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

Mark Lebwohl, MD

 from the phase 3b TOGETHER-PsO trial continue to spotlight the growing intersection between 

 These data, showing the improvements in skin clearance and weight reduction with combined ixekizumab (Taltz) and tirzepatide (Zepbound) versus ixekizumab alone, were touched on in a recent interview with Mark Lebwohl, MD, of the Icahn School of Medicine at Mount Sinai.

The analysis, looking at adults with moderate-to-severe plaque psoriasis and obesity or overweight, demonstrated significantly greater improvements by Week 36 of combination therapy use, with 27.1% of participants on combination therapy attaining both complete skin clearance (PASI 100) and at least 10% weight loss versus 5.8% of patients treated with ixekizumab monotherapy.

In the following segment of Lebwohl’s recent interview with 

 regarding his team’s findings, Lebwohl discussed the broader implications of the data for psoriasis care, emphasizing that obesity management should increasingly become part of routine dermatologic treatment strategies. Lebwohl noted the benefits observed of the combination therapy in TOGETHER-PsO may extend beyond ixekizumab specifically.

The following interview with Lebwohl highlights these findings, their potential implications for future psoriasis care models, and the evolving role of weight management therapies in dermatology:

Ixekizumab is currently the only biologic studied in combination with an incretin-based therapy in psoriasis and psoriatic arthritis. What broader implications do these findings have for future research into combination approaches targeting both metabolic disease and inflammatory skin disease?

 There are actually several questions buried in there. First of all, I do think that dermatologists should start adding weight loss drugs to their therapeutic regimens. That's number one. Number two, I think that the results of this can be broadly applied to weight loss drugs and to biologics or other treatments for psoriasis. If you add obesity drugs to our other therapies, they all work better. All you have to do is look at their pivotal trials. The patients who are obese did less well for virtually every treatment we have. There's a third implication in this…they're both anti-inflammatory, but we've not proven that using, for example, an obesity drug by itself will make psoriasis better, although there are studies that have shown that in a less way than what we showed with the combination.

Interestingly, also in some of the myocardial infarction studies, patients who were put on obesity drugs and did not lose weight still had a reduction in heart attacks, and that suggests that the incretins by themselves have an anti-inflammatory effect that helps the psoriasis. We have not proven that, but I think that might be another factor in why the patients get better. It’s still speculative, though.

Current psoriasis guidelines already recommend addressing obesity, but treatment is often still handled in silos. What barriers do you think exist between dermatology and obesity management today, and how might data like TOGETHER-PsO help encourage more integrated care models?

 Yeah, I think it's largely an educational barrier. You know, getting obesity drugs is already complicated because they cost a lot, so a lot of our medicine colleagues also have that problem. You'll explain to a patient, ‘Here's the choice, the drug's really good for you, there are many reasons why you should be on it, but it might cost several $100 a month.’ Mount Sinai, where I work, has a program where, last year, employees who are on incretins paid for the one that we used in the trial, tirzepatide, and paid $150 a month. I said that to one of my patients, who was just doing great, and he said, ‘Huh, you know, I save more than that a month in food.’

He loved the combination, as do almost all the patients. But I think we have to put it in perspective. There's a financial barrier, not just for dermatologists, and they're not going to deal with it any better than the dermatologist is. We are great at getting biologics for our patients. We have a whole team assigned to it. We have step therapy legislation. The problem is the copays on the incretins for the psoriasis biologics. Usually, we can have patient assistance programs, and we can often get the copays waived. But on the incretins, we can't. So the patients know that there's going to be a certain cost to it, and companies have different arrangements…I don't even know the name of the program, but for Eli Lilly, if you're on ixekizumab, you can get tirzepatide less expensively. So I have a lot of my patients on that program, because it's a lower cost.

What do you hope this research will continue to explore? What do you hope is the future of this trial program?

I think it would be good for us to be able to prove why they lose weight. We're doing a study like that at Mount Sinai as well, looking at the molecular aspects of why the patients have this synergistic effect of the two drugs. That's one piece of it. I think it would be nice to know if indeed the obesity drugs have an anti-inflammatory effect that's adequate, that we should be thinking of them just for that reason, for our psoriasis patients, let alone the weight loss. That's a question that I think will be answered at some point, because it hasn't just occurred to me, it's occurred to many people.

