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Switching Treatment in AD


Jonathan I Silverberg, MD, PhD, MPH; Elizabeth Swanson, MD; Brad Glick, DO, MPH, FAOCD; and Andrew Blauvelt, MD, MBA, review factors that lead to switching therapies in AD, focusing on monotherapies vs combination therapy.

Jonathan I Silverberg, MD, PhD, MPH: One of the big questions that comes up is, let’s say you go with dupilumab or tralokinumab as a first-line option. How do you make that decision, what comes next? How do you switch?

Elizabeth Swanson, MD: I know, it’s so hard. I tend to stick with the basic approach of asking patients if they’re happy. Is the patient happy, or do they wish they could be doing better? If it’s difficult for them to say that, I say, let’s think back to before starting dupilumab. Where would they rate the severity of their symptoms on a scale of 1 to 10? Then where would they put themselves today? Is that enough improvement, or are they still at a 5 or a 6? By putting it contextually in those numbers, the patient realizes that maybe they could do better. Maybe it is worth it. For those patients who are on the edge, they’re doing OK on dupilumab, but they wonder if they could do better, I’ll often offer a sample of the JAK inhibitor pills. Since there are 2 weeks in a sample, you could give them a couple, and it gives them a chance to see, because of that rapid effect, how they feel on it and if it’s worth making the change.

Brad Glick, DO, MPH, FAOCD: I like the collaborative therapy, and I have a number of patients where we’ve added in an oral JAK. I like the combination of dupilumab and ruxolitinib cream. I think it’s a no brainer because of this new generation of not having to go to the steroid, even if we cycle in corticosteroids. Obviously we have data from the [LIBERTY AD] CHRONOS trial, which is very real world. But now when I have someone who’s happy enough on dupilumab, but yet they’re getting a little breakthrough, rather than shifting, and it could be tralokinumab also, but I’ll get those 5-g samples of ruxolitinib cream and give it to them. Lo and behold, particularly in some areas on the face, sometimes fold, axillary region, antecubital, it knocks it down pretty quickly. So I like the collaboration.

Elizabeth Swanson, MD: I’ll echo that. I love the combo of dupilumab with topical ruxolitinib thrown in. Sometimes insurance can be a bit of a trouble because of the “not to be combined with other therapy” warnings on topical ruxolitinib. I hope one day that goes away or that insurance companies become more able to understand it because I really love that combo.

Jonathan I Silverberg, MD, PhD, MPH: We certainly see a lot of that real-world use. I know we’ve had many conversations also about the idea of monotherapy versus combination therapy. What are your thoughts in this respect?

Andrew Blauvelt, MD, MBA: I think one of the important points that we’ve experienced over the last 6 or 7 years now since dupilumab was approved is that for a long time dupilumab was all we had. So we kept patients on maybe longer than what we do now because that’s all we had, and they were happy mostly. It’s a great start, a great drug. In my experience about 80% of patients do well on dupilumab. These days we’re pushing the envelope. You all are talking about pushing the envelope with additive topicals, and then there’s the other choice, to push the envelope by switching the systemic monotherapy. In my experience, the patients coming in for trials are done with topicals. They’ve been so topical heavy in their lifetime, all day they’ve been putting stuff on their skin. So, I like the idea of spot therapy, but on the other hand, if you think about the ease and what the patients want, it is to do the least possible to be healthier and normal. We now have tools that can take us farther away from topicals for those tough patients. Of course, spot therapy, I’m a fan of that too, but I’m trying to put myself in their shoes and, “I’m doing this shot, but now you want me to do a cream too.” It can get old after a while, I think.

Jonathan I Silverberg, MD, PhD, MPH: That comes full circle to what we talked about, the shared decision-making. Shared decision-making is not just how to decide the first-line therapy, but if you’re not getting the best response with whatever drug, where do we go next? Do you try combo therapy? Do you switch class? Do you switch within class? The truth is they probably all will work in some patients, and I wish we had better studies that could inform that or give us personalized medicine approaches, but until we have that, we’re going to be doing this trial-and-error process.

Andrew Blauvelt, MD, MBA: There was an interesting psoriasis study of patients who had failed, and they defined that as failure of an IL-17 [interleukin-17] blocker, and then treated with an IL-23 blocker. We’ve had prior use of biologics and then a new one, but true failure with a definition, and then going on, so a tougher crowd. We maybe need that study in atopic dermatitis. A true failure, and then when you switch, and in the results, there was improvement in the bottom line. The definition of a failure of an IL-17 ended up being a tough patient because the results were not as good as a patient off the street being treated with an IL-23 blocker. Do you think the same thing would happen with such a trial?

Jonathan I Silverberg, MD, PhD, MPH: I think it’s a really hard study to do. I’m not sure anyone wants to jump into that unless they’re absolutely forced to. I suspect that won’t become a standard in the trial space for a few more years at least. Just clinically, I’ve cycled through all these different medications. You get patients who do better with dupilumab than tralokinumab, better with tralokinumab than dupilumab. So, we can look at trial data to predict a population response, but when you’ve that one patient in front of you, you don’t know what’s going to happen. You have to go with it and see where it goes.

Andrew Blauvelt, MD, MBA: I like the idea that they won’t necessarily fail the next one because they failed the first one. That’s an important message.

Transcript edited for clarity

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