Chronic Urticaria: Antihistamines, Biologics, and BTK Inhibitors (Recording)

This webinar was recorded on April 16, 2026

Chronic urticaria is a complex and often persistent condition that presents ongoing management challenges for clinicians. Optimal care frequently requires a stepwise therapeutic approach, careful monitoring of treatment response, and familiarity with emerging therapies as the treatment landscape continues to evolve.

In this live webinar, Dr. Clinton Dunn will provide an evidence-based overview of chronic urticaria management for clinicians and other medical professionals. Topics will include the effective use and optimization of antihistamines, clinical scenarios in which escalation to biologic therapy should be considered, and the latest data on Bruton’s tyrosine kinase (BTK) inhibitors.

Speaker:
Clinton Dunn, MD

Clinton Dunn, MD, is a board-certified physician in pediatrics as well as allergy and immunology, practicing in the Norfolk and Hampton Roads area. He is affiliated with Children’s Specialty Group, which is part of Children’s Hospital of the King’s Daughters, and he is an assistant professor at Mason and Joan Brock Virginia Health Sciences Center at Old Dominion University. His clinical interests include allergic skin disease, asthma, pediatric anaphylaxis, inborn errors of immunity, and primary immune regulatory disorders. Dr. Dunn is involved in teaching medical students and residents, emphasizing evidence-based, cost-effective care.

This Advances webinar is in partnership with the American College of Allergy, Asthma & Immunology. ACAAI offers CMEs for physicians for this webinar. If you are a member of ACAAI, you can obtain CME through the member portal for the Advances webinars.

All attendees will be offered a certificate of attendance. No other continuing education credit is provided.

Sponsored by the American College of Allergy, Asthma and Immunology

Transcript: While this transcript is believed to be accurate, errors sometimes occur. It remains your responsibility to evaluate the accuracy and completeness of the information in this transcript. This transcript is not intended to substitute for professional medical advice.

Feel free to let us know where you are joining from, whether you are a clinician or caregiver. We like to know that. I will go ahead and get started I’m really marker. I’m the education program manager at the allergy and asthma network. I’m delighted to welcome you to this afternoon’s CME accredited webinar. We have a special presentation today focused on antihistamines, Biologics and BTK inhibitor’s. Before we get started, I will go over a couple housekeeping details. Everyone will remain on mute during the webinar to minimize any distractions. We will record the session today in its entirety, and uploaded to our website in a few days. You can watch all of our previous recordings on our website, at allergyasthmanetwork.org and look at the free webinars. Our webinar schedule today is scheduled to last one hour. That will include time for questions and answers after the presentation. You can send any questions throughout the presentation in our Q&A box open — located at the bottom of your screen. We also have a team member that will be checking the chat if you have any questions or need technical support or help. We will try to answer all the questions before we finish today’s webinar. This webinar is brought to you in collaboration with the American College of allergy asthma and immunology. The college offers CME credits for physicians and attendance credits for all others. You can create a free ACA account and earn CME credits for this webinar through their member portal. All attendees will receive a certificate of attendance. Please note no additional continuing education credits will be provided. A few days after the webinar, you will receive an email from Zoom with supplemental resources related to today’s webinar, as well as a link to download that certificate of attendance. Please feel free to drop any concerns you have in the chat. Today’s presentation is titled chronic urticaria, into histamines, Biologics and BTK inhibitor’s. It remains a complex condition that requires an individualized approach to treatment, along with staying current on emerging therapies. Into his webinar, we will explore practical strategies to improve symptom control and enhance patient outcomes. Joining us is Dr. Clinton Dunn, a full-time allergy and immunology clinician, serving the Norfolk and Hampton Roads area as part of the children’s specialty group affiliated with Children’s Hospital of the Kings daughters. He is also an assistant professor with Mason and Joan rock Virginia health science at Old Dominion University. Dr. Dunn has clinical interest in allergy skin disease, asthma, pediatric, anaphylactic’s, and primary immunity regulatory disorders. He is also actively involved in teaching medical students and residents with an emphasis on evidence-based cost-effective care. With that, I will hand it over to you, Dr. Dunn. Thank you for being here with us today.

Dr. Dunn: Thank you for having me. We are going to get started. I’m going to keep this pertinent to families or individuals that are suffering with urticaria as well as providers so we can try to walk through all of this. Neither myself nor Ruthie or our support staff has disclosures related to everything. Our objectives today is that we will try to learn about urticaria, subtypes, and applying what we know about urticaria to help make better life, quality of life emphasis for families and for patients to set us up for success. I always want to start with the basics. Whenever I’m working with any training, I start with what are the basics of everything. With urticaria, we always start with our nomenclature about timing. We have acute versus chronic urticaria. Acute urticaria is something that lasts less than six weeks.

