How Payers Can Use Clinical, Value Comparison Data for Atopic Dermatitis Therapy

Gary Owens, MD, president of Gary Owens Associates, shares his thoughts on the challenges of choosing treatment options for patients with atopic dermatitis, and highlights key takeaways for payers from a recent ICER report which compared the clinical effectiveness and value of JAK inhibitors and monoclonal antibody therapies.

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Welcome back to PopHealth Perspectives, a conversation with the Population Health Learning Network where we combine expert commentary and exclusive insight into key issues in population health management and more.

Today, we are joined by Dr Gary Owens, president of Gary Owens Associates, who shares his thoughts on the challenges of choosing treatment options for patients with atopic dermatitis and highlights key takeaways from a recent ICER report which compared the clinical effectiveness and value of JAK inhibitors and monoclonal antibody therapies. Gary?

Hello. I'm Gary Owens. I'm a physician with about 25 years of expertise in the managed care world as a former VP of Medical and Pharmacy Management at a large Blue Cross plan in Philadelphia. I have, for the last decade or so, been in the consulting world as president of Gary Owens Associates, where I provide consulting input to a number of developers of new technologies.

When there are multiple approved drugs for something like atopic dermatitis, what factors are most important in choosing a therapy?

Thanks, Edan. This is certainly, as you know, a very dynamic field right now. If you look back in history, prior to the launch of dupilumab, atopic dermatitis really wasn’t something that was even a major issue for payers.

It was mostly treated with topical therapies, moisturizers, corticosteroids, topical calcineurin inhibitors. For the more severe patients, some of them were receiving off-label treatment with immunosuppressants. It wasn't an area of focus or management.

Fast-forward to the launch of dupilumab for the treatment of adult patients with atopic dermatitis. Suddenly, we had a biologic introduced. It was, at that time, the only biologic. Subsequent to that, the data has allowed the treatment of younger individuals, down to age six now, I believe, with atopic dermatitis.

Of course, dupilumab has also gained additional approvals in other indications, like asthma and chronic rhinosinusitis. Suddenly, the area has become an area of focus for payers.

Today's conversation is somewhat apt. You may have seen that just yesterday, ruxolitinib topical was approved for the treatment of atopic dermatitis, not the moderate-to-severe but more the mild-to-moderate patients. It introduces yet another moving part.

Then, of course, on the horizon, there are a number of oral JAK inhibitors, back in 2020, that submitted to the FDA for approval, those being baricitinib, upadacitinib, and abrocitinib. Then, of course, there's an anti-IL-13 that also submitted to the FDA in 2020, tralokinumab, which is still in the works as well, although it did receive a complete response letter about some manufacturing issues.

What I'm saying here is we have an increasingly complex area where historically we've had one biologic. Now, we're going to have potentially another biologic and three JAK inhibitors coming to the field.

It's going to create, certainly, some payer and provider issues about who's the appropriate patient for which agent, should there be a preferred agent in this class, should there be multiple preferred agents because of different mechanisms of action, and all that in the context of an area that's rapidly increasing in cost.

Great, thank you. My next question is, what is uniquely challenging about caring for this patient population?

There's a lot of unique clinical challenges. First of all, this disease can affect people of all ages. It often presents in infancy. Many of the children with atopic dermatitis do spontaneously resolve as they move into older childhood and adolescence. Literally, this is a disease that can affect any age from infancy up through older adults.

It's also a very wide spectrum of clinical presentations. You have the eczema or mild-to-moderate disease that can often be controlled with local therapies. Sometimes even just simple things like moisturizers are adequate treatment for the mildest cases, or skin barrier protection.

Then you move on to some patients needing intermittent topical corticosteroids or calcineurin inhibitors and others who need almost constant treatment with topicals. Of course, as more body surface area becomes involved in some of these patients, it becomes very difficult to manage topical therapies. Imagine putting topicals on 20% or 30% of your body.

Then, of course, there are always the moderate-to-severe patients who are not well-controlled on these agents. Then their options include off-label treatments with immunosuppressants or maybe phototherapy. Then, of course, the moderate-to-severe patients who are candidates for dupilumab.

Why this is challenging is because, first of all, the society guidelines are a bit out of date. Providers as well as payers don't have a good set of updated guidelines to work with.

Second of all, there's no real good, constant definition of when one transitions from mild to moderate, from moderate to severe. You can use things like percent body surface area involved. You can use things like the global assessment tools. You can use things like itch scoring tools, but, again, there's no bright dividing lines that you can use to see when these patients are moving up the scale of severity.

All that creates some challenges for payers to know when it's appropriate for these patients to be covered for either biologics or, in the future, other therapies. It creates challenges for clinicians, as to when these patients become candidates for advancing therapy. Those are some of the biggest challenges we see out there.

The Institute for Clinical and Economic Review recently released its final policy recommendations for JAK inhibitors and monoclonal antibodies for the treatment of atopic dermatitis. What should payers' main takeaway from this clinical and value comparison be?

There are several main takeaways, many of which were outlined in the report. The first one of takeaways is that it is a dynamic field, as I've already pointed out. The introduction of potentially three oral JAK inhibitors is going to make the management of this area more complex.

