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

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.

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

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.

Patient Preferences and Shared Decision-Making in Psoriasis Care

In this episode, ‘Patient Preferences and Shared Decision-Making in Psoriasis Care,’ the expert dermatologists explore the nuanced process of transition from topical to systemic therapy. Dr. Mark Lebwohl explains that while a 10% body surface area (BSA) often serves as a traditional threshold, systemic treatment is frequently necessary for patients with lower BSA if the psoriasis affects high-impact areas like the palms, soles, genitals, or hairline. He emphasizes that the National Psoriasis Foundation provides crucial support for clinicians to advocate for systemic options when a patient’s quality of life is significantly impaired, regardless of objective coverage scores.

Dr. Tina Bhutani-Jacques and Dr. Lebwohl discuss how they navigate the "shared decision-making" conversation by presenting patients with the full spectrum of modern options, including ultraviolet light, oral pills, and biologics. Dr. Lebwohl notes that specific patient needs—such as the requirement for rapid clearance before a wedding or a job interview—often push the choice toward faster-acting biologics. Conversely, comorbidities play a decisive role; for instance, IL-17 blockers are preferred for patients with multiple sclerosis, while they are avoided in those with Crohn's disease. The experts also touch on the "moderate" patient population, noting that while some oral therapies have broader labels for less severe disease, recent head-to-head trials show that many patients find the convenience of an injection every three months to be superior to a daily pill. The discussion concludes by reaffirming that because every patient defines convenience and success differently, a personalized, conversational approach is the only way to optimize long-term adherence and outcomes.

The next episode in this series, ‘Emerging Updates in Psoriasis from 2026 AAD Annual Meeting,’ features the panelists discussing late-breaking data regarding next-generation oral therapies and the dramatic synergy between weight-loss medications and psoriasis treatments. Dr. Bhutani-Jacques and Dr. Lebwohl explore how these combined approaches significantly improve skin clearance and systemic health.

Explore how cutting inflammation in psoriasis may lower heart risks, and why new oral TYK2 inhibitors could broaden treatment beyond injections.

Mark Lebwohl, MD

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