Chronic is greater than six weeks. That is continuous six weeks, not intermittent, it is most days of the week during those times. I apologize when I use the term wheel, we are talking about an area in the epidermis where there is swelling and where they have the classic description of wheal angioedema. Deeper swelling is underneath the epidermis. Typically there is more in related to the urticaria, whereas the angioedema has more tightness in tingling aspect rather than anything else we are focusing today for urticaria and angioedema on histamine driven symptoms. There is another ideology for urticaria that is driven through a separate process that I’m not quick to be adequately able to cover. I’m mainly going to be talking about crowded — about chronic urticaria. It is the big umbrella term. When we talk about chronic urticaria, there are subtypes, and we will talk about what are called endo-tights and a second. The subtypes for chronic urticaria, we really break them down into chronic spontaneous urticaria, sometimes called CSU. If you see me talk about CSU, it is chronic spontaneous which means it comes out of nowhere, or does not really have a preceding exposure that we think about. Then chronic inducible urticaria is a different subtype. Spontaneous comes out of nowhere with no provoking, whereas inducible, we do something to provoke it. That could be because of dramatic raffia, stretching of the skin, pressure, heat, temperature, sun, water, or even our internal core body temperature. There was a really good review that I will always point back to whenever we think about it. The thing on the left comes from our updated urticaria international guidelines. About a year ago, there was a big paper that looked at the subtypes of cold induced urticaria. For so long, clinicians called it cold induced urticaria. Cold induced urticaria can have a lot of different modifiers or cofactors where you can have overlap, cold induced, so there is more overlap in the chronic inducible urticaria. Most of our therapies are focused on chronic spontaneous urticaria. Every time we talk about the disease, we need to think about the epidemiology of the disease. Chronic spontaneous urticaria affects around 1% of the population.

It is estimated there are three known individuals inside the U.S. that have chronic spontaneous urticaria which is a large amount. CSU is predominantly female, older, and most patients with CSU are really bothered and have symptoms that last for a long time, with about one in five having symptoms more than five years. It really can be a huge burden that we have to think about. Whereas with inducible urticaria, there is overlap with people who have inducible urticaria also having spontaneous. They tend to be younger, tend to be our adolescents or young kids. But they are more symptomatic for longer durations. They tend to be people that will have episodes where they will go into remission, but it will relapse and it will last much longer in their lifetime. Why the lecture? Ruthie kind of hinted about it. Urticaria is one of the most bothersome allergic skin conditions, even skin conditions in general. Our colleagues with a talk about the dermatology life quality index. Which is a marker for how much our life is impacted outside of just clinical visits. Looking at sleep, daily function, ability to socialize, go to work, absenteeism. Our internal self perception. We do know that chronic urticaria has a higher impact on quality of life than psoriasis. It correlates really highly with mental health disorders including depression and anxiety and people who don’t feel hurt or appreciated. They have to remove themselves from a lot of their life, what they enjoy to do. That correlates nicely with elevations in our urticaria activities. We will talk about what the activity score is later. But people who have higher urticaria activity score tend to utilize health care, have more hospital visits, doctors visits, require more medications. This is a population we could intervene on and help with. An tracking using standardized questionnaires can set us up to make sure we are identifying and treating them appropriately on who needs systemic therapies. And it can be cost effective. One of the biggest changes in the last couple of years is something that came out about endo-tights of chronic spontaneous urticaria. We have known about asthma.

For those of us who are not clinicians, the concept behind endo-types, there is an underlying mechanism that drives the process we see externally. We have done a good job of defining endo-types. And we have realized two manger endotypes we have started — two major endotypes we have started to see, type one and type 2b. It is called auto allergy, type one, where you are making allergy antibody that attacks are normal tissue like thyroid tissue or other presentations that we naturally see in the proteins that circulate. It activates our allergy cells because we make those into bodies instead of anything else. Type 2b is when we make an IGG that attacks our allergy cells. That is actually IGG directed to our — which activates mass cells through that signaling of IgG. Which is important because we focused our therapies mainly on that direct pathophysiology looking at mass cells. When we talk about it, and helps explain why some patients respond to certain medications. But I will point out whenever we start to talk about endotypes, we realized it is non-type of cohort. There was a lot of overlap between the type one and type 2b where 89% of patients with type two — type2b also had type one. Our nonresponders also have nontype a bull endotypes. We still have a lot of work to go. One of the biggest things we always said was routine labs are not cost-effective, and they did not change the clinical outcomes. This is going to be changing based off of what our new therapies are. I do think it will help guide us with everything. Most important thing we can think about when we talk about chronic spontaneous urticaria is the history and physical we get. Every visit with chronic urticaria, whenever I see a patient in my clinic, I’m always thinking through the c’s. Many times, people come in with a diagnosis of chronic urticaria, and what they are describing may not be urticaria. We have and live in an age where we have enough technology, we can get pictures and have patience bring in an. I encourage all of my patients to take as many pictures so I can see what they are struggling with to help set them up for success.

