Another frontier of GLP-1 therapy could be opening up. Clinical trial data out today finds that tirzepatide (the active ingredient in the GLP-1 weight loss drug Zepbound) can be an effective add-on treatment for psoriatic arthritis.
On Friday morning, Eli Lilly released data from its Phase 3b trial testing tirzepatide 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 performed significantly better at reducing arthritis symptoms than Taltz alone, researchers found. People taking tirzepatide also lost substantial weight.
“These results demonstrate how an integrated treatment approach has the potential to improve the standard of care in a compelling and comprehensive way,” said Mark Genovese, senior vice president of Lilly Immunology development, in a statement from the company.
Two better than one
Psoriatic arthritis is a chronic form of arthritis, or joint inflammation, associated with the skin disorder psoriasis. Both conditions are caused by the immune system misfiring and wrongly attacking the body itself (the skin and joints in particular). About a quarter of people with psoriasis will also have psoriatic arthritis.
Symptoms of these conditions can vary in severity but often appear as flare-ups that can be triggered by various factors. Though there is no cure for either, people can manage or reduce their flare-ups through medications and the avoidance of known triggers.
While people with a family history of psoriasis are noticeably more likely to have it themselves, the environment also seems to play an important role. Studies have suggested that obesity can raise the risk of developing psoriasis, worsen a person’s existing illness, and even reduce the effectiveness of treatments. Rates of obesity also seem to be higher in people with psoriasis than the general public.
This reality has led to speculation that treating someone’s obesity at the same time as their psoriasis/psoriatic arthritis can improve outcomes for both. According to Eli Lilly, however, theirs is the first-ever controlled clinical trial to explicitly test that hypothesis.
The TOGETHER-PsA trial included 271 people who were overweight or obese and had active psoriatic arthritis. Half were randomized to only receive 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 met its primary goal. About a third of patients experienced a 50% or greater reduction in their arthritis symptoms and at least 10% weight loss, compared to 0.8% of patients in the Taltz-only group. 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 64% improvement.
“The observed benefit with treatment using Taltz and Zepbound appears to meaningfully impact psoriatic disease activity, indicating that for many patients, PsA is an obesity-related condition,” said Joseph Merola, chair of dermatology and professor of rheumatology at the University of Texas Southwestern, in a statement from Lilly.
What happens now?
GLP-1 drugs have significantly improved obesity treatment in recent years, and tirzepatide seems to be the most effective option currently available. In clinical trials, the drug—which mimics GLP-1 and another hunger-related hormone, GIP—has directly outperformed 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 strongly linked to obesity). The company plans to release results later this year of a separate trial testing Zepbound plus Taltz for people with moderate-to-severe plaque psoriasis and obesity.
All these findings will have to be vetted through the typical peer-review and regulatory process. But assuming this research passes muster, it could certainly change the typical regimen prescribed to people with psoriatic arthritis and psoriasis.
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