Q&A on Treating Psoriasis, Obesity with Tirzepatide and Ixekizumab, With Neal Bhatia, MD

On February 18, Eli Lilly and Company released new phase 3b findings suggesting adults with moderate-to-severe plaque psoriasis and obesity or overweight treated with ixekizumab (Taltz) combined with tirzepatide (Zepbound) saw significantly greater improvements in skin clearance and weight reduction versus ixekizumab alone.1

These data, drawn from the open-label TOGETHER-PsO trial, were discussed by TOGETHER-PsO investigator and director of Clinical Dermatology at Therapeutics Clinical Research, Neal Bhatia, MD.2 Bhatia’s HCPLive interview, regarding these data on ixekizumab and tirzepatide as a potential combination therapy for adults addressing psoriasis and weight loss, is summarized in the following Q&A:

HCPLive: We wanted to ask you about the release by Eli Lilly that came out regarding ixekizumab and tirzepatide. How significant are these findings showing improved skin clearance and weight loss with the combination therapy, as opposed to only the monotherapy, particularly for patients with psoriasis and elevated BMI?

Bhatia: Well, it's fortunate that one manufacturer makes both drugs. It makes eventual access to both down the road, as well as you know the utility in the trial for tirzepatide and ixekizumab together. I mean, mechanistically, it makes a lot of sense when you see what GLP-1 agonists do under the hood with the immune mechanisms. There's a lot of impact on NF-κB as a neurotransmitter; both interleukin-1 and interleukin-17 pathways are actually inhibited, or at least modulated by their impact. Tumor necrosis factor, which obviously we know again with psoriasis, has a lot of roles, as well as being suppressed just by tirzepatide alone.

Then you add just the active ingredient of…an IL-17 inhibitor. So I think from the standpoint of the combination of the two mechanisms, you really have a lot of potential synergy, as well as activity against the immune cascades that work. When you think about a patient who has a high BMI, for example, they might be experiencing issues in terms of insulin resistance, in terms of the psychosocial changes, obviously, that go along with being heavier. Then, of course, the lack of ability to exercise some of the other components of intragious friction and all those other components.

There is a lot of evidence supporting that if you can find weight loss methods for these patients, they will do extremely well. I think that expands not just from psoriasis, but you'll see that with hidradenitis suppurativa as well. But in this study, they actually show that around 40% of the subjects who were treated with both drugs with both active agents experienced PASI-100, as opposed to ixekizumab alone. I think from that data alone, you see the benefit of the additive effect. Obviously, it's a shot a week for those patients who are on the tirzepatide arm. But you know, many won't care, to be honest with you, as long as they see what they're getting in terms of quality of life and improved health.

HCPLive: There's a lot of talk out there right now about GLP-1 agonists in dermatology. What is your opinion about the potential for future research regarding tirzepatide alone?

Bhatia: Well, that would be interesting to see what tirzepatide alone could do, maybe in a pilot study or a proof of concept study. I don't think it would be something that would reach a phase 3, pivotal type of trial where you're looking for a label. But to just see the individual effects, you could probably make the case that an additive arm of tirzepatide alone to the combination of the two and ixekizumab alone. It'd be an interesting comparison of those three side by side, not just the combination of the two.

Intuitively, I would think you still need an anti-psoriasis mechanism, but there could definitely be some improvement. A lot of psoriasis patients, they'll say they cut out drinking alcohol, they improve their diet, they start exercising, and their psoriasis improves. Is that a function of insulin resistance improving? Is that a function of the anti-inflammatory improvements from their quality of life changes? There's a lot of evidence to bring that up as well. So to say that a GLP-1 agonist might provide that same benefit, I could see how that would happen. But you know, if dietary and exercise modification does that as well, then I think we have the scientific benefit for the scientific knowledge from there alone.

HCPLive: Beyond psoriasis, do you see a potential role for GLP-1 or dual incretin therapies for other diseases like HS?

Bhatia: Hidradenitis suppurativa is probably the next obvious step, and again, there are some diseases that are BMI-dependent. There are some that kind of go along with those methods [for determining if] you improve their disease by improving their weight or by improving their BMI. I think the sky's the limit in the opportunities with the inflammatory cascade…

HCPLive: There's been increasing discussion about adipose tissue as an active inflammatory organ. How does that concept sort of reshape the way dermatologists could be thinking about treating patients with obesity and chronic inflammatory disease?

Bhatia: Adipose tissue has immune effects, just like the impact of insulin growth factor, maybe some other neurotransmitters that are impacting other cascades. It kind of goes in reverse. If you reduce the amount of adipose tissue, would you see a reduction in insulin growth factor? You know, we're seeing adipose tissue can be a strong source of inflammatory mediators. I think the sky's the limit of what we can discover by, again, changing someone's body mass index, for example, or adding these therapies to treatments that might not be successful…So there are a lot of different ways to look at the potential for improvements there.

HCPLive: From a practical standpoint, what would you say is the value of integrating metabolic management into dermatologic care, rather than referring weight management entirely to primary care or endocrinologists?

Bhatia: I think dermatologists, we should have no problem writing Metformin for a lot of patients who might be a little heavier and who have insulin resistance that's affecting their skin disease. We should have no problem writing GLP-1s. I mean, patients are getting it themselves. We dermatologists, would be completely missing the bus if we're not, you know, endorsing these drugs when they're appropriate for the right patient. But I also think just talking to patients simply about the dietary benefits of exercise, of weight loss, of cutting out alcohol and cigarettes, and watching their diet, is helpful. I mean, we talk about it with rosacea, we talk about it with other integrative-type processes.

I don't think there should be any reason why we shouldn't be taking some of this on ourselves. I mean, getting the help of a dietitian should also be something to turn to, but not everybody has that access or the time…I think we just need to have that extra couple of minutes conversation with the patients while we have them in the audience, and the same with their spouses and the parents of their kids. When we think about young kids with eczema, if they're a little bit heavy, you know, putting them in a good weight loss program would definitely help.

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

Bhatia reported serving as an advisor, consultant, and investigator for AbbVie, Almirall, Arcutis Biotherapeutics, Beiersdorf, Biofrontera, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Dermavant Sciences, EPI Health, Ferndale, Galderma, Incyte, ISDIN, Johnson & Johnson, La Roche-Posay, LEO Pharma, Lilly, Ortho Dermatologics, Pfizer, Regeneron Pharmaceuticals, Sanofi, Sun Pharma, and Verrica Pharmaceuticals.

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 March 6, 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 March 6, 2026. https://www.hcplive.com/view/ixekizumab-tirzepatide-effective-together-psoriasis-obesity-overweight.