ZEPBOUND + TALTZ Improves Psoriatic Arthritis Symptoms in Phase 3b Trial!

New trial data!

Original posted at obesity.news/ on Jan 8, 2026

As Eli Lilly continues to explore how incretin therapies might extend beyond obesity and diabetes, the company is increasingly testing their role in diseases where inflammation and metabolic dysfunction intersect.

In topline results released Thursday, Lilly said its Phase 3b TOGETHER PsA study showed that combining its IL 17A biologic Taltz with its obesity drug Zepbound led to meaningfully better arthritis outcomes than Taltz alone.

The company framed the data as evidence that obesity is not just a comorbidity in psoriatic arthritis, but a modifier of disease activity.

The numbers suggest that framing may be justified.

WATCH THE VIDEO:

TOGETHER PsA enrolled 271 adults with active psoriatic arthritis and obesity or overweight. Participants were randomized to receive either Taltz alone or Taltz plus Zepbound, both administered subcutaneously.

The primary endpoint was deliberately stringent. Patients had to achieve both a 50% improvement in psoriatic arthritis activity, measured by ACR50, and at least 10% weight loss by week 36.

Nearly 32 percent of patients in the combination arm met that composite endpoint. Fewer than 1% of patients receiving Taltz monotherapy did.

That difference was statistically significant by a wide margin.

On a more conventional measure, ACR50 alone, the combination arm still outperformed. About 34% of patients receiving both therapies achieved ACR50, compared with roughly 20% of patients on Taltz alone, representing a 64% relativeincrease.

The study population was not treatment naive. Average BMI at baseline was 37.6. More than 60% of participants had prior exposure to advanced therapies. Disease activity and functional impairment scores reflected a high burden population.

Obesity as a Lever, Not a Background Variable

Lilly’s messaging throughout the release was consistent.

The company did not frame the results as weight loss improving comfort, adherence, or quality of life. Instead, it framed obesity treatment as directly reducing inflammatory burden and enabling better disease control.

That distinction matters.

Clinical guidelines for psoriatic arthritis already recommend addressing obesity. What they do not show is what happens when obesity is treated pharmacologically alongside biologic therapy in a controlled trial.

TOGETHER PsA was designed to answer that question.

One investigator suggested the data indicate psoriatic arthritis may be obesity related in a meaningful subset of patients, a framing that challenges the way inflammatory diseases are typically siloed in practice.

If that interpretation holds, it could help explain why response rates plateau even as newer biologics target inflammation more precisely.

Subscribe

Safety Was Predictable, Which Strengthens the Signal

Adverse events in the combination arm were largely consistent with the known profiles of Taltz and Zepbound.

Gastrointestinal events were more common among patients receiving Zepbound. Injection site reactions and upper respiratory infections were more common in the monotherapy arm.

No new safety signals emerged, and there were no obvious tolerability tradeoffs that would complicate use of the combination in practice.

That matters because combination strategies often fail not on efficacy, but on tolerability.

Part of a Broader Incretin Strategy

Lilly emphasized that TOGETHER PsA is not a standalone experiment.

A parallel trial in plaque psoriasis is already underway, with topline results expected in the first half of this year. The company positioned the study as part of a broader effort to evaluate whether metabolic intervention can amplify outcomes across immune mediated diseases.

If successful, that approach could support a new category of combination strategies pairing incretin therapies with immune targeted drugs.

What This Likely Means for Patients

For patients, the TOGETHER PsA data reframes a familiar experience.

Many people with psoriatic arthritis cycle through biologics that partially work, plateau, or fail to deliver the response seen in trials. When that happens, the assumption is often immunologic failure, the wrong target, or disease that is simply difficult to control.

This study suggests another explanation.

In patients with obesity, untreated metabolic dysfunction may be limiting how much benefit biologics can provide in the first place.

The results do not suggest that weight loss alone treats psoriatic arthritis. They suggest that addressing obesity alongside immune mediated disease can raise the ceiling of response, even in patients with longstanding disease and prior biologic exposure.

That distinction matters for patients who have been labeled partial responders or non responders without a clear reason why.

It also matters for patients who have repeatedly been told that weight loss is important, without being offered effective tools to achieve it.

Practically, the data support a more integrated approach to care. One where obesity is treated as a modifiable driver of disease activity rather than a background risk factor. One where metabolic therapy is not deferred until other options fail.

For patients, that could translate into fewer therapy switches, better symptom control, and a clearer understanding of why some treatments work better when the full disease burden is addressed.

The data will not change guidelines overnight. Coverage barriers remain. Mechanistic questions remain.

But the signal is clear.

When obesity is treated seriously, inflammatory disease may become easier to control.

And for patients who have lived in the gap between those two realities, that may be the most important takeaway of all.

This article is reader-supported on Substack.

To receive new posts and support my work,

consider becoming a free or paid subscriber.

Subscribe