A review of topical JAK inhibitor ruxolitinib.
James Q. Del Rosso, DO: Let’s get into some of the specifics in terms of the therapy. We’ve had a recent FDA approval for ruxolitinib [Jakafi] cream. It was studied in 1.5% and 0.75% in patients with mild to moderate atopic dermatitis. The mean body surface area is about 9% to 10%, which is what we would expect, and the majority were rated at baseline as moderate to severe. Both of those concentrations showed much greater effect in terms of getting patients almost clear and even very rapidly reducing itch, which we see with Janus kinase inhibitors. Getting patients to EASI [Eczema Area and Severity Index]–75 scores is another end point that we look at. But the 1.5% did better pretty much across the board, so that’s the only 1 that became approved. It’s approved in patients who are at least age 12 and not immunocompromised, as the label says, with mild to moderate atopic dermatitis that hasn’t been adequately controlled by other prescription topical treatments. That’s many of the patients we see, and it doesn’t take very long to find that out.
One of the confusions—I’ll ask Neal to comment on this in a moment—is that the labeling carries the box warnings associated with the oral Janus kinase inhibitors, not to mention that some of those adverse effects didn’t happen with the topical. But of the ones we’re most concerned about, many didn’t happen at all, such as malignancies and serious infections. With thrombophlebitis, there were 1 or 2 cases in which that happened, but we don’t know necessarily if they were related to the drug. It’s something we need to be concerned about. But the labeling with the product label, or the package insert, with the ruxolitinib cream doesn’t require that you get baseline laboratory testing and monitor the laboratory tests during treatment, as exists with the oral Janus kinase inhibitors. A lot of people are confused about that, and there are no contraindications. Neal, do you want to expound on that?
Neal Bhatia, MD: Part of the confusion is because nobody is reading the fine print. If you look at the fine print of the black-box warning, it’s talking about the class of JAK inhibitors. There are even mentions of systemic exposures to JAK inhibitors in the fine print of the black-box warning. If you look under the hood of what’s going on with the topical, you don’t want to make the statements that these things don’t apply, but you can read from the inference of what’s going on in the discussion of the true FDA warning, that it’s about the class and not about the single agent. That being said, if you look at the pharmacokinetic data, if you look at the maximum-use data, none will show some major signals that would tell you there should be concerns about absorption unless you have some patients with some difficulty in that regard.
But the advantage, which you touched on, is that we now have a top-to-bottom cream. We can use this on eyelids, around the mouth, on areas that we were afraid of steroid atrophy, especially the intertriginous and popliteal areas where a lot of patients with atopic dermatitis were struggling. The label is the part we really need to discuss: where it fits, and an opportunity to bring down inflammation quickly. And we saw from the NRS [numerical rating scale] data, how quickly the itch-scratch cycle can be broken to give patients some relief. Those are significant parts of the discussion that may not be obvious, and focusing on safety also means focusing on opportunity.
James Q. Del Rosso, DO: It’s getting caught up in the noise. Obviously clinicians don’t want to have something happen where it’s going to snake bite them later. Black-box warnings are something we’ve dealt with for calcineurin inhibitors and many drugs. Probably for a lot that people are prescribing, you don’t realize they have some black-box warnings.
Neal Bhatia, MD: We saw this with oral. I remember when tacrolimus was converted to an ointment. Remember, that was a transplant drug back in the day, and everyone was up in arms about how we were going to use this. Ophthalmologists said the same thing about cyclosporine drops. They said, “How are we going to convert this to safety?” But you look at the PK [pharmacokinetics], the maximum-use studies, and the safety that went along with those, and we have some confidence that we’re going to do right by patients.
James Q. Del Rosso, DO: The bottom line is that the average body surface area was 9% to 10%. This isn’t going to be something you’re putting on patients with 30% to 40% body surface area. You’re going to be putting it on limited, localized areas in patients who are having difficulty with the disease that may be on the milder side, or patients who aren’t responding to other treatments so we want to have a topical therapy. We’re not concerned about where we’re putting it, and we’re not concerned about the adverse effects with topical corticosteroids. All of that’s well said. But I want to move on to the orals, Neal.
Neal Bhatia, MD: Just quickly: there was the 1 study about the comparison to triamcinolone [triamcinolone acetonide]. There have also been comparisons to calcipotriene and some other treatments, showing that we have an opportunity to use it where we were using topical steroids before.
James Q. Del Rosso, DO: Absolutely. The efficacy bears that out, and that study with triamcinolone was done earlier down the line, and you don’t hear people talk about how that’s meaningful in terms of the efficacy of the ruxolitinib [Jakafi] cream.
Transcript edited for clarity.