TOGETHER PsA: Concomitant ixekizumab and tirzepatide in patients with psoriatic arthritis and overweight or obesity

touchIMMUNOLOGY coverage of EULAR 2026

My name is Laura Coates, I’m a rheumatologist and a researcher at the University of Oxford in the UK.

Could you describe the association between PSA and overweight obesity?

We know that patients who are overweight or obese are more likely to develop psoriasis and psoriatic arthritis, and we also see a higher rate of patients being overweight and obese in our psoriatic disease cohort compared to the normal population. It is also crucially associated with poorer outcomes. Patients who are overweight or obese also have more active disease and they don’t respond as well to the therapies that we have available.

What was the rationale for the concomitant administration of ixekizumab and tirzepatide?

We know obesity is a problem and we’ve seen in a couple of previous studies that if patients lose weight their outcomes can improve, so it is a modifiable risk factor. We’ve had studies previously using diet where the weight loss is usually modest and we’ve had studies using shake replacement diets where we get a much bigger weight loss, but patients don’t tend to like them.

With the advent of GLP-1 drugs and combined agonists like tirzepatide, we see a really effective therapy for obesity. The study recruited patients who had active PSA who were starting on treatment with ixekizumab, a proven drug for psoriatic arthritis, but then half of them also got tirzepatide to look at whether the weight loss and or the use of tirzepatide could improve outcomes.

What were the objectives and methodology of the TOGETHER PsA trial?

The key objective was to assess whether weight loss with tirzepatide could improve arthritis outcomes in the TOGETHER PsA trial, and there is also a sister trial looking at improvements in skin outcomes. TOGETHER PsA is a randomized, controlled trial and it is open label; the patients know what they are receiving, but the assessor is blinded.

It is very hard to conduct a blinded study with tirzepatide, because people know whether they are receiving it or not. The study in its totality will last a year, but the primary outcome was at Week 36, when patients had time to get onto a decent dose of tirzepatide and show the weight loss.

What were the primary and secondary endpoints and how well were they achieved?

The primary endpoint was to achieve both ACR50 and a 10% weight reduction and there was a high statistically significant difference at Week 36 between the two groups, which you would expect because ixekizumab doesn’t reduce weight. We weren’t expecting the patients receiving ixekizumab alone to lose weight, but both groups did get some diet and exercise advice, but we know that has limited impact.

The key secondary outcomes were ACR50, which is probably the most interesting to us as rheumatologists, and that had a statistically significant difference in favour of ixekizumab with tirzepatide over ixekizumab alone. The other key secondaries were patients losing 10% weight, very similar to the obesity trials, and that was highly significant with tirzepatide. Then there was a slightly lower bar combination outcome of ACR20 plus 5% body weight loss – a slightly lower response in both arthritis and weight loss – and, again, that had a statistically significant difference in favour of the combined treatment.

How will these findings be used to inform future treatment decisions?

We see a lot of patients who are overweight or obese with PsA, and they experience poorer outcomes with the drugs that we have available. It is important to think about managing obesity well, in order to get the best outcomes out of our arthritis drugs. This study gives us clear evidence of the benefit for joints specifically, while in the sister trial this is shown for psoriasis as well, demonstrating the impact of weight loss directly on disease activity measures and on outcomes.

We also saw that the safety data looked exactly as you would expect for the two separate drugs. There doesn’t seem to be any safety concern or increased safety signals in having both drugs together, which we didn’t know before. I think this gives us strong data to support the use of weight loss medications in patients with psoriatic arthritis. The question now is thinking about how we do that, how we build that into practice, making sure that we have these drugs funded, which is a problem internationally, and thinking about how we combine it with our other treatments for psoriatic arthritis.