TYK2 Inhibition Emerges As A Next-Gen Strategy To Treat PsA

By Shikha Gianchandani, Gaja Gasiorek, and Pooja Goyal, Lifescience Dynamics

The treatment landscape for psoriatic arthritis (PsA) is evolving rapidly, with data presented at EULAR 2025 signaling a potential new chapter in disease management. Unlike traditional Janus Kinase (JAK) inhibitors, Sotyktu (deucravacitinib) offers a different mechanism of action. On June 11, 2025, Bristol Myers Squibb shared Phase 3 trial results for Sotyktu, positioning it as a first-in-class oral selective tyrosine kinase 2 (TYK2) inhibitor for patients inadequately served by traditional biologics and JAK inhibitors.

From TNF Inhibitors to TYK2: An Evolving Treatment Landscape

The early 2000s marked a turning point in the management of PsA, as biologics — most notably TNF-α inhibitors such as Enbrel (Amgen), Humira (AbbVie), and Remicade (Johnson & Johnson) — offered meaningful improvements over conventional therapies. Over the past decade, the market has become increasingly crowded with biologics targeting IL-17, IL-23, and IL-12/23 pathways, as well as oral small molecules such as JAK inhibitors. Although safety concerns related to broader JAK inhibition, including FDA black box warnings for cardiovascular events and malignancies, have prompted increased caution, JAK inhibitors as a class remain an actively explored option across many immune-mediated conditions.

Enter TYK2 inhibition, a mechanistically distinct option that modulates a narrower set of immune signals — including IL-12, IL-23, and type I interferons — without broadly suppressing the JAK-STAT pathway. This unique profile offers the promise of preserving efficacy while reducing safety risks, particularly those related to systemic immunosuppression.

EULAR 2025 Spotlight: Sotyktu’s Positive Phase 3 Readouts

At EULAR 2025, Bristol Myers Squibb shared pivotal data from its POETYK PsA-1 and PsA-2 trials, offering robust evidence of Sotyktu’s efficacy and safety in moderate-to-severe PsA.

• In POETYK PsA-1 (n=670), 54.2% of patients treated with Sotyktu achieved ACR20 (American College of Rheumatology improvement of 20%) at Week 16 versus 34.1% for placebo (P < 0.0001).
• In POETYK PsA-2 (n=730), ACR20 rates were 54.2% for Sotyktu at Week 16 compared to 39.4% for placebo (P = 0.0002).

Importantly, both trials also achieved multiple secondary endpoints related to joint pain, skin symptoms, and physical function — all without deviating from the safety profile observed in previous psoriasis studies. These outcomes were consistent regardless of prior biologic or small molecule use, reinforcing the potential utility of Sotyktu across lines of therapy. Notably, Rinvoq (upadacitinib, AbbVie) and Xeljanz (tofacitinib, Pfizer), two JAK inhibitors approved for psoriatic arthritis, are currently restricted to second-line use in Europe, consistent with the approval status of most JAK inhibitors.

A Differentiated Oral Option

Sotyktu’s oral administration, coupled with its selective mechanism of action (MoA), represents a meaningful advancement. While biologics dominate first- and second-line treatment, real-world adherence remains a challenge due to discomfort and logistical concerns surrounding injectable treatments, insurance coverage, and cold-chain logistics. A once-daily oral alternative with robust clinical data could fill a significant unmet need, especially among patients unwilling or unable to initiate injectable therapies.

In contrast to JAK inhibitors, the absence of FDA black box warnings could also be a defining differentiator for Sotyktu in the minds of both prescribers and payers. That said, post-marketing surveillance will be critical to solidify this safety narrative and validate long-term use.

Broader TYK2 Ambitions: Beyond PsA

PsA may be just the beginning. Sotyktu is already FDA-approved for moderate-to-severe plaque psoriasis, and its development pipeline spans a range of autoimmune conditions, including:

• Systemic Lupus Erythematosus (SLE) — Phase 3 POETYK SLE trial (results expected Q1 2026)
• Sjögren’s Syndrome and Lichen Planopilaris, among others

However, efforts to expand into gastroenterology have faced setbacks: Sotyktu trials in Ulcerative Colitis and Crohn’s Disease were terminated after failing to meet primary endpoints. Still, the sheer breadth of ongoing studies suggests that selective TYK2 inhibition could become a cornerstone of immunology portfolios, particularly if supported by differentiated data in high-burden indications like SLE.

Strategic Implications for Pharma and Payers

The EULAR 2025 readouts reinforce the increasing importance of oral therapies that balance efficacy, safety, and convenience. If Bristol Myers Squibb can sustain this momentum, Sotyktu may emerge as a valuable competitor in both biologic-experienced and biologic-naïve populations, particularly in markets wary of systemic JAK inhibitor risks.

Moreover, Sotyktu exemplifies the broader “pipeline-in-a-product” trend in immunology — where assets are intentionally developed across multiple autoimmune indications to maximize life cycle value. As regulatory agencies show greater openness to mechanism-based expansion, TYK2 inhibitors could anchor multi-indication franchises in the years to come.

About The Authors:

Shikha Gianchandani, Gaja Gasiorek (MPhil), and Pooja Goyal (MSPharm) are with Lifescience Dynamics.