Looking at other causes as far as trick to make sure that we do fit them into an endotype box but also determining cofactors, so the inducible urticaria’s and comorbidities, including assessing mental health, which I acknowledge in a busy allergy clinic, I struggle with how we need to grapple with the mental health applications on our patients with chronic urticaria. I think it is important to always circle back every single time to what is the activity, how much is it impacting and how we can try help control them. Either escalating up or de-escalating when those choices are available. For all of our trainees out there, I do think we need to make sure we put an emphasis on the differential for chronic urticaria. Even though we will say this patient has urticaria, sometimes we don’t revisit those patients and say, is that still correct? Going back to confirming the diagnosis every time, I harp on the red flag symptom. Whenever I’m confirming, not just looking at pictures but making sure we are not missing something underlying. Especially making sure we are not having it in one location for greater than 24 hours, that are not leaving marks, that we don’t have skin changes or scarring or have a systemic cyst — symptoms. At last, night sweats, fevers. We need to make sure we are not missing other things. The differential is on the left, looking at our syndromes, Glace syndrome, associated with angioedema. Making sure if we have urticaria with angioedema, that is a different process than just angioedema alone. If we have more chronic changes, do we need to get skin biopsies, are we having a string or peeling? Making sure we are not missing something while we try to treat them. I have been more successful when they keep that Brad and thought, even — that broadened thought, they just make sure we don’t miss anything the most recent guidelines that came out about two months ago did start to put more of an emphasis on the. For the first time, we are starting to see recommendation for us to get complete blood counts, to get anti-thyroid peroxidase testing and total ID. Now there is some recommendation that at least on the initial question that those may be utilized, there is mention, those are a little more debated. Those are usually guided more by history, where we actually try to think about it. For the inducible urticaria, we talk about the specialized testing and I would work with a board-certified allergist to make sure we are appropriately doing testing indicated in that situation. We want to make sure if they have inducible urticaria, we see how they are provoked and how they can mitigate those cofactors. The whole point of this talk was to focus on the antihistamines, the Biologics, and that BTK inhibitor’s. I’m go to transition from understanding the background of what we know to do from a basic standpoint to saying, let’s dive in and start to treat this.

Our guidelines have been doing a good job of being updated. After patients therapies, we are in an exciting time where we have systemic therapies. We had to use immunosuppression, and I’ve used those in my career. I do think there is a utility to them. I think now we have a lot of better, safer options that we can talk through. Our guidelines do mention three systemic therapies that we will dive in on. First, we need to make sure we talk about antihistamines. By the time they come to see me in allergy clinic, the thing about antihistamines as we treat the symptoms they have. Most people start standard dosing, which is the packaged label recommendation. We tend to prefer second-generation antihistamines. Outside the U.S., they have by lasting and repetitive. Whenever we start therapy, we start the lowest dose to try to make sure we don’t over medicate and we try not to make sure that we run into side effects. For the longest time, I will show you about the literature about how many patients respond to antihistamines, we try to find the most minimal amount of medicines we want to use. If we do have unresponsive patients, you can up the dose and the guidelines talk about that therapy. By the time they are seen in the allergy clinic, we have already have them on that. It can increase the dose for skin conditions up to four times per dose. We should be monitoring for side effects. Most common side effects in different populations will be sedation, or other side effects that we see often. There is literature on adding other histamine blockades or others. More evidence for the leukotriene receptor. I will give little plugs along the way for some good resources.

