Adding an Incretin Therapy to a Biologic for PsA: TOGETHER-PsA Trial

Dr. Bakewell describes Together-PsA trial as the first study in rheumatology to examine what happens when an incretin therapy, tirzepatide, is added to a standard biologic, the IL-17A inhibitor ixekizumab. She asks Dr. Perkins why this combination drew research interest and what the results showed. Dr. Perkins calls it one of the field's genuine discovery moments. She describes watching patients who were prescribed incretin drugs for type 2 diabetes or sleep apnea. They unexpectedly showed dramatic improvement in their rheumatologic disease: better joint scores, better skin clearance, and better remission rates than she had seen before. She says rheumatologists around the country began reaching out to drug manufacturers directly. They asked whether a program could be built to make the combination affordable and accessible for patients. The outcomes measured in every clinic visit, joint counts, skin scores, and validated disease-activity indices, were showing meaningfully better results in patients who could access both therapies together.

Dr. Perkins then explains the specific data behind the Together-PsA trial. She says primary outcomes are designed to measure treatments on a level playing field. For this trial, the primary outcomes were ACR50 response and at least 10% body weight reduction. Roughly 30% of patients on the combination of ixekizumab and tirzepatide achieved both endpoints, compared with less than 1% of patients on ixekizumab alone. She calls that 1% figure important context, since those patients likely were also receiving diet and exercise counseling as motivated trial participants. That underscores how much more the added therapy delivers. Secondary endpoints tracked outcomes that matter directly to patients, including skin clearance, itching, fatigue, mental health, and physical function. Dr. Bakewell pushes back on the oversimplified idea that weight is purely calories in versus calories out. She points to genetics, socioeconomic factors, and shift work as variables patients cannot control, which is why having more treatment tools available matters so much.

Kameillia recalls that Dr. Perkins first raised the idea of adding a GLP-class medicine during one of their regular checkups, noticing her ongoing struggles with weight and lingering inflammation. Kameillia says she was initially skeptical, having hoped to manage her weight the old-fashioned way, but trusted Dr. Perkins to explain exactly what the medication would involve. She says Dr. Perkins detailed dosing, walked through the side effects to watch for, and started her at a low dose. Kameillia read on her own as well and kept a journal tracking how she felt as she eased into the medication, cutting back on dairy and certain foods as advised. She reports only mild, occasional stomach upset once she learned what to eat and drink, and otherwise experienced only positive results, with Dr. Perkins monitoring her closely to ensure she lost no more than about two pounds a week. Kameillia says the experience changed her life and that she cannot overstate how amazing she now feels. Dr. Perkins then explains the practical side of prescribing incretin therapy alongside a biologic. She says rheumatologists are not formally trained in obesity medicine, so adopting this approach required real adult learning. She points out that guidelines for these medications suggest visits every 8 to 10 weeks, which lines up well with rheumatology's typical 12-week follow-up schedule. She was motivated to offer the combination herself after watching patients turn major corners in their disease, reasoning that if she did not offer it, someone else should. She notes that the patients enrolled in the Together-PsA trial mirrored Kameillia's profile: people with multiple prior drug failures, rising body weight, and persistently burdensome joint and skin disease despite treatment.

Our next episode, "Mental Health, Comorbidities, and PsA Combination Therapy Trials," widens the lens to the mental health and comorbidity research this combination approach is beginning to touch.