Philip J. Mease, MD

Targeting Cardiometabolic Burden in PsA, With Philip Mease, MD

Growing attention has turned toward the role of obesity, metabolic dysfunction, and cardiovascular risk in shaping psoriatic arthritis (PsA) outcomes. Rheumatologists increasingly recognize that excess adiposity not only elevates systemic inflammation but also reduces the likelihood of achieving key treatment Recent clinical interest has expanded to include GLP-1 receptor agonists and dual GLP-1/GIP agonists, further expanding the investigative frontiers for the in-demand drugs.

Emerging evidence suggests that GLP-1–based therapies may influence immune cell activity, reduce adipose-derived cytokines, and mitigate obesity-driven inflammatory load. Several studies presented at the 

American College of Rheumatology (ACR) Convergence 2025

, held October 24–29 in Chicago, Illinois, explore GLP-1s in a variety of rheumatological diseases and others examine more closely cardiometabolic outcomes 

Philip Mease, MD, Clinical Professor at the University of Washington and Director of Rheumatology Research at the Swedish Medical Center in Seattle, presented a new analysis of apremilast, which seemed to exert beneficial cardiometabolic effects. In the phase 4 FOREMOST trial, patients with early oligoarticular PsA randomized to APR experienced greater reductions in BMI (–1.77% vs 0.21%) and weight (–1.71% vs 0.25%) at Week 16 compared with placebo. These improvements were maintained through 48 weeks, with over 50% of treated patients achieving ≥1% weight loss and approximately 20% achieving ≥5% reductions. Patients also demonstrated a shift toward lower-risk BMI and HbA1c categories over 48 weeks, with the largest improvements occurring in those who began the study with obesity or diabetes.

Another abstract reported that PsA patients receiving GLP-1 receptor agonists exhibited lower risk of major adverse cardiac events and reduced mortality compared with PsA patients not using GLP-1 RAs, indicating potential cardioprotective and anti-inflammatory advantages. These findings support the concept that GLP-1 RAs may serve as a meaningful adjunct for PsA patients who have cardiometabolic comorbidities such as obesity or type 2 diabetes, although additional mechanistic and long-term studies are needed.

"One other area that rheumatologists are becoming increasingly sensitive about is the comorbidities of obesity and cardiovascular issues. This is being highlighted by studies which are showing us that if a patient is obese, their disease activity is greater and they are less likely to achieve targets like remission [and] low disease activity if they are obese," Mease said.

Mease's disclosures include AbbVie, ACELYRIN, Amgen, Bristol Myers Squibb, Century Therapeutics, Cullinan Biotech, Eli Lilly, Genascence, GRAPPA, Immagene, Johnson & Johnson, MoonLake Immunotherapeutics, Novartis, OMERACT, Pfizer, SPARTAN, Takeda, and UCB Pharma.

Mease P, Cantero AG, Soung J, et al. Effects of Apremilast on Body Mass Index, Weight, and HbA1c as Cardiometabolic Outcomes in Patients With Early Oligoarticular Psoriatic Arthritis in the FOREMOST Study. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Abstract #0581

Tsibadze N, Tskhakaia I, Tan I. Mortality and Major Adverse Cardiac Events (MACE) with GLP-1 Receptor Agonists in Psoriatic Arthritis. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Abstract #0849

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Mease discussed the latest updates on apremilast and growing attention to cardiometabolic outcomes at ACR Convergence 2025.

Deucravacitinib, Zasocitinib Validate TYK2 Inhibition in PsA, With Philip Mease, MD

Deucravacitinib has continued to demonstrate efficacy across characteristics of people with psoriatic arthritis (PsA) ahead of its March 6, 2026 Prescription Drug User Fee Act (PDUFA).

Efficacy and safety data for up to 52 weeks from the phase 3 POETYK PsA-1 (NCT04908202) trial were presented at the 

, held October 24–29 in Chicago, Illinois, by Philip Mease, MD, Clinical Professor at the University of Washington and Director of Rheumatology Research at the Swedish Medical Center in Seattle.

In POETYK PsA-1, 670 biologic-naïve patients with active PsA were randomized to deucravacitinib 6 mg daily or placebo for 16 weeks, after which all placebo patients switched to active therapy. The study met its primary endpoint with highly significant ACR20 improvements at Week 16 (

 <.0001), and responses continued to deepen through Week 52. The detailed efficacy table shows that at Week 16, PASI75 responses reached 51.9% with deucravacitinib vs 7.1% with placebo (95% CI 43.9–59.8 vs 3.7–12.0). MDA response rates were 19.0% vs 10.2%. DAS28-CRP improved with an adjusted mean change of –1.33 vs –0.83. Patient-reported outcomes meaningfully favored deucravacitinib, including HAQ-DI (–0.39 vs –0.22), SF-36 PCS (+6.05 vs +3.71), and FACIT-Fatigue (+4.6 vs +2.0). Extra-articular manifestations also improved, with pooled LEI enthesitis resolution of 50.3% vs 45.1% at Week 16.