There was a paper out of South America that looked at prognostic calculator, to say, just my patients will be the ones that respond to antihistamines? It was different in each culture but it did set them up to help the clinicians predict it. I don’t know if the QR code will pop up but there is a QR code so you can look at that paper and use the calculator with them. These slides will be available. One of the biggest things I’ve struggled with whenever we were talking about this presentation is the difference between providers and patients. I thought for the longest time that I really understood my patients and had a better sense of what they were going through. Then the voices study came out. It looked at the real-world data on patient perspectives versus physician perspective. The numbers weren’t gigantic. But they showed a common thread where number one Camaro patients are cycling their antihistamines. Which we see not infrequently reported to us in patients who have allergic. Whenever we talked about them, if they were not controlled and we did step them up, a lot of providers had a much higher assumption that they were responding to those therapies. One in four patients, which is lower than what we classically tell ourselves that we are complete responders to antihistamines, about 75% were partial or completely nonresponders. That was in patients who truly did have a diagnosis. And it told us that we shouldn’t just go under assumptions. Whenever we look at everything, there was a survey separately , and what was looked out was the difference between how much we had control with patients versus with physicians. Physicians by far and away reported less sentimentality in our patients and better control than patients reported. Patients reported about 20 percentage points higher symptomatology, even when they were not on medications — sorry, even when they were on medications. That wasn’t specialist specific. It wasn’t just allergist. It was dermatologists, primary care doctors. It said that we have room to get better, the patients with antihistamines, while we assume they will respond, sometimes we need to have more frequent visits to make sure that we don’t miss it. Also, make sure that we do SS a lot of their — we do SS a lot of their comorbidities. Including the mental health aspects. There was a much higher rate of anxiety and depression then we realized. For our systemic therapies, we have three FDA approved a systemic therapies. I think understanding the mechanism in where in the process of mast cell Digg generation do we think about the first therapy was called Omalizumab. Omalizumab is a humanized antibody that targets IGE.

The challenge with that mechanism is when we have had other agents, a higher affinity, we realized that the mechanism is not entirely driven through IGE binding. It is probably more to factorial of down regulation of the allergy antibody receptor on mast cell’s. It trapped autoantibodies that were forming and it affected the bound IGE on B cells. Dupilumab, which has been utilized in a number of allergic diseases, is an agent that started to come over the last year, that affects the skewing toward allergy cells. It tends toward not in the mast cell but works on the T cells and B cells to make sure we are not skewing toward making more IGE, or even affecting class switching of our antibodies, which makes sense why it takes the time it does and also may be a better option for some of our nonresponders for that. But also our patients that maybe have type 2b endotypes. Remibrutinib is the newest on the block. Remibrutinib is an oral agent. An oral BTK inhibitor. We will talk about BTK inhibition in a second. I think it’s something that we are trained that BTK equals a very specific disease that we see in young males at a young age. Our colleagues with hematology have been using BTK inhibitors more widespread, and having a very specific BTK inhibition will affect our intercellular signaling through our r1 receptor and have better protection directly underneath our allergy sectors. Like I said, Omalizumab was the first biologic that came out. It specifically works directly on the first step of mast cell activation. It is approved in 12 years and above. There are two doses paired low-dose and standard does. I don’t often use the low-dose. I tend to prefer the standard dose. It is a fixed dose so it is something that does set us up as compared to our patients with allergic asthma or patients with food allergy. There is good literature that looks at nonresponders or partial responders with options with that does, up in does, going from 300 milligrams 14 and increased interval or doing both. It is a little harder to get it approved and that way. There is work that can be done.

It does work as far as those dose escalations. It is approved for allergic asthma, and IgE in food allergies. Omalizumab is a great medicine. The newer kids starting to come out is Dupilumab and I will talk about the other agent. Dupilumab was approved in 2025. It has been around since 2016 for other indications, including asthma and more recently — And more recently with others. In CSU, it is the same as the adult dose we think about. Is a prefilled syringe, 300 milligram every two weeks. Approved 12 and above for people who have chronic spontaneous urticaria. Remibrutinib is the other one. If you have gone to any of our annual conferences, if you like the signs are everywhere for Remibrutinib. It’s the only one that is 18 and above. It is an oral agent that is done as 25 milligrams twice a day. It does not have any other current clinical indications. It is metabolized through C YP3A4 enzyme. It is the same enzyme that metabolizes antifungals and channel blockers entertain antidepressants. If you’re patient has CSU that also is on that, we may have to talk about dose adjustments. If they are also on antidepressants because of comorbid mental health conditions, we may need to talk about how we make adjustments to dose to make sure we don’t run into super therapeutic levels and affect everything. Before I talk about efficacy, I want to talk through the scoring system. The scoring systems utilized are either the you a S, urticaria activity score. Urticaria activity score, you have a score for how many wheels or hives they are having and how much itching they are having. A patient looks over the last week and they self assess from mild to severe. You get a score for each of those from zero to three. You do that for each day and you track. For the urticaria control test, that one is a little different. That is four questions that you go on. The UIS, high scores are bad. It tells you you have a lot of disease that is ongoing. The UCT, urticaria control test, the lower the number is, the less control. 16 for UCT is good. That is typically the one I use often clinically. Clinical trials will reference the you a S, and there is the into edema activity score looking at swelling. I will reference that in a second. Another quick plug is for the cruise app.

