Another frontier for GLP-1 therapy may be opening up. Clinical trial data today finds that tirzepatide (the active ingredient in the GLP-1 weight loss drug Zepbound) can be an effective adjunctive treatment for psoriatic arthritis.
On Friday morning, Eli Lilly released data on Tirzepatide’s Phase 3b trial alongside ixekizumab (pronounced “ix-ee-KIZ-ue-mab”), its approved anti-inflammatory drug. In people with psoriatic arthritis who were overweight or obese, the two-drug combo did much better at reducing arthritis symptoms than Taltz alone, the researchers found. People taking tirzepatide also lost more weight.
“These results show that an integrated treatment approach has the potential to improve the quality of care in a compelling and comprehensive way,” it said. Mark Genovesesenior vice president of Lilly Immunology development, in a statement from the company.
Two are better than one
Psoriatic arthritis is a chronic form of arthritis, or joint inflammation, associated with the skin disease psoriasis. Both conditions are caused by the immune system not working properly and attacking the body inappropriately (especially the skin and joints). About a quarter of people with psoriasis will also have psoriatic arthritis.
The symptoms of these conditions can vary in severity but usually appear as a rash that can be triggered by a variety of factors. Although there is no cure for both, people can control or reduce their breakouts with medication and avoiding known triggers.
Although people with a family history of psoriasis seem more likely to develop it themselves, the environment seems to play an important role. Studies have suggested that obesity can increase the risk of developing psoriasis, worsen a person’s existing illness, and reduce the effectiveness of medications. Obesity rates also appear to be higher in people with psoriasis than in the general population.
This fact has led to speculation that treating obesity at the same time as psoriasis/psoriatic arthritis can improve the outcomes of both. According to Eli Lilly, however, theirs is the first controlled clinical trial to definitively test that idea.
The TOGETHER-PSA trial included 271 people who were overweight or obese and had active psoriatic arthritis. Half were randomized to receive only ixekizumab, an antibody-based drug approved by the FDA to treat psoriatic arthritis in 2017 under the brand name Taltz, and half received Taltz and Zepbound.
By week 36, the trial had reached its primary goal. About a third of the patients experienced a reduction of 50% or more in their arthritis symptoms and at least 10% in body weight, compared to 0.8% of patients in the Taltz group alone. More people in the combination therapy group also experienced a 50% or greater reduction in arthritis symptoms than people taking Taltz alone (33.5% vs. 20.4%). This difference amounted to a relative improvement of 64%.
“The benefit observed with treatment using Taltz and Zepbound appears to have a significant effect on psoriatic disease activity, indicating that for many patients, PsA is a condition related to obesity,” it said. Joseph Merolachairman of dermatology and professor of rheumatology at the University of Texas Southwestern, in a statement from Lilly.
What happens now?
GLP-1 drugs have greatly improved the treatment of obesity in recent years, and tirzepatide appears to be the most effective option currently available. In clinical trials, the drug—which mimics GLP-1 and another hunger-related hormone, GIP—was more effective than semaglutide, the active ingredient in Ozempic and Wegovy.
But Eli Lilly has already expanded Zepbound’s approval beyond treating obesity alone. In late 2024, it received a label extension from the FDA for obstructive sleep apnea (another condition closely related to obesity). The company plans to release results later this year from a separate trial of Zepbound plus Taltz in people with moderate plaque psoriasis and obesity.
All of these findings will need to be evaluated through a standard peer review and regulatory process. But if this study is considered to be very successful, it could change the standard regimen given to people with psoriatic arthritis and psoriasis.
