Oral Treatment Advances and Weight-Loss Drugs in Psoriasis, With Saakshi Khattri, MD

Oral options for plaque psoriasis are expanding rapidly. The US Food and Drug Administration (FDA) approved icotrokinra (Icotyde), the first oral interleukin-23 receptor antagonist, in March 2026, and phase 3 data on the TYK2 inhibitors zasocitinib and envudeucitinib now show skin-clearance rates approaching those of injectable biologics.

Saakshi Khattri, MD, associate professor of dermatology at the Icahn School of Medicine at Mount Sinai, spoke with HCPLive about these developments in the psoriasis space, discussing the shift during Psoriasis Awareness and Action Month, observed each August.

At the 2026 American Academy of Dermatology (AAD) Annual Meeting, investigators presented phase 3 findings from the TOGETHER-PsA trial (NCT06588296), pairing tirzepatide (Zepbound) with ixekizumab (Taltz) in patients with psoriatic arthritis and obesity or overweight status. The trial adds randomized evidence to a combination strategy already used selectively in psoriatic arthritis clinics.

"We know psoriasis, psoriatic arthritis patients have metabolic syndrome, and they tend to have a high BMI, and there's data to support that patients with a higher BMI necessarily don't respond as robustly to systemic options that we have, or they are more recalcitrant to options that would otherwise work for somebody that has a lower BMI," Khattri said.

Among 271 adults with active psoriatic arthritis and a body mass index of 27 kg/m² or higher, 31.7% on combination therapy achieved simultaneous ACR50 response and at least 10% weight loss at week 36, compared with 0.8% on ixekizumab alone (P < .001). ACR50 alone was reached by 33.5% of the combination group versus 20.4% with monotherapy (P = .02). Khattri said more of her patients now request combination therapy, and she advocates for adding a weight-loss medication when patients meet BMI and comorbidity criteria.

In the phase 3 LATITUDE PsO 3001 and 3002 trials (NCT06088043, NCT06108544), zasocitinib produced a 90% reduction in Psoriasis Area and Severity Index score (PASI 90) in 61.3% and 51.9% of patients at week 16, versus 16.8% and 15.9% with apremilast. Envudeucitinib (ESK-001), studied in the ONWARD1 and ONWARD2 trials (NCT06586112, NCT06588738), reached roughly 65% PASI 90 and 40% complete clearance by week 24. Icotrokinra's pivotal program reported about 65% of patients reaching clear or almost-clear skin and 50% reaching PASI 90 at week 16.

Editor's Note: This transcript has been edited for grammar and clarity using artificial intelligence tools. Khattri’s relevant financial disclosures include LEO Pharma, Galderma, Eli Lilly, and Johnson & Johnson.

References

1. Takeda Pharmaceuticals. Zasocitinib delivered rapid and durable skin clearance in phase 3 trials (LATITUDE PsO 3001/3002, NCT06088043, NCT06108544). 2026.

2. Johnson & Johnson. FDA approval of ICOTYDE (icotrokinra) ushers in new era for first-line systemic treatment of plaque psoriasis. March 18, 2026.

3. Dermatology Times. Phase 3 ONWARD data position envudeucitinib as high-efficacy oral TYK2 inhibitor in psoriasis (ONWARD1/ONWARD2, NCT06586112, NCT06588738). 2026.

4. Merola J. TOGETHER-PsA: Ixekizumab + Tirzepatide Deliver Superior Efficacy Over Biologic Monotherapy, With Joseph Merola, MD. Rheumatology Live. August 27, 2026. https://www.rheum-live.com/view/together-psa-ixekizumab-tirzepatide-deliver-superior-efficacy-over-biologic-monotherapy-with-joseph-merola-md.