I think changing the way people practice is the biggest piece of this. You know, it can't be a one-shot study, and everybody forgets about it. There will be new psoriasis guidelines coming out. I'm hoping that they will include this information and encourage our colleagues to think about the combination when appropriate. I don't think anybody would doubt that for patients who are overweight or obese, it's appropriate. Many of the insurance companies require that patients have obesity if they're in the BMI range of 27 - 30. They have to be obese and have two comorbidities. Well, psoriasis should be considered one of the obesity-related comorbidities. If you have psoriasis and you're overweight, and let's say your BMI is 27 and not 30, you should be a candidate for these drugs.

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

Disclosures: Boehringer Ingelheim Pharmaceuticals, Incyte Corporation, Genentech USA Inc, Verrica Pharmaceuticals Inc, Pfizer, ER Squibb & Sons LLC, Hexal AG, Takeda Pharmaceuticals USA Inc, Novartis Pharmaceuticals Corporation, AbbVie Inc, Janssen Biotech Inc, Amgen Inc, Celltrion Inc, Almirall LLC, and Incyte Corporation.

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 May 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 May 25, 2026. 

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

Articles

Phase 3b TOGETHER-PsO data in adults with moderate-to-severe plaque psoriasis and overweight/obesity show clinically meaningful synergy between ixekizumab and tirzepatide by Week 36. Dual endpoints of PASI 100 plus ≥10% weight loss were achieved in 27.1% with combination therapy versus 5.8% with ixekizumab alone. Findings support routine incorporation of obesity pharmacotherapy into psoriasis management and suggest benefits may generalize across biologics. Implementation is constrained by education, access, and copay structures, while mechanistic work is pursuing anti-inflammatory incretin effects independent of weight loss.

This Q&A interview highlights the broader implications of the phase 3b TOGETHER-PsO trial for ixekizumab and tirzepatide in managing psoriatic disease.

Q&A: Implications of Ixekizumab, Tirzepatide Data for Psoriasis and PsA, With Mark Lebwohl, MD

Phase 3b Data on Ixekizumab, Tirzepatide for Psoriasis and Overweight, With Mark Lebwohl, MD

 suggest combining ixekizumab (Taltz) with tirzepatide (Zepbound) may significantly improve outcomes for patients with moderate-to-severe plaque psoriasis and obesity or overweight, according to Mark Lebwohl, MD, of the Icahn School of Medicine at Mount Sinai.

The 52-week, randomized phase 3b TOGETHER-PsO trial evaluated ixekizumab alone versus ixekizumab combined with tirzepatide in 274 adults with psoriasis and obesity or overweight. By Week 36, investigators found 27.1% of patients receiving combination therapy achieved both complete skin clearance, defined as Psoriasis Area and Severity Index (PASI) 100, and at least 10% weight loss, compared with 5.8% of patients treated with ixekizumab alone (

 < .001). Investigators also observed a 40% relative increase in PASI 100 responses with the combination regimen.

, Lebwohl said the findings reinforce growing recognition that psoriasis and obesity should not be managed separately, given their overlapping inflammatory pathways.

“We know that [for] obesity, the fat cells of obesity secrete cytokines that make psoriasis worse,” Lebwohl explained, noting patients with obesity often respond less effectively to biologic medications by themselves. According to Lebwohl, adding weight management therapy can improve biologic efficacy while simultaneously addressing broader health risks associated with obesity.

Lebwohl suggested the study may also influence dermatology practice patterns, predicting dermatologists will become increasingly comfortable prescribing anti-obesity medications directly for patients with inflammatory skin disease. He described monitoring requirements for incretin-based therapies as relatively straightforward and emphasized their potential benefits beyond weight reduction, including improvements in blood pressure, cholesterol, diabetes risk, and overall quality of life.

Lebwohl also pointed to related findings from the TOGETHER-PsA trial in psoriatic arthritis, where combination treatment similarly demonstrated stronger outcomes than biologic therapy alone. He noted weight loss interventions have increasingly become a core strategy when biologic treatments appear less effective in patients with obesity.

