Mark G. Lebwohl, MD, the dean for Clinical Therapeutics at the Icahn School of Medicine at Mount Sinai,

Mark Lebwohl, MD

Remibrutinib Shows Rapid Symptom Relief in CSU, With Mark Lebwohl, MD

Pooled data from the phase 3 REMIX clinical trials

 suggest the oral Bruton’s tyrosine kinase inhibitor remibrutinib may reduce daily disease activity within 12 hours of treatment initiation in patients with 

. Investigators presented the results at the 

2026 American Academy of Allergy, Asthma, & Immunology (AAAAI)

 spoke with investigator Mark G. Lebwohl, MD, the dean for Clinical Therapeutics at the Icahn School of Medicine at Mount Sinai, who discussed the clinical implications of these findings and remibrutinib’s impact.

“I vividly recall a woman who was coming to me planning a wedding,” Lebwohl said.

The woman had come covered in urticaria, which had been on her skin for months. With remibrutinib, she could quickly improve her symptoms.

“The ability to give that rapid improvement is such an instant relief, which is greatly appreciated by patients,” he continued. “Often when we start treatments that take a while to work, the patients are not aware [of this fact] ... and they become skeptical that the treatments [are] not working. One of the worst things that happens with some of the other drugs is [that] you're starting a patient on a treatment for chronic urticaria, and they think they can then stop their antihistamines. It turns out, for many of the other treatments, that's a huge problem because the treatments don't kick in sometimes for days or even weeks. With remibrutinib, the treatment kicks in right away.”

The analysis pooled results from the phase 3 REMIX-1 and REMIX-2 trials evaluating remibrutinib 25 mg twice daily in patients with CSU inadequately controlled with H1-antihistamines. Across both studies, 606 and 306 participants received remibrutinib and placebo, respectively. Investigators examined daily disease activity using the daily Urticaria Activity Score (UAS), which ranges from 0 to 6 and incorporates both hive severity and itch intensity.

At baseline, mean daily UAS scores were 4.44 among patients receiving remibrutinib and 4.30 among those receiving placebo. Within 12 hours of the first dose, mean UAS scores declined to 3.96 with remibrutinib compared with 3.99 with placebo. Improvements continued over the first week of treatment; mean scores reached 3.09 vs 3.92 on day 2 and 2.25 vs 3.49 by day 7.

The analysis also examined shifts in symptom severity bands over the first week of treatment. At baseline, only 1.3% of patients receiving remibrutinib and 0.7% of those receiving placebo were classified in the lowest UAS severity band (0–1), representing no or mild symptoms. Within 12 hours, those proportions increased to 6.5% and 2.4%, respectively. By day 7, 37.0% of patients receiving remibrutinib had reached the lowest symptom band compared with 9.7% of patients receiving placebo.

Lebwohl noted that evaluating daily symptom scores rather than relying solely on the traditional weekly UAS7 metric allows clinicians to better understand how quickly therapies begin working. With UAS7, it adds scores over the 7 days; the worst score a patient can get is 21.

“That doesn't really tell us what happens on day 1,” Lebwohl said. “We now have data that in the first 12 hours, patients on remibrutinib have improved.”

Another takeaway from the findings is that remibrutinib appears effective in patients who have previously failed standard therapies. According to Lebwohl, many individuals receiving advanced therapies for CSU have already failed high-dose antihistamines, a prerequisite recommended by current treatment guidelines.

Lebwohl also highlighted the potential impact of remibrutinib’s oral formulation on treatment decisions. While several biologic therapies are available for CSU, they are administered by injection. In contrast, remibrutinib is taken orally, which may influence patient preference.

The study showed adverse events were generally mild. The therapy does not require routine blood monitoring, and the main safety signal noted in clinical trials has been minor bleeding-related events such as petechiae, though Lebwohl has observed this less in practice than as reported in the trials.

Current CSU guidelines recommend omalizumab after failing non-sedating antihistamines. However, after the publication, the FDA had approved dupilumab and remibrutinib for CSU.

“I think all 3 of them, when algorithms or guidelines are developed…will be in the same space where a decision will be made,” Lebwohl said. “All 3 are…good options. Remibrutinib does have the advantage of being fast and being a pill.”