There is an app that helps patients track their symptoms, that is the QR code. It helps give you their UAS. I encourage my patients to download that so that they can help me know how symptomatically are so that we can make sure that we are coming at them with evidence to guide the therapy. It comes in many different languages so you actually can tailor to your patients, no matter whether they are inside North America or outside. Knowing that as far as how we define effectiveness, we focus on the UA asked –UAS. UAS7, over the last seven days, complete control is talked about in terms of zero, well-controlled is less than six. Omalizumab, their trials, all the way back in 2015, really showed about one third of patients will have a complete response. Which is different than how many patients have type one or type 2b. 65% maximum will develop all controlled UAS. After we stopped it, the symptoms came back. It is something we have not gotten into disease modification yet. As we have been using Omalizumab widely, we have been trying to figure out why there are some nonresponders coming so not in the clinical trials but after the clinical trials, we started to look at it. We know certain markers are predictors for prolonged chronic urticaria. We didn’t have a good way of identifying what were nonresponders for medicines? In Metro specter of regrouping, we found some biomarkers that may have some indicators for lack of response. It is the combination together of a low, defined as less than 40. A positive CU index peer that looks for type 2b CSU, or that IgE targeting IGG. Saying hey, this is something that will not be helpful by an anti-IgE. They defined as a low blood into histamine content. You can get it and most available labs and get a CU index now in our larger commercial labs as well.

There has been some literature looking at the degree of positivity for the fibroid peroxidase level. The higher that it is, the more likely they may not be responders. Which goes along with their skewing not toward a higher IgE level but toward a lower IgE level. Previously, there was a lot of looking at positive skin testing where you take the patient, spin it out to isolate it and skin test with it. That did correlate nicely with the type to be — type 2b. Dupilumab, whenever they did their trials, their trials were called Cupid. They took systemic therapy naïve patients. So they took patients that had never been on a systemic therapy. With the mechanism of action where it targets those T cells and B cells that skew toward making IgE, it took longer to have an impact on those cell, on affecting IgE production. While Omalizumab started in 12 weeks, Dupilumab did not start working until 24 weeks. It had a higher effect in patients who were Omalizumab naïve that were biomarker agnostic. They didn’t have specific biomarker that had to predict whether they would respond. About three out of 10 people will have complete response. About 40% will be well-controlled. In little bit on the lower side. For our nonresponders, even though Dupilumab was a biomarker agnostic, they didn’t have the biggest effect in that group. It was only more mild. I want to show you if you are going to commit to Dupilumab, that one took longer. It did catch underneath half of the patients. It did work well in the right grouping. But it may be something we need to make sure we are treating. The newest kid on the block, Remibrutinib, their trials were called REMICs. They had around the same levels, around 20% to 32%. Completely responding by 12 weeks. The interesting thing, because of the mechanism of action, because it was an intracellular agent that could start working fast, the initial response was noticed in the first one or two weeks. One third of patients can come back and be like, yes, I’m a responder. You had separation from placebo even as early as one week. 50% of patients were well-controlled. They had sustained efficacy while they were on therapies.

The Remibrutinib group, it was regardless of their IgE, there CU index, or prior treatments. It became an interesting question of which one is going to be the right therapy. I like to see things next to each other. We show different pictures with fact. And we show, they all respond, but we don’t have as much guidance on which one is the right therapy. Whenever you look at it, not everyone response to it. Not everyone that didn’t respond to one therapy will respond to another. I think it is a big question. I will talk about head-to-head studies in a second. There is not much. I think treating comorbidities, since we know 30% of patients do have inducible Arctic area and we know it is seen at a high rate in patients, in isolation or with their urticaria. We realize looking at the mean difference or the change in comparison for angioedema, urticaria and Remibrutinib both had a reduction in angioedema activity. Omalizumab may have had a higher reduction in their angioedema activity score. About 15% compared to a person. It may be the choices we say hey, what is your major symptom, are we having angioedema. There is more data on Omalizumab in the chronic inducible urticaria population. If you do have a patient that has comorbid chronic inducible urticaria, they may tend to do better on Omalizumab. Where whenever they have looked at real-world data through the you care network, they showed — chronic inducible urticaria are younger but treating with Omalizumab when they are younger, you can get away with getting them off of things. They didn’t follow them and say how many people relapsed. But the younger patients may be able to induce remission for chronic inducible with chronic spontaneous overlap. Remibrutinib is being studied in chronic inducible urticaria. I don’t have a reason to suspect it would not work. Dupilumab didn’t include that. It only had minimal efficacy in chronic inducible. If you have a patient that has chronic inducible urticaria, we may not want to pick Dupilumab for everything. When we talk about head-to-head trials, this was a plot that Derek Chu put out, whenever there was an update to some of the literature as far as how we will do a great analysis. The thick bars are how many trials into cap — in comparison. Whenever you see a placebo at the top, they are comparing a double line trial, which is the gold standard. It will notice there is only a couple of studies that compared to each other.

