What is the efficacy and safety of deucravacitinib (TYK2 inhibitor) for treating cutaneous sarcoidosis?

Deucravacitinib for Cutaneous Sarcoidosis: Current Evidence

There are currently no published case reports or literature specifically on the use of deucravacitinib for cutaneous sarcoidosis. Based on the available evidence, deucravacitinib has not been studied or reported for the treatment of cutaneous sarcoidosis in any published literature.

Current Treatment Options for Cutaneous Sarcoidosis

The European Respiratory Society (ERS) clinical practice guidelines outline a stepwise approach to treating cutaneous sarcoidosis:

• First-line: Topical glucocorticoids for cosmetically important skin lesions 1
• Second-line: Systemic glucocorticoids (prednisone/prednisolone) for significant disease or relapse 1
• Third-line: Hydroxychloroquine or chloroquine for steroid-sparing or continued disease 1
• Fourth-line: Methotrexate for continued disease or relapse 1
• Fifth-line: Infliximab for refractory cases 1
• Additional options: Adalimumab for continued disease after infliximab 1

JAK Inhibitors in Sarcoidosis

• Tofacitinib (JAK inhibitor) has shown promising results in cutaneous sarcoidosis in a small open-label trial, with 6 out of 10 patients showing complete response 2
• The ERS guidelines mention tofacitinib as a potential additional agent for cutaneous sarcoidosis, but note it should be used on a case-by-case basis 1
• The mechanism appears to be through inhibition of type 1 immunity, particularly CD4+ T cell-derived IFN-γ and other type 1 cytokines 2

Deucravacitinib: Mechanism and Evidence in Other Conditions

• Deucravacitinib is a first-in-class selective tyrosine kinase 2 (TYK2) inhibitor that binds to the regulatory domain of TYK2 3
• It interferes with signaling of IL-23, IL-12, and type I interferons, which are cytokines involved in inflammatory pathways 3, 4
• Deucravacitinib has been approved for moderate-to-severe plaque psoriasis with nearly 60% of patients achieving PASI 75 at 16 weeks 3, 5
• It has demonstrated superior efficacy to apremilast in psoriasis trials 5, 4
• The safety profile appears favorable with no reports of serious infections, thromboembolic events, or significant laboratory abnormalities that are concerns with other JAK inhibitors 4, 6

Gaps in Evidence and Clinical Implications

• There is no published evidence on deucravacitinib specifically for cutaneous sarcoidosis 1
• The ERS guidelines note that several agents (including apremilast) have been studied in open-label trials for cutaneous sarcoidosis, but lack confirmation in larger studies or case series 1
• Given the mechanism of action targeting pathways relevant to sarcoidosis and the positive results of tofacitinib (another JAK pathway inhibitor) in sarcoidosis, deucravacitinib might theoretically have potential 2, 4

Clinical Considerations

• For patients with cutaneous sarcoidosis, following the established treatment algorithm is recommended, starting with topical glucocorticoids and progressing through systemic options as needed 1
• Infliximab has the strongest evidence for refractory cutaneous sarcoidosis based on randomized controlled trials 1
• Any consideration of deucravacitinib would be experimental and off-label, requiring careful discussion of risks and benefits 1, 3
• Monitoring for potential adverse effects would be prudent if considering deucravacitinib, though specific monitoring guidelines for its use in sarcoidosis cannot be provided due to lack of evidence 6