Disclosures for Lebwohl include Boehringer Ingelheim Pharmaceuticals, Incyte Corporation, Genentech USA, Inc., Verrica Pharmaceuticals Inc., PFIZER INC., E.R. Squibb & Sons, L.L.C., Hexal AG, Takeda Pharmaceuticals U.S.A., Inc., MAYNE PHARMA COMMERCIAL LLC, Novartis Pharmaceuticals Corporation, ABBVIE INC., Janssen Biotech, Inc., Amgen Inc., Celltrion, Inc., Almirall LLC, and Incyte Corporation.

Windom H, Machado P, Ortmann CE, et al. Remibrutinib Provides Fast Symptom Relief Within the First Week of Treatment in Chronic Spontaneous Urticaria, as Measured by Daily Urticaria Activity Score: Pooled REMIX-1/-2 Studies. 

Journal of Allergy and Clinical Immunology

doi:https://doi.org/10.1016/j.jaci.2025.12.045

Videos

At AAAAI 2026, Lebwohl discussed REMIX trial data showing oral remibrutinib reduced CSU symptoms within 12 hours and improved disease control.

 were recently released by Eli Lilly following the phase 3b TOGETHER-PsO trial, indicating ixekizumab (Taltz), along with tirzepatide (Zepbound), led to significantly greater improvements in both skin clearance and weight loss versus ixekizumab alone in adults with 

Among the team’s findings, 27.1% of patients at 36 weeks on combination therapy were found to have achieved both Psoriasis Area and Severity Index (PASI) 100 and at least 10% weight loss, compared with 5.8% on monotherapy (

 < .001). These findings and their significance were highlighted in a new interview by 

 with Mark Lebwohl, MD, TOGETHER-PSO investigator, professor, and chairman of the Department of Dermatology at Mount Sinai School of Medicine.

The following summary of his interview with 

 highlights Lebwohl’s discussion regarding these new findings on ixekizumab and tirzepatide:

We wanted to ask you a little bit today about the TOGETHER-PSO trial. Would you please tell us about the design of the TOGETHER-PSO trial and which questions the team sought to explore?

 Among the most difficult to treat patients, and this has been shown in literally every single study of psoriasis therapies, obese patients are harder to treat. When you look at the response rates in skinny patients versus obese patients with virtually every drug, except for the few drugs that are adjusted for weight, the response is much lower in patients who are obese. The endpoints that we made were rigorous….We were so confident that the combination would do well that we made PASI 100 the endpoint, which means 100% clearance of psoriasis.

There's no question as to whether the patient got better or not. [Many] are completely, completely better, zero psoriasis, not a dot. We also made a combination primary endpoint, which was the achievement of PASI 100 combined with at least 10% weight loss. In the group that got the combination of ixekizumab and tirzepatide, over 27% achieved PASI 100 with more than or equal to 10% weight loss. Of the ones who are treated with ixekizumab alone, only 5.8% achieved PASI 100 plus at least a 10% weight loss.

Now, for anyone skeptical about that, tirzepatide has already been proven to dramatically increase weight loss…Even with some of our good biologics, to achieve PASI 100 is quite an accomplishment.

You mentioned the population had moderate to severe psoriasis and elevated BMI. Why would you say it's generally clinically important to study these two conditions together, rather than treating them separately?

There are so many reasons; I could give an hour-long lecture on this, but we know that psoriasis patients are more likely to be obese. Obese patients are more likely to have psoriasis, so there is an interchange between the two. It has been suggested that some of the cytokine patterns released by adipose tissue in obese patients contribute to the development or worsening of psoriasis, and I would say that that is more than speculation. There's a lot of evidence to support that. But more importantly, in every single trial of psoriasis, when you look at the proportion of obese patients who get clear compared to the proportion of skinny patients who can get clear, the numbers are wildly different.

Many fewer obese patients are clear. The only exceptions to that are drugs like infliximab, which are given in milligrams per kilogram. If you take a very obese patient, they'll get much more drug because they weigh much more. That is not the case for most of the drugs that we have. Most of them are fixed doses. There are a couple of them, such as ustekinumab or bimekizumab, where you can increase the dose for obese patients. Certainly, some of our oral medications can have an increased dose for obese patients, but most of the drugs are a specific dose and not more.

So, it becomes uniquely important. The question raised by this trial is, does the tirzepatide itself have a direct anti-inflammatory effect? We don't know that from this trial. It's tempting to speculate that not only is the ixekizumab solving psoriasis, but independent of the weight loss, tirzepatide is contributing to an improvement in psoriasis. We can't say that for certain yet, and that's a trial that hopefully will be done, where we can look to see how tirzepatide alone is for psoriasis.

