FOCUS ON
- Wednesday, 30 September
- 14:15 - 15:45 CEST
- Hall C
Presentation details:
Understanding the mechanism of action
Melinda Gooderham, Canada
Janus kinase (JAK) inhibitors have rapidly reshaped the therapeutic landscape across dermatology, from atopic dermatitis and alopecia areata to psoriatic disease, vitiligo, and hidradenitis suppurativa. Yet their clinical behaviour including efficacy, speed of onset, and safety signals, can only be understood with proper knowledge of their mechanism.
This presentation provides an in-depth, mechanism-focused account of how JAK inhibitors work and why those mechanistic differences matter.
We begin with the JAK-STAT signalling pathway: how cytokine receptor engagement activates the four JAK family members (JAK1, JAK2, JAK3, TYK2), how downstream STAT phosphorylation drives gene transcription, and how this single pathway transmits the signals of dozens of cytokines central to inflammatory skin disease.
From this foundation, we examine how selectivity is engineered, distinguishing first-generation pan-JAK inhibitors from newer JAK1-preferential and allosteric TYK2 agents, and how receptor-level pharmacology translates into distinct cytokine-blockade profiles.
The talk then connects mechanism to the clinic: why specific JAK dependencies make certain diseases more or less responsive, how selectivity shapes the benefit–risk profile, and how an understanding of on-target versus off-target effects informs monitoring and patient selection. Throughout, the emphasis is on giving clinicians a durable mechanistic framework they can apply as new molecules and indications continue to emerge.
Key learning objectives
- Describe the JAK-STAT signalling pathway and the role of JAK1, JAK2, JAK3, and TYK2 in transmitting the cytokine signals that drive inflammatory skin disease.
- Differentiate the mechanisms and selectivity profiles of currently available JAK and TYK2 inhibitors, and explain how these differences influence efficacy and safety.
- Apply a mechanistic understanding of JAK inhibition to drug selection, monitoring, and patient counselling across dermatologic indications.
Presentation details:
Emerging JAK inhibitors and combination treatments
Bruno Duarte, Portugal
JAK inhibitors have transformed the management of several immune-mediated skin diseases. In just six years, multiple topical and systemic JAK inhibitors have been approved across a range of dermatologic indications. However, the story of JAK inhibition is far from complete.
From new molecules with modified selectivity profiles to label expansions for existing agents, the therapeutic landscape continues to evolve and a number of exciting approvals are anticipated in the coming years. But while these drugs present remarkable efficacy in monotherapy, many patients continue to experience suboptimal responses; thus, Dermatologists are increasingly exploring the usefulness of off label combination strategies in real-world practice.
Overcoming treatment plateaus in resistant atopic dermatitis or hasten onset of responses in slower-responding disorders such as alopecia areata or vitiligo might be potentially feasible, and safe, with emerging combinations between JAK inhibitors and other agents already available in clinical practice.
Key Learning Objectives
- Review the evolving JAK inhibitor pipeline, including emerging molecules and anticipated indication expansions relevant to dermatologic practice.
- Examine the rationale and available evidence supporting off label combination strategies involving JAK inhibitors and both immunomodulatory andnnon-immunomodulatory agents.
- Discuss practical considerations for the use of combination approaches, including patient selection, potential benefits and safety considerations.