By Week 52, patients who switched from placebo achieved comparable outcomes, including PASI75 ~51.8% after switching and 66.0% in continuously treated patients. Radiographic non-progression remained high (82.0% after switching; 73.3% continuous). Safety remained favorable without new MACE, VTE, or opportunistic infection signals.

during the conference to discuss updated results from the phase 3 POETYK PsA-1 trial. He highlighted how these data, along with emerging TYK2 candidates such as zasocitinib, are shaping the future therapeutic landscape.

He touched on emerging phase 2b data for zasocitinib (TAK-279), which demonstrated robust PASI75 responses across patient subgroups, including rates up to 78–93% in certain baseline strata, supporting the growing momentum behind next-generation TYK2 inhibitors.

"It's a good time for us in psoriatic practice, because of the availability of medicines with different mechanisms of action and good quality results to treat our patients," Mease said.

van der Heijde D, Mease P, Paul C, et al. Efficacy and Safety of Deucravacitinib up to Week 52: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study in Patients With Active Psoriatic Arthritis Who Are Naive to Biologic Disease-Modifying Antirheumatic Drugs. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Abstract #LB20

Johnson V. TYK2 Inhibitor Deucravacitinib up for FDA Review for Psoriatic Arthritis. Article. HCPLive. July 21, 2025. https://www.hcplive.com/view/tyk2-inhibitor-deucravacitinib-up-for-fda-review-for-psoriatic-arthritis

Elbuluk N, Gooderham MJ, Blau J, et al. Zasocitinib (TAK-279), an Investigational, Oral, Allosteric, Selective TYK2 Inhibitor, in Moderate-to-Severe Plaque Psoriasis: Efficacy Analysis by Baseline Characteristics from a Randomized Phase 2b Trial. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Abstract #1155


Mease discussed the latest updates on deucravacitinib and zasocitinib at ACR Convergence 2025.

Achieving “State Zero”: New Data on Bimekizumab, Other IL-17is, Transform PsA Treatment Goals, with Philip Mease, MD

Interleukin-17 (IL-17) inhibition continues to evolve as a major frontier in psoriatic arthritis (PsA) treatment, with new data on both approved and investigational therapies recently presented at the 

Mease spoke about key findings on several IL-17 targeting agents, bimekizumab, sonelokimab, and izokibep, that are shaping current and future management strategies for PsA. 

New data on bimekizumab, a dual IL-17a/17f inhibitor, reinforce the importance of achieving complete remission across clinical domains, or "state zero." Mease and colleagues found that when patients reach “state zero”—meaning full resolution of manifestations such as swollen joints, enthesitis, or radiographic progression—they experience substantial parallel improvements in pain, function, and overall quality of life. 

Meanwhile, new phase 2 data on sonelokimab, a nanobody IL-17A and IL-17F inhibitor, demonstrated that at 24 weeks, more than half of treated patients achieved major composite outcomes such as ACR50 and minimal disease activity, with responses spanning key domains of arthritis, enthesitis, and skin involvement.

Lastly, Mease discussed 1-year outcomes from izokibep, a small molecule IL-17A inhibitor with a compact protein scaffold design, which demonstrated durable efficacy through 52 weeks. Patients maintained high rates of ACR50 responses, functional improvement, and sustained low disease activity, suggesting that next-generation small molecule constructs may rival biologics in depth and durability of response.

"There's a correlation with improvements in other important areas for patients, really low states of pain, improvement in function, quality of life. And so it just reinforces the message that what we're trying to get to in a disease is complex," Mease said.

Mease PJ, Poddubnyy D, Bajracharya R, et al. Long-Term Safety and Tolerability of Bimekizumab Treatment Across Phase 2b and Phase 3 Studies in Patients with Axial Spondyloarthritis or Psoriatic Arthritis: 3-Year Update from the Phase 3 Studies. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Poster #1454

Mease PJ, Gossec L, Deodhar A, et al. Sonelokimab in Patients With Active Psoriatic Arthritis Who Are Naive to Biologic DMARDs: Phase 2 ARGO Analysis and Phase 3 IZAR-1 Study Design. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Poster #1455

Mease PJ, Behrens F, Kivitz AJ, et al. Efficacy and Safety of Izokibep, a Novel IL-17A Inhibitor, in Patients with Active Psoriatic Arthritis: Week 52 Results from a Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase 2b/3 Study. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Poster #LB08

Mease discussed the latest updates on bimekizumab, sonelokimab, and izokibep at ACR Convergence 2025.

On August 15, 2025, the US Food and Drug Administration (FDA) approved TNX-102 SL under the name Tonmya, marking the 

first new fibromyalgia therapy in over 15 years

. Developed by Tonix Pharmaceuticals, TNX-102 SL is a sublingual formulation of cyclobenzaprine and the first member of a new class of non-opioid analgesics for the condition. Its approval represents a pivotal step forward for millions of patients living with chronic, often debilitating pain, fatigue, and nonrestorative sleep.