 What did you observe in terms of safety and tolerability with the combination therapy? Were there any surprises?

No, there were no new side effects. The only real side effect of ixekizumab has been the development of yeast infections. Those are not increased; the very uncommon inflammatory bowel disease flares on ixekizumab, those were not increased. The side effects of tirzepatide are well known. That's how we titrate to the dose. It's primarily GI side effects such as nausea, abdominal pain, diarrhea, and those were just what you would expect from ixekizumab alone. It was not increased by the addition of ixekizumab.

Based on these results, how do you see this combination approach potentially changing the way dermatologists could manage patients with psoriasis who also have obesity?

I probably have about 100 patients on tirzepatide plus a biologic. And you know, the reason for that is very straightforward. It's not just that we're making their psoriasis better, which we are. It gives us the ability to make their psoriasis much better, but at the same time, we make them feel better. We make them look better, we make them live longer, fewer heart attacks, less diabetes, less hypertension. Certainly, obesity is our main target. Even many cancers are reduced by GLP-1s and GIP, which is what tirzepatide is. I would say we're doing a lot for our patients beyond their skin.

Do you have any final thoughts just about this release? What do you hope it means to the world of dermatology right now to see weight loss drugs being used in combination to treat inflammatory diseases?

 I do believe that within a few years, most of my colleagues will be prescribing weight loss drugs. There are several reasons to do that in dermatology. This is not the only disease that is made better by weight loss. For hidradenitis suppurativa, we are using the drug already and seeing a benefit already. This, obviously, is all anecdotal, and it remains to be studied, but we are seeing that the role of obesity in HS is well established. Many forms of arthritis, including psoriatic arthritis, clearly benefit from weight loss. So, I think there's a lot of room to do it.

But when you think about the dermatologists who don't prescribe biologics, a lot of cosmetic dermatologists, one of my former residents has a very busy cosmetic practice. About 40% of her patients are on weight loss drugs, and they are prescribed by her. Their main reason for being there is for her to monitor their weight loss and their use of the drug. I think there is a major role for dermatologists, whether they are medical dermatologists, cosmetic dermatologists; it's a major role for us to use anti-obesity drugs. Hopefully, in the next few years, I think, my colleagues will be embracing that.

The quotes used in this interview summary were edited for clarity.

Lebwohl has disclosed serving as a researcher, investigator, and consultant for Eli Lilly.

Lilly's Taltz (ixekizumab) and Zepbound (tirzepatide) used together delivered superior efficacy in first-of-its-kind Phase 3b trial for adults with psoriasis and obesity or overweight. Eli Lilly. February 18, 2026. Accessed February 24, 2026. 

https://investor.lilly.com/news-releases/news-release-details/lillys-taltz-ixekizumab-and-zepbound-tirzepatide-used-together-0

Smith T. Ixekizumab, Tirzepatide Effective Together for Psoriasis and Obesity or Overweight. HCPLive. February 18, 2026. Accessed February 24, 2026. 

https://www.hcplive.com/view/ixekizumab-tirzepatide-effective-together-psoriasis-obesity-overweight

Articles

Phase 3b TOGETHER-PsO topline data suggest combining ixekizumab with tirzepatide improves outcomes in adults with moderate-to-severe psoriasis and elevated BMI, a population historically showing attenuated biologic responses. At 36 weeks, 27.1% on combination therapy achieved PASI 100 plus ≥10% weight loss versus 5.8% with ixekizumab alone (P<.001). Safety appeared consistent with known profiles, with no new signals. The results reinforce bidirectional links between adiposity and psoriatic inflammation and support broader dermatology adoption of anti-obesity pharmacotherapy.

HCPLive speaks with Mark Lebwohl, MD, about recent data on those with psoriasis and obesity or overweight treated with ixekizumab (Taltz) and tirzepatide (Zepbound).

Discussing New Data on Ixekizumab, Tirzepatide for Psoriasis and Weight Loss, With Mark Lebwohl, MD

A variety of new findings on psoriasis drugs were highlighted during the 

2025 European Academy of Dermatology and Venereology (EADV) Congress

 in Paris, including new data on icotrokinra, Johnson & Johnson’s first-in-class investigational targeted oral interleukin (IL)-23 inhibitor.

 care, as well as findings presented at EADV on the treatment of this inflammatory skin disease, the 

 team interviewed Mark Lebwohl, MD, on this topic. Lebwohl, the dean for Clinical Therapeutics and Chairman Emeritus of the Kimberly and Eric J. Waldman Department of Dermatology at the Icahn School of Medicine, was asked about what he feels have been the biggest changes in psoriasis care in the past 5 years.

