Transcript
Brad Glick: I wanted to also ask what beyond the hives and the itch, those two most critical assessments that we make diagnostically in the clinic that lead us to just jumping in, as you said, Laura, with the therapeutics that we have in the toolbox.
But what other questions, what other prompts for our colleagues, take us a little bit further down the road of not only diagnosing CSU, but perhaps even as it relates to access to some of the newer therapeutics in terms of documenting, and I'm thinking more like the burden of disease. What other questions do we ask, or what are patients feeling or seeing or what they're dealing with in terms of their CSU?
Larry Green: Everything we already mentioned is what I would say. You talk about the burning, inability to sleep, things like that. Failure of antihistamines, second-generation antihistamines, the non-sedating ones. Things like that are what I look for before you want to try and gain access to medicines like remibrutinib or dupilumab. That way you want to document and it makes it easier, I think, to access.
Brad Glick: Yeah, I think the sleeplessness is also important, too. We talk about that a lot with atopic dermatitis. I don't think this is too dissimilar. And of course you can't sleep at night because you're scratching because you have hives, even if it's within 24 hours and unpredictable as CSU may be, that's going to really impact your quality of life and maybe even impair your ability to work or even if you're at work to be able to stay at work and what have you. So I think that's really challenging for our patients.
Laura Ferris: I think that unpredictability is also really something that my patients have struggled with, that I can just think back to one of my patients and she was going on a trip, like a big vacation, and she was so scared that she was going to have a terrible flare and it was going to ruin this trip, or she'd be going into something important for work and she would get hundreds of urticaria, they'd be on her face, they'd be on her arm. And you can't predict that, you can't prevent it. I think that that is just so life-altering for patients.
Brad Glick: It makes me think about another discussion point, which is just antihistamines in general. What are your experiences with using antihistamines? At what point do you dose escalate? And let's talk about timeframes, too. I know there's recent guidelines for this and European guidelines really just published in March of this year, but what are your approaches, both of you, in terms of when you have someone who has CSU, they come to the clinic, you're going to probably put them on a second-generation antihistamine. I lately, just me personally, starting actually with double dosing, I don't even necessarily start with one because I find that most of the time it doesn't work if I have the proper diagnosis. What do the both of you do, Larry? Start with you first.
Lawrence Green: Well, I guess I do start with double dosing. I start with regular dosing BID is where I start, and then I'll dose escalate from there and double that. But I don't do that right away. You have to give them a few weeks to see how they respond. It's something you don't want to wait three days to see how they respond. I mean, they'll know, but I want to give it at least two weeks is what I would say. And then I would double the dose BID, and if that's not working, you can go higher on antihistamines, but I'm going to start thinking about remibrutinib and dupilumab and omalizumab. I don't know what you were doing.
Laura Ferris: Yeah, I start people on BID dosing of whatever their favorite or my favorite of the week, non-sedating antihistamine or second-generation antihistamine is. I tell them that if they are... Well, one, I also tell them this is not a PRN drug. This is a drug that you take every day...
Brad Glick: So important. So important.
Laura Ferris: ... oh, take it if you flare. I tell them, "We're preventing flares. So even if you have no hives, you got to take it twice a day. If it doesn't prevent it within a week, I say the next thing we're going to do is go to four a day, so just go ahead and put yourself up to four a day." I also have to tell them it is safe to be on four a day even if it's inconvenient and that we need them, one, because if it works, it's great. And two, we're going to need that to get you on the next step of therapy.
Brad Glick: I was so hopeful that that was going to come out in this discussion too, because it makes me sound like I'm a broken record with my patients because I tell them all the time, "This is a commitment to staying this on every day. There's no drug holiday here because you have to suppress the hives." And we get this all the time that, "Well, I take it for a few days and I stop. I thought it was pretty good," and they have to take it. I love that with the dose escalation. Larry-
Lawrence Green: That's so important because patients often think that the antihistamines don't work if they take it after the fact. There's no after the fact in this condition. Even in urticaria, forget about chronic urticaria. After the fact is not the way to do it. You have to take it all the time as prevention, and that's the way, very important to stress that because after the fact it's not going to help.
Brad Glick: So we have three agents that are FDA approved in the toolbox right now. One we've had for a very long period of time, one that is fairly recently approved in the last couple of years in dupilumab, and then most recently our Bruton kinase inhibitor in remibrutinib. Tell me your thoughts about what those three therapies have done. Let's start more or less with the two injectables, which we've had more recently. And I personally think that omalizumab has made a little bit more of a comeback because of what we talked about before, which is it's a little bit easier to be able to use. Our monitoring concerns are certainly less. But what about those two therapeutics? They're both injectables, your thoughts about those agents, and then something new coming into the toolbox?
Laura Ferris: Yeah, so I think omalizumab is a great drug. I wish that we could give it in dermatology in my office, but in other places I've worked, we have been able to do it. It can really make a huge difference for patients. It can be effective in the long-term. It's also important to tell them they want immediate relief, and so I really need to tell them, "You're not going to walk out of here and tomorrow be hive-free. We want to see where you are in two to three months to judge how this is working. We may need to up your dose. We may need to go to every two weeks." So, I generally start at the highest dose, but I think it's a great option for us to have. Dupilumab, on the other hand, is nice because it's something we're so familiar with. Also not the most rapid drug, but something that it's so, already been in our dermatology toolbox. It's something that we all use all of the time. Very well-known, good safety profile. But, again, not going to be the fastest drug in most cases.
Brad Glick: Yeah, I think those are such great points. Larry, anything to add in your experience?
Lawrence Green: I would just add that I'm really much more comfortable with dupilumab because I've been using it for so long, as well as remibrutinib because it's an oral option for my patients. Omalizumab is a great choice, but as someone in private practice, and it came out on its own, and I had little experience with it because I was worried about the monitoring. I don't have to worry. I mean, dupilumab is like a no-brainer. Who's not been using it for 15 years? And remibrutinib is an oral product with no monitoring. I mean, again, very easy for me.
Brad Glick: Choices. I mean, it's as simple as that. And if you think about it, other than omalizumab, which we've had for a long time, I think it kind of fell off of our radar, maybe was a little bit more in that allergy world, part of this discussion that we're having today. Now, I think the patient that really doesn't want to do the shot really has a new choice. And one of the things that we didn't talk about is speed, and I think that you can tell patients that we know from the REMIX-1 and REMIX-2 trials, those landmark double-blind placebo controlled trials that led to the approval of remibrutinib, those patients were getting better within the first two weeks. And now there's some data to suggest that actually within the first 24 to 48 hours, patients saw their itch improved most significantly, even with some reduction in their hives.
And personally, for me having used the therapy, I've actually seen that happen. So from a practical standpoint, I tell patients just so, what do we like to say? Under promise, over deliver. So we'll tell them that in the first couple weeks you're going to get better, but I agree completely that with the two injectable therapies, surprisingly so, there's kind of a buildup to maybe saturate the receptors. And I find with remi, it works a little bit faster.
Lawrence Green: And like I sort of mentioned before that an oral option, patients seem to prefer oral options a lot. It's just easier for them. It's more comfortable for them. There's injections, maybe if it's one injection every year, patients will accept that. But if it's one injection every few weeks, it's a different story and patients seem to prefer oral options. So it's something you want to talk to your patient, individualized decision for sure with the patients what they want to do, but bring that up. They like the oral option.