As you saw in the ICER report, there's relatively incomplete data. Yes, we have some data from the JADE COMPARE trial that abrocitinib may improve pruritus faster than dupilumab. We have some data from the Heads Up trial that upadacitinib may be superior in reaching an EASI-75 score over a 16-week period, but those are relatively short-term trials.

We don't have long-term data to compare even those two versus dupilumab. We have no comparative data across the unapproved JAK inhibitors, simply because there's no way to do that under current FDA guidance. Then, of course, tralokinumab, there's no comparative data there.

If it's going to create some issues for payers about which therapies are going to be most appropriate. One of the things payers will rely on is experience. There's a vast clinical as well as payer experience with dupilumab.

Most payers do have dupilumab on their formularies, typically in a specialty tier with some level of prior authorization, although my understanding in talking to my payer colleagues is the prior authorization requirements have modified themselves over the years that dupilumab has been available.

Most payers require at least topical therapies to have been tried and failed. After that, if the patient is an appropriate candidate and has moderate-to-severe disease, it usually gets approved.

Of course, the other issue, the takeaway, is there's a wide variation in cost of these agents, with upadacitinib, at least with a WAC price, significantly higher than, say, dupilumab or something like baricitinib. Of course, we don't have prices for abrocitinib and tralokinumab because they're not on the market for other indications.

Most importantly, especially for dupilumab, which is unusual in ICER reports, it was deemed to be relatively cost-effective at its current price, with a recommendation that the discount from WAC would be negligible to reach a cost per QALY at a $150,000 threshold. It would be about a 6% decrease.

In a world where, in cancer drugs, we're often used to seeing 200% or 300% plus decreases needed to be cost-effective, this is a bit of a breath of fresh air for payers, that the drugs that we're paying for are relatively cost-effective.

For upadacitinib, the price there seemed to be less cost-effective and would have to come down a good bit more. In comparison, they said somewhere between 35% and 53%.

Where does that leave payers? It leaves payers with being relatively comfortable with their current approach to managing dupilumab and finding that it's relatively cost-effective in its current state. Where it doesn't leave payers is: "How am I going to manage my formulary when I have potentially five agents with relative lack of comparative data?"

ICER recommended that an ideal formulary would have an agent in at least each class. You'd have an anti-IL-4/13, an anti-IL-13, and a JAK inhibitor. I suspect a lot of payers are going to look in that direction as to how to approach this class.

Even then, it's going to get more complicated. Where, for instance, do other topicals fit in the cascade? Ruxolitinib is adding a wild card for which we have no experience. Will some payers want to see a trial of ruxo in some of these patients before they move on to biologics or JAK inhibitors?

Then, of course, even further down the road, in a couple of years, we may have even more agents, such as lebrikizumab, nemolizumab, and even delgocitinib, for instance. Then, of course, JAK inhibitors may look to get extension of their indications down to younger age groups.

Finally, for the JAK inhibitors, all that gets complicated by the cardiovascular safety warnings and how are payers going to need to treat that in their assessment versus dupilumab, which doesn't have those safety warnings and, over time, has proven to be a very safe drug for most patients.

We're going to see a lot of challenges at P&T committees, a lot of discussions, a lot of need for our dermatology experts to weigh in on this, especially around the area of safety in the JAK inhibitors. As we know, dermatologists are relatively risk-averse in a lot of their treatments and may approach the use of JAK inhibitors very carefully.

I don't have firm answers as to how to manage this class, but I do think that many of the recommendations in the ICER report, such as perhaps having more than one preferred agent in maybe more than one class, as having minimal step requirements for those moderate-to-severe patients, typically through a reasonable course of topical therapy with calcineurin inhibitors and/or topical corticosteroids, and maybe even a course of crisaborole, which we haven't mentioned as yet another agent—I think those recommendations are reasonable.

Then, of course, the recommendations on the manufacturers. This is a fairly common dermatologic condition as compared to some of the more rare conditions, so manufacturers need to be responsible in their pricing.

We might even use the example of upadacitinib, which was priced for RA. Does there need to be a different price for atopic dermatitis? Which leads us to a discussion I'm not going to get into because it's beyond the scope, but are indication-based pricing for some of these agents on the horizon? That would be the topic of yet a whole webinar, even, if I were looking at this.

Thank you, Gary. That's the majority of my questions. Is there anything that I haven't asked you about or anything that you'd like to add?

The one thing I'd like to add is this area is going to be continually evolving. It's going to have more and more new agents. Payers are going to need to put this area of treating atopic dermatitis front and center.

For instance, it's probably likely, within the next year or so, that dupilumab is going to get that six months to six year indication. Now, we're going to have a pediatric population that's younger and younger to deal with in biologics. How do you manage that?

My advice to payers is stay up to date on this. Keep your eyes on the pipeline and FDA approvals. It's going to be a bit like cancer, isn't it? It's a new event every week. In this area, it's maybe not going to be weekly, but certainly, there are going to be very few quarters in the next two or three years that go by, that you won't have to bring this issue up before your P&T committee.

Thank you so much for taking the time to speak to me today. I really appreciate it.

It's my pleasure, Edan. Hopefully, this has been helpful to our payer audience. As always, it's my pleasure to chat with you and my colleagues virtually out there. Have a great day.

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