DENVER – A phase III randomized trial has shown that adding a GLP-1 agonist to psoriasis medication significantly improves outcomes in patients with psoriatic arthritis (PsA) and who are overweight or obese.
After 36 weeks, about a third of patients taking ixekizumab (Taltz) and tirazepate (Zepbound) had at least a 50% improvement in psoriatic arthritis status (ACR50) and a 10% weight loss. In contrast, less than 1% of patients treated with ixekizumab alone met the composite endpoint. Significantly more patients treated with both drugs achieved ACR50 status, at least 10% weight loss, or ACR20 plus at least 5% weight loss.
Joseph F., MD, of UT Southwestern Medical Center in Dallas, at the American Academy of Dermatology meeting. Merola reported that other arthritis-related endpoints supported the combination, as did patient-reported outcomes (PROs).
“I think the early separation and statistical separation of ACR50 was really important,” Merola said. “To me, this represents a paradigm shift because we think about how other combination therapies have not made a huge dent in our ability to move ACR50 and other endpoints. We are now seeing clear improvements, and I really believe that helping our patients cope with this major co-morbidity of the disease will dramatically improve quality of life over time and dramatically improve survival among these patients.”
During a discussion after the presentation, Merola was asked if there was more ixekizumab available to patients who had lost weight.
“We know that when people lose weight, the drug probably has a better effect on these patients,” Merola said. “I would argue that in the short term, for whatever reason, they are seeing benefits, and I’m excited about that. I think the other piece that I’m quite excited about, which we don’t have here but is coming, is some therapeutic benefits, which I have no doubt you’ll be excited to see as well.”
He said a mechanistic study is ongoing in an effort to better understand the factors involved in the improved outcomes seen with the combination.
The therapeutic potential of GLP-1 agonists has increasingly attracted the interest of physicians and researchers in psoriatic disease. In the 2024 meeting of Group for Research and Evaluation of Psoriasis and Psoriatic ArthritisA keynote address focused on the therapeutic potential of GLP-1 agonists, acknowledging the lack of direct evidence linking the drug class to psoriatic disease and calling for more study.
A Recent Review Articles Provided an update on GLP-1 agonists for rheumatology specialists. National Psoriasis Foundation Recently added information about GLP-1 agonists for physicians and patients to its website. International Psoriasis Council The website also contains information about the therapeutic potential of GLP-1 agonists in psoriasis.
Despite the lack of strong evidence, there is a strong rationale for interest in GLP-1 agonists in psoriatic disease, based on the drugs’ proven effects on obesity and metabolic syndrome, two common comorbidities of patients with psoriasis and psoriatic arthritis. A Recent Retrospective Chart Review Of 1,500 patients with psoriasis or hidradenitis suppurativa, 60% were eligible for the use of GLP-1 agonists.
overweight and obesity Merola reported that the joint affects 70-80% of PsA patients. What is obesity related to? Worse results in PSA, And patients with PsA are more likely to have cardiovascular comorbidities.
Due to the feasibility of combined therapy studied together, two phase III trials evaluated ixekizumab with or without tirazepide, one for PSA and for the other Psoriasis (PSO). Results of the psoriasis study will be reported later, Merola said.
In Together-PSA, investigators enrolled patients with active PSA and who had obesity (body mass index (BMI) ≥30) or overweight (BMI ≥27 to <30) and at least one weight-related comorbidity. They were randomized to ixekizumab with or without tirazepate, and the primary endpoint was the composite of ACR50 and ≥10% weight loss at week 36.
Data analysis included 271 patients whose mean age was 55 years and mean BMI was 37.6. The study population was 70% female, and 63% of patients received advanced therapy.
The 36-week results showed that 31.7% of the combination arm met the composite endpoint, compared to 0.8% of the ixekizumab group (P<0.001). The combination provided a significant benefit for key secondary endpoints:
- ACR50: 33.5% vs 20.4%, P<0.05
- ACR 20 and ≥5% weight loss: 69.7% vs 10.3%, P<0.001
- ≥10 weight loss: 84.5% vs 4.5%, P<0.001
Patients in the combination arm lost an average of 18.0% of baseline body weight, while patients on ixekizumab alone lost 1.1%. There was a significant improvement in PRO with the combination (P<0.05 se P<0.001).
The combination therapy was generally well tolerated, Merola said. No serious or unexpected events occurred and the most common events were of a gastrointestinal nature as expected.
Preliminary (36-week) data for the TOGETHER-PSO trial, which included patients with moderate/severe PSO, showed that more patients treated with the combination achieved Psoriasis Activity and Severity Index (PASI) goals, including PASI 75, PASI 90, and PASI 100.
