Bringing TOGETHER-PsA Into Clinical Practice Save

When Ms. RS came into my clinic for a new patient evaluation, she was suffering from highly active skin disease, joint swelling, pain and poor mobility. She had widely present cutaneous psoriasis covering about 15% of her body surface area. Her joints were painful and swollen, and she reported hours of stiffness in the morning. Her psoriatic arthritis affected her spine, nails, and heels. As I addressed her new diagnosis of psoriatic arthritis, I told her that initiating immunosuppressive therapy was only part of a comprehensive treatment strategy. Her body mass index was 46, indicating class III obesity. A treatment plan focused solely on her inflammatory disease without addressing her weight would not fully address her overall disease burden.

Ms. RS reported that she was well aware that her obesity was impacting her health, and likely her joint pain. She did not, however, realize that inflammatory arthritis and skin psoriasis were associated with obesity. She had considered medication therapy for weight loss but was nervous about starting injectable GLP-1 medications. I counseled her on the complex relationship between obesity and autoimmune disease activity. Additionally, we discussed that inflammatory disease is associated with increased cardiovascular disease and addressing her co-morbidities is important in maintaining her long-term health. We discussed recommended biologic treatment options for her severe disease, most of which were injectable medications. My nursing staff walked through the administration of injection therapies, easing her fears of large needles and painful injections.

As we discussed biologic therapy in psoriatic arthritis, I presented the novel data from the TOGETHER-PsA trial. We talked about the open-label trial evaluating the efficacy and safety of combining ixekizumab (IXE) and tirzepatide (TZP). In this study by Joseph Merola, MD and colleagues, 271 overweight or obese study participants were randomized to IXE+TZP versus IXE alone in treatment of psoriatic arthritis. Patients on combination therapy met the primary endpoint of simultaneous achievement of ACR50 response and 10% weight reduction at 36 weeks at 31.7%, versus 0.8% in the monotherapy IXE arm. These differences were not only explained by weight loss as ACR50 responses were met in 33.5% of patients on combination therapy versus 20.4% with ixekizumab alone.

When I described the connection between inflammatory arthritis, psoriasis and obesity, Ms. RS was motivated to address both issues. 

While not every patient or clinician wants to start two therapies simultaneously, this was an opportunity to address two diseases in severe need of optimization. Upon reviewing various possible biologic therapies, Ms. RS was most impressed at the available data for ixekizumab with GLP-inhibitor. This therapy also offered the potential to address her axial, nail and entheseal domains. I reached out to her primary care physician, who had been offering GLP-1 inhibitors for several visits, and reported her interest in initiation. Other patients may benefit from other biologic or GLP-1 inhibitor therapies than the two study drugs in the TOGETHER-PsA study, but this trial provides evidence supporting an approach that can simultaneously address inflammatory disease and excess weight. Further studies will be needed to understand the generalizability of biologic and GLP therapies on other rheumatic conditions and other medication therapies.

At our follow-up in 3 months, Ms. RS had significant improvement with both therapies. She noted mild gastrointestinal intolerance with tirzepatide but had acheived PASI90 and ACR70 responses. She had lost an initial 7 pounds and planned continued dose escalation of tirzepatide with the goal of achieving greater weight reduction over time. Ms. RS’s experience highlights that controlling inflammation is essential but may not address the full burden of disease in patients with concomitant obesity. The TOGETHER-PsA trial provides prospective evidence supporting an integrated approach to PsA and weight management, reinforcing the importance of addressing both inflammatory disease activity and metabolic health as part of comprehensive, patient-centered rheumatologic care.