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

New topline results 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 moderate-to-severe psoriasis and obesity or overweight.1,2

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 (P < .001). These findings and their significance were highlighted in a new interview by HCPLive 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 HCPLive highlights Lebwohl’s discussion regarding these new findings on ixekizumab and tirzepatide:

HCPLive: 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?

Lebwohl: 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.

HCPLive: 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?

Lebwohl: 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.

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

Lebwohl: 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.

HCPLive: 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?

Lebwohl: 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.

HCPLive: 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?

Lebwohl: 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.

References

1. 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.

2. 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.