Topical JAK Inhibitor Reduces Itch in Patients With Atopic Dermatitis

Shawn Kwatra, MD, FAAD, director, Johns Hopkins Itch Center, shares findings from a recent analysis of two phase 3 trials which investigated the efficacy and safety of a Janus kinase inhibitor for patients with moderate to severe atopic dermatitis. 

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I'm Shawn Kwatra, director of the Johns Hopkins Itch Center here in Baltimore, Maryland. It's a pleasure to speak with you today.

What inspired this analysis of the TRuE-AD1 and TRuE-AD2 trials?

Chronic itch is a terrible problem. It is, in some cultures, actually a form of torture. And it's received very little attention compared to chronic pain.

Atopic dermatitis is one of our most characteristic itch disorders, and itch is the cardinal symptom that mediates reduction in quality life. We wanted to see the function of a novel, recently FDA-approved therapy, topical ruxolitinib cream, on pruritus and itch.

One of the most important things to consider is how quickly itch is reduced, and the extent of the itch reduction is as well. Those are all important factors because when we're counseling patients, that's arguably the most important thing that patients want to know—how quickly is the itch being improved?

Can you walk through your methods and key findings? Did any of the results surprise you?

Sure. These are two large phase 3 trials, TRuE-AD1 and 2, with multisite data that was analyzed. Data was analyzed based on itch improvement, and itch improvement was assessed at multiple time points.

One of the really cool aspects of the study is we were able to get a sense for how quick the itch improved. What we found is that itch improvement occurred rapidly, in some cases even within 12 hours. What's also very interesting is that the itch improved dramatically in many patients.

One of the analogies I'll give you is, in psoriasis, we've had many agents approved over time and the bar keeps getting higher. Originally it was PASI-50 or -75, then it was PASI-90, and now it's PASI-100 in some situations, in terms of improvement in psoriasis. Similarly, this is where we're going with itch.

The FDA mandates a 4-point reduction in itch. That's one of the very important key metrics for approval. I would contend if you have an itch of 10 or 7 and you go down to a 6, 5, or 4, that's not really where we want to be. We want to be in mostly an itch-free state. In this trial, a greater portion of patients were able to achieve an itch-free state. That's itch of either 0 or 1 in the preceding 24-hour period compared to placebo. This happened very quickly in these patients, within just a few hours after administration, and it was preserved throughout therapy.

That's very important for us to show not only is there a rapid improvement in itch, but that it's very significant clinically, and most of these patients are having a nearly complete resolution of their itch which is maintained over time. That was the impetus for the study and also the results that confirmed it, which are very important at the bedside.

What are the real-world applications of these findings for patients with atopic dermatitis?

There are going to be a lot of options for patients with atopic dermatitis. This is a revolutionary time.

With systemic options, we started with our first injectable in the 2000s, and a few years ago 2017. We've had a flurry of approvals including oral JAK inhibitors and monoclonal antibodies that are approved or awaiting approval.

Topically, we've been reliant on nonspecific therapies that are riddled with either a lack of efficacy or side effects. The side effects of topical steroids are hypopigmentation, atrophy, all of those things. Topical ruxolitinib represents a novel therapeutic option for patients with atopic dermatitis that is rapid in its itch relief.

In the phase 2 study, we saw it was even more potent than triamcinolone, which is one of our standard mid-potency topical steroids usually given to patients. I think many patients are going to be interested in this, especially patients with skin of color who may be more prone to hypopigmentation. I think there's a big hunger among all patients to try to have less of a reliance on nonspecific therapies. This is a great step forward, I think, in the management of atopic dermatitis, to have a rapidly acting antipruritic option, which is the number one concern among patients.

Is there anything else you would like to add?

I'm very proud of this study because I think it's very bold to go toward itch-free states, because that's what patients want. Patients don't necessarily want a 4-point reduction in their itch. If you look at all the spinoff studies that have been performed from large phase 3 clinical trials, they're focusing on a 4-point reduction. But that's simply inadequate for patients and for us.

Many patients have very severe itch, and going from a 10 to a 5, a 10 to a 6, or a 9 to a 5 is not enough. We need to be seeing more of this itch-free state, with 0 to 1. That is what will resonate with both providers and patients. That's why I'm really excited about it.

I think this also heralds a new step forward in terms of additional studies and analysis of data to get metrics that are important to clinical care, which is what this is.