Tirzepatide Plus Ixekizumab for Psoriasis and Psoriatic Arthritis: The TOGETHER Trials

Adding tirzepatide to ixekizumab (Taltz) beat ixekizumab alone in two randomized phase 3b trials, but most of the gap came from weight, with a smaller gain on the skin or joints themselves. In TOGETHER-PsO, 40.6% vs 29.0% of adults with psoriasis and overweight or obesity reached completely clear skin (PASI 100) at week 36^[1]. In TOGETHER-PsA, 33.5% vs 20.4% of adults with psoriatic arthritis reached a 50% joint-score improvement (ACR50)^[2]. Both trials were open label, with masked assessors for skin and joint exams, and sponsored by Eli Lilly, which makes both drugs^[1][2][3][4].

What the two trials tested

The designs match closely. Each randomized adults 1:1 to ixekizumab plus tirzepatide or ixekizumab alone, with diet and exercise counseling in both arms, and each required a BMI of 30 or higher, or 27 to under 30 with a weight-related condition^[1][2]. Tirzepatide started at 2.5 mg weekly and rose by 2.5 mg every 4 weeks to the highest tolerated dose of 5, 10, or 15 mg by week 32^[1][2]. Among participants with dosing data, 83.9% in TOGETHER-PsO and 78.9% in TOGETHER-PsA reached 15 mg^[1][2].

TOGETHER-PsO randomized 274 adults at 72 US sites, with a mean BMI of 39.2 and a mean PASI of 19.7^[1]. TOGETHER-PsA analyzed 271 adults in the US and Puerto Rico, with a mean BMI of 37.6; 69.7% were women and 63.1% had already used an advanced therapy^[2]. Both trials run 52 weeks, but these reports stop at the week 36 primary endpoint^[1][2]. People with earlier failure of or intolerance to an IL-17 inhibitor or a GLP-1 drug were excluded, as was anyone who had used either study drug before^[1][2].

Results at week 36

The table lists primary and selected secondary results from both papers^[1][2]. Primary and key secondary endpoints were adjusted for multiple testing. The others carry nominal P values only and should be read as supporting evidence^[1][2].

Why the headline endpoint flatters the combination

Both primary endpoints required a disease response and at least 10% weight loss in the same person. Ixekizumab alone has little effect on weight, so that arm had almost no way to win: only 9.1% and 4.5% reached the weight threshold^[1][2]. Compare the differences. In psoriasis the gap was 21.2 percentage points on the composite and 11.6 on PASI 100 alone. In psoriatic arthritis it was 30.9 on the composite and 13.1 on ACR50 alone^[1][2]. A composite like this is a fair test of treating both conditions at once, and a poor measure of how much more the skin or joints improved.

The disease-only results deserve a closer look. The lower bound for PASI 100 was just 0.3 points above zero, and PASI 75 and PASI 90 did not separate significantly, partly because ixekizumab alone already performed well^[1]. In TOGETHER-PsA, patient-rated arthritis pain did not differ between arms (−25.3 vs −21.9 points, P = 0.217), while function, fatigue, and C-reactive protein favored the combination on nominal testing^[2]. Letters to the journal have since questioned the psoriatic arthritis trial, one under the title “When the endpoint decides the winner”^[6]. Those letters have no published abstract, so their arguments are not summarized here.

Is it the weight loss or something else?

Neither trial can say, because neither had a tirzepatide-only arm^[1][2]. The TOGETHER-PsO authors state that further work is needed to determine how much of the skin benefit followed weight change^[1]. The TOGETHER-PsA authors point to an ACR50 difference as early as week 4, before meaningful weight loss, as suggesting a benefit independent of weight, but that result is nominal and comes from an open-label trial in which participants knew their treatment^[2]. The TOGETHER-PsO authors list a related limit for their own trial: masked assessors may have inferred treatment from weight change^[1].

A third explanation is drug exposure. The Taltz label states that “Ixekizumab clearance and volume of distribution increase as body weight increases”^[3], so losing weight could plausibly change how much drug reaches its target. The main papers report no ixekizumab drug levels, and a published letter frames the same question in its title: “Weight, pharmacokinetics, or cytokines?”^[7]. The direct-effect idea also has a contrary data point. In a small 8-week placebo-controlled trial in glucose-tolerant patients, liraglutide produced weight loss without a significant PASI change, a different and much shorter experiment, which our review of semaglutide and psoriasis evidence covers in more depth^[8]. One 2026 review treats TOGETHER-PsA as proof of concept and calls extrapolation to other inflammatory diseases hypothesis-generating^[9].

Safety through the data cutoff

Gastrointestinal effects drove the difference, as expected with tirzepatide, and the TOGETHER-PsO authors report that they generally improved over time^[1]. Serious adverse events were no more common with the combination in either trial, though these studies were small and short for judging rare events^[1][2].

No deaths occurred in either trial^[1][2]. In the TOGETHER-PsO combination arm, individual cases included necrotizing fasciitis, optic ischemic neuropathy in a participant with multiple predisposing risk factors, and suspected pancreatitis, each in one person^[1]. Single events like these cannot establish or exclude a link to treatment. Infections were reported about as often in each arm: 26.8% vs 29.9% in TOGETHER-PsO and 37.0% vs 37.1% in TOGETHER-PsA^[1][2].

What the non-randomized reports add

• Low-dose tirzepatide on ixekizumab. A prospective single-arm study followed 64 adults on stable ixekizumab who added tirzepatide titrated to 5 mg. At week 24, weight fell 10% and PASI went from 4.2 to 1.01, with no control group^[10].
• Tirzepatide started alongside a biologic. In a propensity-matched study of psoriatic arthritis, 31 tirzepatide patients were compared with 62 controls. An acceptable symptom state on the PsAID-12 questionnaire was reached by 48% vs 21% at 6 months, an association that may reflect who was offered the drug^[11].
• Flares are reported too. A 2026 systematic review of 26 studies, mostly case reports and small observational work, found improvements across several drugs alongside reports of paradoxical eruptions and exacerbations^[12]. One case describes a 37-year-old in remission whose psoriasis flared about 4 weeks after starting tirzepatide; a single case cannot show the drug caused it^[13].

Where this leaves patients

Taltz is indicated for moderate-to-severe plaque psoriasis in patients 6 and older and for active psoriatic arthritis in adults^[3]. The Zepbound label revised in August 2026 lists long-term weight reduction in adults with obesity or with overweight plus a weight-related condition, and moderate to severe obstructive sleep apnea in adults with obesity; psoriatic disease is not among its indications^[4]. In practice, the trials speak to people who already qualify for both drugs. They do not support tirzepatide as a psoriasis treatment for someone under the trials’ BMI range, and they say nothing about tirzepatide without a biologic.

The weight figures may not be final either, since some participants reached their top dose only by week 32, while the SURMOUNT-1 obesity trial measured its primary result at week 72^[1][5]. Whether the skin and joint gaps hold or widen depends on 52-week data not yet reported in these papers. Separate ongoing trials are studying adding tirzepatide in people with an inadequate IL-17 response, the group excluded here^[1][2]. For the wider question of combining incretin drugs with other biologics, see our guide to GLP-1s alongside psoriasis and eczema biologics, a question these two trials do not answer.

Points worth raising with a dermatologist or rheumatologist:

• Whether your current skin or joint control leaves room for improvement, since ixekizumab alone already reached PASI 75 in 87.2% of TOGETHER-PsO participants^[1].
• Whether you qualify for tirzepatide on weight or sleep apnea grounds, and who will manage titration and gastrointestinal side effects.
• Whether results apply if you use a different biologic. These trials tested ixekizumab only^[1][2].