The FDA decision was supported by phase 3 RESILIENT trial data, which demonstrated significant reductions in daily pain scores as early as week 1, sustained through week 14 (

 <.0001). Patients on TNX-102 SL also experienced improvements in sleep disturbance, fatigue, and overall sleep quality, with effect sizes ranging from 0.32–0.50. Importantly, the therapy showed a tolerable safety profile, with discontinuations due to adverse events occurring in just 6.1% of treated patients.

In this Q&A, Philip Mease, MD, director of Rheumatology Research at Providence Swedish Medical Center and clinical professor at the University of Washington School of Medicine, shared insights on how TNX-102 SL may reshape fibromyalgia care, its unique mechanism targeting sleep-related symptoms, and the broader implications for treating nociplastic pain.

How do you anticipate integrating TNX-102 SL into current treatment paradigms for fibromyalgia? 

Assuming that the cost to the patient will not be exorbitant, assuming insurance coverage, and that there will be a reasonably non-onerous prior authorization process, we do plan to prescribe TNX-102 SL in our practice, based on the efficacy and safety data demonstrated in the phase 3 trials. I am aware that some rheumatologists have commented that it will just be an expensive version of generic, oral cyclobenzaprine, but the fact that it was able to show statistical separation from placebo and has a unique mechanism of action that yields more enduring effect during the nighttime’s sleep cycles, and that its bioavailability is greater, all add up to our wanting to use it. Many rheumatologists prefer not to see fibromyalgia patients for whom that is the primary diagnosis, because of their complexity, but since fibromyalgia is a concomitant condition in up to 20% of most rheumatologic conditions, rheumatologists end up managing the condition quite frequently. Since patients may not have had success, or have lost effect from previously tried approved FM medications, such as duloxetine, I would expect clinicians to reach for a newly approved treatment, again assuming the prior authorization is not too onerous. 

How does TNX-102 SL’s sublingual cyclobenzaprine formulation targeting nonrestorative sleep differs from previous therapies, and why does this matter for treating core fibromyalgia symptoms? 

A core symptom and sign of FM is disturbance in sleep physiology, as shown so well by the late Harvey Modolfsky at the University of Toronto. Tonmya has similar biology as the older treatments such as the tricyclic, amitriptyline, which has overlapping mechanistic features with generic cyclobenzaprine and TNX-102 SL. TNX-102 SL appears to have some superior effect to generic cyclobenzaprine in more enduring effect during the full night time sleep cycle, peaking at 5 hours into sleep, and not having residual effect during the day. Another feature is that there is less of the metabolite, norcyclobenzaprine, that has a longer half life than cyclobenzaprine, competes for the same receptors as cyclobenzaprine, and has a lesser effect.

TNX-102 SL is a first-in-class, non-opioid approach in fibromyalgia— what further potential do you think this type of drug has in the field? 

Many rheumatologic patients have “residual” pain even when immunomodulatory drugs demonstrate good effect on signs of inflammation. Much of this could be due to central sensitization. To the extent that sleep disturbance is part of the central sensitization phenomenon, then TNX-102 SL could be used concomitantly to try to reduce residual pain.

What further research are you looking forward to with TNX-102 SL?

 I look forward to seeing RWE from long term clinical registries, to see if addition of this medication makes a difference, in settings not as controlled as clinical trials, with even more complex patients, there is improvement of pain, fatigue, and sleep disturbance. [In terms of other investigations with] long COVID and PTSD... there is overlapping pathophysiology with FM, including features of pain, fatigue and sleep disturbance, so I think it is worthwhile to consider use of this drug in these and other conditions that are at least partially characterized as central sensitization.

Given the complexity and heterogeneity of fibromyalgia, what do you think are the most pressing unmet needs that remain in the field past this approval? 

One of the big issues we are addressing in the OMERACT chronic pain working group, which I help co-chair, is education of clinicians, and patients, that pain is complex and often includes the phenomenon of central sensitization. That type of pain is termed “nociplastic” pain. This type of pain may need different approaches to effectively treat. So whilst immunomodulatory medicines may effectively treat inflammation and reduce classic nociceptive pain, adjunctive approaches may be needed to treat nociplastic pain. This may also reduce the tendency to keep changing the patient’s immunomodulatory medicine, if inflammation is well controlled. Along with this education, we are hoping to see measures of nociplastic pain used in clinical trials and in clinical practice to aid clinicians to navigate this complexity.

This transcript has been edited for clarity.

Johnson V. FDA Approves TNX-102 SL, First New Fibromyalgia Therapy in 15 Years. Article. HCPLive. August 15, 2025. https://www.hcplive.com/view/fda-approves-tnx-102-sl-first-new-fibromyalgia-therapy-in-15-years

Articles

Mease discussed his hopes for the new approval's impact on the fibromyalgia field.