Little head-to-head data exists between JAK inhibitors and biologics, but common metrics of treatment success can help physicians navigate newer agents.
The atopic dermatitis drug pipeline has broadened and accelerated in this last decade to include numerous agents across various systemic pathways being investigated for the chronic disease, if not already marketed. As the research and development of agents across biologics, JAK inhibitor and other drug classes continues, it’s vital for dermatologists to weigh the scales of benefit between one new option and another.
In an interview with HCPLive at the American Academy of Dermatology (AAD) 2023 Annual Meeting in New Orleans this weekend, Aaron Drucker, MD, a dermatologist with the University of Toronto and Women’s College Hospital, reviewed his led session on the comparative efficacy of available systemic therapies for atopic dermatitis.
HCPLive: Regarding the discussion around comparative efficacy for systemic therapies in atopic dermatitis: obviously it feels like it's a luxury in 2023 to have the capability to compare across this spectrum. What exactly did you identify as the drug classes that fit into that, and what were the agents that were highlighted?
Drucker: We are really lucky right now that we have options to choose between when we're thinking about how we want to treat someone who has more severe eczema and needs a systemic treatment. We have biologics, we have JAK inhibitors, and then we have older agents like methotrexate cyclosporine that are still useful. And so, when we're thinking about how to choose between them, not the only thing but one of the things that we need to keep in mind is how effective are they compared to each other?
In our session, we talked a lot about how we can compare them usually using indirect comparisons; network meta-analysis is a technique that we use, because there are very few head-to-head trials. And so using that technique, we're able to get a sense of how these different drugs that have never been compared head to head in a trial compare with each other.
What exactly are our valuations and metrics, especially within adult atopic dermatitis, that are defining efficacy here?
Most people are probably the most familiar with the EASI score, Eczema Area Severity Index. Usually a 75% improvement in that EASI score is going to be the primary outcome of clinical trials; people are used to reading those trials and familiar with those metrics. In our session, we talked about that metric, but also looked at some patient-reported outcomes, things like the POEM, which is a measure of how commonly someone has symptoms of eczema. We looked at quality of life—things that are important to patients beyond just whether their skin is clearing in terms of that EASI score.
I'm glad you mentioned EASI 75. There's been a lot of discussion around the hope that eventually we can move those goalposts to EASI 90 and 100—achieving absolute skin clearance.
Do you anticipate if you were to theoretically lead this very same conversation 5 years from now for some of these biologic agents under development, that that's going to be the more standard approach?
We always want to do better. If we can talk with EASI 90s, that's great. Of course, I would rather my patients have a 90% improvement than a 75% improvement. But I think we're a little bit spoiled from the psoriasis world, where that was how things went. We had our first biologics that were pretty good, better than anything we'd seen to date. And then things just got better from there with more efficacy. And we got used to prescribing them, and it sort of has just become a panacea in psoriasis.
I don't know that's necessarily where we're heading in atopic dermatitis—that would be amazing. But so far, we're not seeing new drugs necessarily be better than old drugs as we're going along. That may change. But I'm not pinning all my hopes on that.
Is there an involvement of the benefit-risk profile discussion in all this as well?
The reason I put together a session that started with comparative efficacy and then went on to talk about safety monitoring and use in special populations...is because really need to take a holistic approach when we're prescribing these medications. Just because something is the most effective doesn't mean that that's necessarily the first-line choice for a given patient, we have to keep in mind safety, both in the short term and in the long term.
And that's going to differ for different patients. A 78-year-old with a lot of comorbidities is different than a 24-year-old who's generally healthy. So, we need to keep all the data in mind that we have for the average person and all these clinical trials and these long-term follow-up studies, but also be very mindful of the individual patient that's sitting in front of us.
What is your advice for prescribing clinicians that are navigating all these new options, and some of the more common questions that they should be anticipating from patients who may be learning about these new drugs?
I think because there are choices now, we need to be having these discussions with patients. You know, the term "shared decision making" gets thrown around a lot, but I really think it's apt here. We need to have discussions with patients—that this is the relative efficacy of these medications, this is what you need to watch out for on this medication in terms of potential safety issues, this medication doesn't have as many safety issues, but maybe as less effective.
These are all the different things that we need to talk about with patients upfront so that they understand what they're getting into and we're not just making a decision for them, because for most prescribing decisions, choosing between a group of 5 different medications, there's not just going to be 1 choice that's right for everyone. And we need to get patients all the information that is going to be useful to them as they make that decision.