Highlighting Recent Findings on Icotrokinra, Other Psoriasis Developments, with Mark Lebwohl, MD

“There have been many shifts in psoriasis care,” Lebwohl said. “We started out the last 5 years with a lot of biologics already on the market. There has been the introduction of newer ones, specifically bimekizumab, which is highly effective, [and it was] quite a breakthrough. One of the things, which started first out of my department actually, is when oral medications became available. It really made it easy to treat those patients who didn't want to go on injectable medications. But in addition, they had a number of other advantages.”

Lebwohl noted that if patients have difficulty responding to a single drug, combination therapy can be utilized. He then highlighted that the introduction of deucravacitinib, when added to biologics, enabled clinicians to treat many of those who did not have a strong enough response to biologic options.

“In addition, as monotherapy, deucravacitinib was very helpful, particularly in patients who did not want to go on systemic therapies,” Lebwohl explained. “One of the leading treatments we have, apremilast, is widely used, but significantly less effective than deucravacitinib. And that was shown in The Lancet papers on the pivotal trials where the 2 are compared. Having a strong oral medication with biologic-like efficacy was a breakthrough for us.”

Lebwohl was also asked about icotrokinra and its recent data released during EADV.

“Icotrokinra, from its pivotal trial data, looks like it will be one of the most effective treatments we have,” he explained. “It's a once-a-day drug, again, given orally, so it avoids injections. And I think it'll be a breakthrough. It's an exciting treatment for us. We now have a growing armamentarium of oral therapies with biologic-like efficacy, which is a breakthrough.”

The quotes contained in this interview were edited for the purposes of clarity.

Lebwohl has disclosed being an employee of Mount Sinai and receiving research funds from AbbVie, Arcutis, Avotres, Boehringer Ingelheim, Cara therapeutics, Clexio, Dermavant Sciences, Eli Lilly, Incyte, Inozyme, Janssen, Pfizer, Sanofi-Regeneron, and UCB; and serving as a consultant for Almirall, AltruBio Inc., Apogee, Arcutis, Inc, AstraZeneca, Atomwise, Avotres Therapeutics, Boehringer-Ingelheim, Bristol Myers Squibb, Castle Biosciences, Celltrion, CorEvitas, Dermavant Sciences, Dermsquared, Evommune Inc, Facilitation of International Dermatology Education, Forte Biosciences, Galderma, Genentech, Incyte, LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Sanofi-Regeneron, Seanergy, Strata, Takeda, Trevi, and Verrica.

Johnson & Johnson. Icotrokinra shows superiority to deucravacitinib in first reported head-to-head trials reinforcing promise of novel targeted oral peptide for treatment of plaque psoriasis. JNJ.com. Published September 17, 2025. Accessed September 30, 2025. 

https://www.jnj.com/media-center/press-releases/icotrokinra-shows-superiority-to-deucravacitinib-in-first-reported-head-to-head-trials-reinforcing-promise-of-novel-targeted-oral-peptide-for-treatment-of-plaque-psoriasis

Bissonnette R. Icotrokinra, a Targeted Oral Peptide That Selectively Blocks the Interleukin-23–Receptor, for the Treatment of Moderate-to-Severe Plaque Psoriasis. Presented at the 2025 American Academy of Dermatology (ADA) Annual Meeting. Orlando, FL. March 07-11, 2025.

During this EADV interview, Lebwohl speaks to some of the most recent developments in the psoriasis research space.

Key Takeaways and Considerations for the Use of BTK Inhibitors in CSU Treatment

Video content above is prompted by the following:

What are some key takeaways on the potential use of BTK inhibitors in the treatment of CSU that you’d like to share with clinicians managing this condition?

Panelists discuss how Bruton tyrosine kinase (BTK) inhibitors represent a promising new therapeutic class for chronic spontaneous urticaria (CSU) by offering rapid symptom control through targeted inhibition of both mast cell and B cell pathways, with newer agents like remibrutinib showing high selectivity, favorable safety, and robust efficacy in clinical trials that could position them as an important oral therapy option between antihistamines and biologics.