We have looked at Omalizumab compared — that compared to other things and we have looked at novel agents compared to Omalizumab. To do a better job of doing placebo to therapy her. We have not done good high-quality evidence to compare them. We are left sitting here in to do comparisons to her the best of our ability. We compared Omalizumab high-dose, standard does, and low-dose. Remibrutinib and Dupilumab. In general, if you have that activity, we know there is probably faster efficacy with Omalizumab 300 and Remibrutinib. Especially if there is angioedema. Those tend to be our preferred aspects better than Omalizumab. We don’t know about Dupilumab with angioedema. That something we are still figuring out. The big question will be about safety. There was a comparison for the difference comparing the patient’s in the clinical trials compared to placebo. It did look like Omalizumab had more of our reduction. This was before the pooled analysis with REMICs one and REMICs two. Whenever I commit to a systemic therapy, I want to set the standard. I want to set the expectation. They will not call me the next day and say, I didn’t respond. Four Omalizumab and Remibrutinib , I say give me at least three months. Give me three months. Usually, you know earlier. Both for Omalizumab Remibrutinib and Remibrutinib. Remibrutinib you can know in the first two weeks. Omalizumab, you really do know by 12 weeks sometimes they are a little sooner. Even partial responders, we can have some signals that they will improve, but they have washed out during the last week. For Dupilumab, you need to set the expectation. I typically will show you how I approach a patient with CSU at the end of how I think about that. Let’s have about adverse events. That will be the big question. Omalizumab has a black Spock — black box warning, risk for anaphylaxis. Dear .1 to 0.2. Whenever you look at meta-analysis, it typically occurred within 60% of two hours of the first three days. That was in the asthma studies. It was impose marketed analysis. But it wasn’t noticed in the food allergy studies.

Now that we are getting more data on it, I do think it will, be a question we need to revisit as far as what is the true rating for everything? I don’t think we fully know. It tended to be in people who had a history of anaphylaxis. It is an injection site, there is ocular surface disease in facial dermatitis. Some were starting to see more often with eczema. I’m going to give a whole slide to the BTC inhibitors. I talked about BTK deletions when we talk about that. I think the blockade of BTK will be something that is scary to people. When we looked at Remibrutinib, through the clinical trials, the things that stuck out to me were normal things that can occur to people. Headaches. It was a higher rate. BTK as a protein is present in platelets. We do know that whenever they saw them in the clinical trials, my patients on BTK inhibitors, those — it was, oh, they are there. But they didn’t have to be treated. They didn’t have true blood loss. They didn’t have to treat it. It does raise questions in our adult patients that are going to get surgeries as do we need to withhold it? That’s a question I’m asking myself. Do I have to hit pots? The biggest question is going to be the immunologic consequences. In the phase two trials, and REMICs one and REMICs two, they were doing those findings. 25 milligrams, 50 milligrams, 100 milligrams. At the 100 milligrams, four times the dose we are using, there was no change over a year. The graph you see there is what happened to patients, conglomerate of IGA ended in unchanged. That’s what we want to hear and see. There is a poster that came out right after this which looked at vaccine response after exposure. They took patients on 100 milligrams of Remibrutinib twice a day and said, you will continue it through, versus you are going to pause for 21 days around the influenza and pneumococcal vaccine. So they will take it for eight days, have a week washout, and pause for three weeks, then they checked four weeks later. If you pause, you didn’t have any effect on vaccines. If you took it straight through, there was a reduction in response to hemagglutinin. There was not as robust of a protection for immuno cockle. I think it is important to say, as you are counseling patients, we know a lot. But there are some things we don’t know yet. Making sure you are being completely transparent, it may have something. If we have to vaccinate, maybe we need to pause so we can be sure we have an adequate response to a vaccine that somebody needs.

