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TYK2 inhibition with deucravacitinib ameliorates erosive oral lichen planus
Kim Natalie Stolte1,2, Alberto Mesas-Fernández2, Katharina Meier3
1Department of Periodontology, Oral Medicine and Oral Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Abstract:
Erosive oral lichen planus (OLP) is a challenging disease. This T cell driven disorder frequently shows a treatment unresponsive course and strongly limits patients' quality of life. The disease lacks FDA or EMA approved drugs for its treatment and the efficacy of the commonly administered treatments (i.e. topical and systemic steroids, steroid sparing agents) is often only partial. Although the etiopathogenesis of the disease still needs to be fully elucidated, recent advances helped to identify interferon-ɣ (IFN-ɣ) as a pivotal cytokine in OLP pathogenesis, thus making the interference with its signalling a therapeutic target. Janus kinase (JAK) inhibitors therefore gained relevance for their inhibitory effect on IFN-ɣ signalling. While some drugs such as abrocitinib, upadacitinib, tofacitinib directly interfere with IFN-ɣ signalling through blockade of JAK1 and/or JAK2, deucravacitinib, a selective TYK-2 inhibitor indirectly interferes on IFN-ɣ activation through interference with interleukin (IL)-12, a potent promotor for Th1/IFN-ɣ responses. This mechanism of action makes deucravacitinib a candidate drug for the treatment of OLP. Here we provide initial evidence that deucravacitinib 6 mg daily has a beneficial effect in three patients with oral OLP.
Insights
Deucravacitinib shows promise for treating oral lichen planus (OLP), a difficult T cell disorder. Initial findings suggest this selective TYK-2 inhibitor may offer a beneficial therapeutic option for OLP patients.
Area of Science:
- Immunology
- Dermatology
- Pharmacology
Background:
- Erosive oral lichen planus (OLP) is a chronic T cell-driven condition with limited treatment options and significant impact on quality of life.
- Current therapies, including corticosteroids, offer only partial efficacy and lack specific FDA/EMA approval for OLP.
- Interferon-gamma (IFN-ɣ) is identified as a key cytokine in OLP pathogenesis, highlighting its signaling pathways as a therapeutic target.
Purpose of the Study:
- To evaluate the potential efficacy of deucravacitinib, a selective TYK-2 inhibitor, in treating patients with erosive oral lichen planus.
- To explore the therapeutic role of targeting the IL-12/IFN-ɣ axis in OLP management.
Main Methods:
- A case series involving three patients diagnosed with oral lichen planus.
- Administration of deucravacitinib at a dosage of 6 mg daily.
- Clinical observation of treatment response and patient outcomes.
Main Results:
- Deucravacitinib demonstrated a beneficial effect in all three treated patients with oral OLP.
- The selective TYK-2 inhibition by deucravacitinib appears to modulate the pathogenic pathways implicated in OLP.
Conclusions:
- Deucravacitinib represents a potential novel therapeutic candidate for erosive oral lichen planus.
- Targeting the IL-12/IFN-ɣ pathway with selective TYK-2 inhibitors warrants further investigation for OLP treatment.
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