amy Paller, MD, is chair of the department of dermatology at the Northwestern University Feinberg School of Medicine in Illinois. Paller recently discussed the study findings with the Reading Room. The exchange has been edited for length and clarity.

How were you and your team looking to advance the knowledge base around upadacitinib?

Paller: Upadacitinib is a JAK inhibitor, and while there aren't head-to-head trials among every one of these drugs, it really looks like upadacitinib may be at the top of the pack in terms of effectiveness.

But the concern has been safety, and this is particularly true for the pediatric population -- children who would theoretically have to take this medication for long periods to treat their chronic AD. We don't know if there are safety issues. We certainly are concerned about the boxed warning. Any parent of a child, of an adolescent who might be taking upadacitinib will no doubt read about this or be told by the pharmacist and have concerns about some very serious potential risks that have not really been seen to date with this drug in shorter-term trials or in longer-term trials with adults.

So the question becomes: what are the real risks? The more information we have, the greater ability we have to make the difficult decisions about whether it's safe enough to try. This is in general not a first-line agent and probably won't be for a bit for any pediatric patients. The more we can learn about the safety of this drug, the better we'll feel about using it in young patients. Certainly there is even greater concern as we go down in age, but here the focus is on adolescents.

How would you summarize the key findings?

Paller: This investigation extends our knowledge about how well upadacitinib fares in adolescents. We can see that there's good maintenance of control, and at least we don't see any new safety signals. I think that's the simple bottom line.

As a practitioner, I'm continuing to use biologics as first line, but if my first-line agent doesn't work, do I go to another biologic now for those ages 12 and above? Do I go to a JAK inhibitor? How safe do I feel about starting with a JAK inhibitor in somebody who is needle-phobic? Or in somebody who just has seasonal disease but who is going to need medication for a few months every year for years on end? As more data accrue and there are still no safety signals, maybe this [upadacitinib] becomes first line because it is something that is easy to start and stop.

What were the findings specifically around safety?

Paller: We did see that increased risk of herpes -- particularly herpes zoster infections. We do see that increased risk of neutropenia that could make us concerned. We need to be keeping these possibilities in mind. We may not see these very serious problems and that would be great, but we still have to realize that there are also some safety issues that remain that are perhaps more minor, but are still there, particularly compared to biologics.

Do you have any take-away messages for clinicians?

Paller: The biologics are great. They're targeted, they really look safe. But injection is an issue for many people. I think if we don't have oral options, we miss out. So having now several options for our adolescents means the world because they've been transformational in terms of the disease and the quality of life for these patients.