The clinical outcomes for that, even though we talk about the vaccine tighter data, it does need to be replicated on a much larger scale. And at the doses we will use. Remibrutinib, the prescription dose is 25 milligrams twice a day. It’s not the dose they used in this poster. How do I choose? I counsel my patients starting at the top era I ask, how much is it bothering you? Do we want to pursue systemic therapies or do we not? What’s their preference? And what is our coverage for it? The best medicine in the world, getting covered by insurance will be a strong challenge. If they have a strong feeling for injection versus oral, that is a first step. I see predominantly kids, but whenever I have somebody that is 18, Remibrutinib is only 18 and above. I think there will be some safety questions the younger it goes as far as what is safe, what’s not safe. If you have someone who is 12 years and above, I think you have choices. Which is a great thing. Whenever I counsel my patients, I think about it if they are the worried family. They want a larger body of evidence. They want and are willing to wait 12 weeks. They are OK with once a month injections per they also have comorbid chronic inducible urticaria. I’m starting to check the IgE and say, are they elevated IG, do they have a CU index? I go back and forth on the antiviral proxy. As we start to have better testing and better cutoffs for thorough proxies, may be that is they that helps guide us. I think Omalizumab has the biggest body of evidence. I use Dupilumab in my patients that have other comorbidities. If they want to treat their asthma and their dermatitis and chronic rhino situs, then I think we need to prioritize one versus the other. Even though we know chronic spontaneous urticaria has a lot of implications and impacts on quality of life, some patients don’t view it that way. We have to go with what their major symptom is. The nice thing about Dupilumab is we can do it at home. We can do it every two weeks. Can do it in our lab agnostic patients. If we have a patient that does not have good lives, and makes me think Omalizumab will be successful they have — then I really do think about that. Remibrutinib, it is, I want relief now. I want it now and I’m willing to take it. You have to have adherence to a good oral medication this is a twice a day medication. Think there will be growing data and there is data on that. I think especially for our patients that have low IgE, or that have that chronic urticaria index, our type 2b patients. I think they are a good group to give a slightly different process. We are living in a time where we are having new choices. There is another BTK inhibitor in the work. It is in phase three trials and it will be looking at patients who did on the debtor did not respond to systemic therapies. It will be three times a day. Similar to what we saw with Remibrutinib. It is safe. They will be effective.

The dosing strategy will be challenging. Three times a day will be more cumbersome. But they worked in urticaria, chronic spontaneous urticaria. And they aren’t seeing a lot of the immunologic concerns. But I think we still need more data on patients with these inhibitors. One of the biggest things of excitement was the c-kit inhibitors. C-kit inhibitors, that is a market for survival four masked cells. It is making sure that it continues to be around. That was presented as far as a phase two trial. Every seat week injection. They actually had about 62%, similar to what we saw with Omalizumab, as far as well-controlled. UIS less than seven. The interesting thing is that the response was as fast as the oral CTK inhibitors. It didn’t matter their biologic responses. The coolest thing was after they stopped it. They had some disease modification. That’s where we need to put our emphasis. How do we use medicines while we are on it? The adverse effects are something we will pay attention to for C-Kit Inhibitors. It had some asymptomatic that was more mild, had some skin and hair changes. It really is an exciting time to be taking care of patients with chronic urticaria. There are bio similar’s that will target IgE. There is an — survival signals for mast cells. A siding on mast cells that actually have induction of degranulation. We are starting to look at our complement — RC five receptor as far as how we can do it. In a lot of our patients who may not have type one or type 2b, they may be more responsive to other therapies. Those are still in clinical trials. There’s not enough data to help guide us. There has never been a better time to take care of allergic skin diseases. The conclusions are chronic urticaria can cause a big quality-of-life impairment in our patients. We need to make sure we are available in talking them through the choices. The diagnosis is clinical and needs to be confirmed every time. Labs right now are not always the most beneficial, but they are starting to be paired we will work on our biomarkers to make sure we have the best choices. Antihistamines are the first step. We now have biologic and systemic therapies. All of them work, which is great. I’m happy to take any questions. Happy to answer everything to the best of my ability, as far as everything goes.

Ruthie: awesome. Thank you so much for that presentation, and sharing your wisdom and expertise on the latest treatments. We definitely have some questions. Let me get those we have one question related to the scoring, CSU scoring option. If you could please go over that once more, just to make sure that they understood it.

Dr. Dunn: Gotcha. The two major scores we use are the urticaria activity scores, and there is the urticaria control test. The UCT is probably used more clinically. I tend to use that because it’s faster. Is looking backwards over the last month, their recollection of how much it is impairing quality-of-life. That score is from zero to 16. It is based off of five questions where you have five multiple choice you get to choose on how bad this is bothering an individual. That is more supple fight because it — more simplified because it lets people to look retrospectively over a couple months. The you a S –UAS, is more day today. That one, you have to think over a one-week period. Each individual day has its own entity. They say, in this day, how many wheals did I have? From none to severe. Whenever they talk about it, they rank it on a scale from zero to three. Then they take the itching score, from zero to three, and that gives them a single day score from zero to six. They do that for every day and you added together. Your UA asked score that is high is bad. Where UCT, low is bad.

Ruthie: Thank you for that. We have a couple more questions. One is regarding managing expectations. He mentioned it in your presentation regarding some patients on Omalizumab that may take months to fully respond versus weeks with the BTK inhibitors. The question is, how do you set expectations with your patients, and at what point do you decide that it’s time to switch gears?