Overall, Lebwohl described the combination approach in his interview as a potentially important advancement in comprehensive psoriasis care, particularly for patients with obesity or overweight whose inflammatory disease may be amplified by metabolic dysfunction.

Armstrong et al. Addressing the Obesity-Psoriasis Connection: Prevalence, Incidence, and Comorbidity Insights from a Large US Population of 19.9 Million (2018-2024). Presented at Maui Derm, 2026. Accessed May 24, 2026.

Videos

This interview highlights recent phase 3b data from the TOGETHER-PsO trial on ixekizumab and tirzepatide for psoriasis and obesity or overweight.

Closing Thoughts on TYK2 Inhibition in Psoriasis

In the final episode, ‘Closing Thoughts on TYK2 Inhibition in Psoriasis,’ the panelists explore the culmination of their discussion on modern psoriasis care and offer closing pearls for clinical practice. Dr. Mark Lebwohl emphasizes that while every patient presents a unique constellation of desires, symptoms, and comorbidities, dermatologists are currently in a better position than ever to achieve high levels of clearance. He advises clinicians to run through a quick mental algorithm for every patient that accounts for factors such as smoking status, high blood pressure, and preferences regarding oral versus injectable administration. Dr. Lebwohl stresses that clinicians should never settle for just okay results, as tighter disease control directly reduces the risk of long-term complications like psoriatic arthritis and cardiovascular events.

Dr. Tina Bhutani-Jacques reinforces this message by encouraging providers to shed any lingering hesitation regarding the use of systemic therapies. She points out that the current and emerging classes of medications, particularly selective TYK2 inhibitors, are remarkably safe when paired with appropriate patient monitoring. The experts conclude by reminding clinicians that they are in a unique position to improve not just the skin, but the overall life expectancy and health of their patients. By focusing on shared decision making and the prevention of systemic inflammation, providers can ensure that even patients who are initially hesitant or satisfied with partial clearance understand the vital health benefits of more effective, modern interventions.

Thank you for watching this Peers & Perspectives series on TYK2 inhibition in psoriasis. Please subscribe to our newsletter for information on upcoming video series.

Learn how to personalize systemic psoriasis care, weigh comorbidities, and aim for rapid clearance to reduce heart and joint risks.

Closing Thoughts on TYK2 Inhibition in Psoriasis 

Emerging Updates in Psoriasis from 2026 AAD Annual Meeting 

In ‘Emerging Updates in Psoriasis from 2026 AAD Annual Meeting,’ our panel explores the most impactful findings from the latest clinical gatherings, focusing on how new data is reshaping real-world practice. Dr. Mark Lebwohl highlights the clinical debut of several new TYK2 inhibitors and the recent FDA approval of icotrokinra, the first oral anti-IL-23 receptor peptide. A major focal point of the discussion is the revolutionary data regarding the combination of GLP-1 agonists with standard psoriasis biologics. Dr. Lebwohl notes that in patients with a BMI near 40, adding anti-obesity medication led to a 40% increase in PASI 100 achievement and a 64% improvement in psoriatic arthritis measures.

Dr. Tina Bhutani-Jacques and Dr. Lebwohl examine the biological mechanisms behind these results, suggesting that weight-loss drugs may possess independent anti-inflammatory properties that benefit the heart and joints even in the absence of significant weight reduction. Dr. Lebwohl emphasizes that addressing obesity is now a mandatory component of psoriasis care, as certain types of fat secrete the very cytokines that drive disease progression. He shares his clinical approach to these sensitive conversations, focusing on longevity and health rather than aesthetics. The experts conclude that by integrating anti-obesity treatments with highly selective TYK2 inhibitors or biologics, clinicians can move beyond treating skin surface area to fundamentally altering the patient's systemic inflammatory profile and long-term survival.

Our final episode, ‘Closing Thoughts on TYK2 Inhibition in Psoriasis,’ features the panelists offering practical advice for clinicians navigating the modern treatment landscape. Dr. Bhutani-Jacques and Dr. Lebwohl encourage providers to prioritize total skin clearance and proactive comorbidity management as the standard of care for all patients.

Learn how dermatologists tailor psoriasis treatment—topicals, phototherapy, pills or biologics—using shared decisions, severity and comorbidities.