Dr. Dunn: I always tell them when I expect them to respond. Whenever I decide a therapy — if I’m going to pursue Dupilumab , I always say, which of these things that you have going on are your top priorities? I even have them rank it. My eczema is my number one. Great, OK. If that’s what we are thinking, these agents will not touch that. If I’m really thinking about chronic spontaneous urticaria, and then saying, great, these are the choices. This one, we will know fast. For Remibrutinib, I still set the expectation that I’m not going to know until 12 weeks. I may get some calls back and you may call me in a week and say, I am a responder because a third of patients will know in the third — in the first week. I tell them they may seek response on the first weeks but you will see maximum relief by the 12 weeks. Omalizumab, I tell them, we are committing to this for 12 weeks. We are committing ourselves to try this for three months. We may need to make adjustments from dozing because the first three injections have a prolonged weight, I do that in my clinic. I check in periodically during that time. A lot of my patients on it for chronic urticaria, I have a suspicion within the first one to two months that we see that improvement in the first couple of weeks. Even whenever I lay out those choices, aioli set the expectation. We will be committing for three months, and then six months for Dupilumab. I may no sooner but I’m not going to know fully before that. I set that expectation of, we may have good days and bad days. I want to make sure we look back over the three months to have that longer amount of data. I don’t want to get caught in the days. I think there some literature starting to look at, do you start one agent that will know fast, and if you don’t have response after four to 12 weeks, then change? The urticaria guidelines frown upon appeared just commit to 12 weeks so we have enough data.

Ruthie: Thank you for that. There is another question. What would you suggest for someone with multiple autoimmune’s, including thyroid, that are already taking something a day but have severe itching?

Dr. Dunn: Remember, with UAS, that falls into that category. That is the nice thing about the UIS –UAS versus the UTC. I would offer them, if they want to continue doing oral agents, you can do the leukotriene. Receptors. . Talking to them about that. I would say if you have multiple autoimmune conditions, I tend to at least right now, I think you could do either remembered men –Remibrutinib. I tend to have more success with one of those two. It depends on what their autoimmune thyroid levels are. At may change my decision.

Ruthie: OK. We will take one more question before we wrap up. For those more complex patients, like CSU with inducible triggers or angioedema, how are you thinking through treatment selection, given the difference in data between these therapies?

Dr. Dunn: Can you ask that one more time?

Ruthie: For more complex patients like CSU with inducible triggers or angioedema, how are you thinking through treatment selection given the difference and data between these therapies?

Dr. Dunn: I think it is the reason we need head-to-head studies. I’m going to get up on my soapbox for two seconds. I do think we need better work on our biomarkers. One of the things that we are realizing is a lot of this is retrospective data. We need prospective data. We now are taking it forward and saying great, we know they didn’t respond previously. But now let’s use that in clinical practice to predict it. In our more comfort gated patients that have inducible urticaria or overlap with different phenotypes, the clinical description of inducible and spontaneous. I have a preference and we need to have more head-to-head comparisons. There is a head-to-head comparison ongoing for Remibrutinib versus Dupilumab in a four week trial. I know that result is going to be that Remibrutinib is probably going to work faster. I’m hopeful that I will be learning something clinically from that. And I love to be wrong and love to learn something new from it. I think whenever I have someone who has a lot of overlap, I have a tendency to not only address the cofactors that I can treat, as far as how we keep them warm, if they have a cofactor that is contributing, is there temperature. But I also tend to lean more into anti-IG to make sure that we are treating it for them. If you have more data for chronic inducible urticaria at this time. There is not great studies of this one verses that one. I think that probably is higher efficacy for Omalizumab in that group where you have some blending. It is still a big question. Clinically, I don’t think I have the greatest answer because I don’t think we have done those studies. And I think we need to do those.

Ruthie: Thank you for answering that. This isn’t necessarily a question, just wanting to try something as we end our webinars. What is one practical take away you would like clinicians to apply to their very next patient with chronic urticaria?

Dr. Dunn: I think we need to listen to them and what their priorities are. We need to sit down and say, how can I actually help you? I can give you medicines, talk you through it. We have the head knowledge of how we want to do it. We need to sit down and say, what are your priorities? Also making sure we are not overestimating it. . That saying, great, you are in good control because you are on antihistamines. But is this the right time to pursue this? And let them make the choice for their own health.

Ruthie: Awesome. Thank you so much, Dr. Dunn, for this presentation. We really hope everyone has gained valuable insight to take back to their own practice. In a few days, Zoom will email you a link to the recording as well as supplemental resources, and a link to download your certificate of attendance. We hope you join us next month for our webinar on eczema and other any and related skin diseases and skin of color. On behalf of everyone at the allergy and asthma network, we thank you for joining us today. We hope to see you next time and have a great afternoon. Thank you again, Dr. Dunn. Dr.

Dunn: Thank you for having me.