New targeted therapy could bring relief to people with lichen planus

Mayo Clinic researchers have identified a targeted therapy that could bring relief to people living with lichen planus, a chronic inflammatory skin condition of the skin, hair, nails, mouth and genitals. They described their findings in a study published in the Journal of Clinical Investigation that described their first-in-human, phase 2 clinical trial.

The researchers identified unique molecular and cellular changes in the skin with lichen planus, particularly an overactive immune response involving specific types of T cells, a crucial immune system component.

The researchers then used baricitinib, a medication that selectively blocks the specific inflammatory pathways of lichen planus, to treat patients in the study.

Cytokines are small proteins that are crucial in controlling the growth and activity of other immune system cells and blood cells. They include interferon-gamma, a critical signal in normal antiviral responses and aberrant in lichen planus, which leads to immune cells attacking normal cells.

Janus kinase (JAK) enzymes play a crucial role in the body's inflammatory response. Baricitinib is an oral JAK 1/2 inhibitor that interrupts the signaling pathway of interferon-gamma by blocking these enzymes. This helps reduce inflammation and suppress the overactive immune response that contributes to these conditions.

The patients with treatment-refractory disease experienced early and sustained clinical response to the treatment, resulting in an 83% improvement in symptom responsiveness within 16 weeks of treatment, a marked improvement over baseline. The therapy also rapidly reduced interferon activity, a key signaling molecule in the disease, as well as reduced the specific, pathogenic T-cells.

This research is an important step in connecting the dots in understanding - and treating -autoimmune and inflammatory diseases. These findings provide a potential new, effective, disease-specific treatment option for lichen planus and therapeutic targets for other inflammatory diseases."

Aaron R. Mangold, M.D., senior author, dermatologist and researcher with the Mayo Clinic Comprehensive Cancer Center at Mayo Clinic, Phoenix

Lichen planus affects 1 to 2% of the general population, altering the quality of life for patients due to intense itching or pain. On the skin, lichen planus often appears as purple, itchy, flat bumps that develop over several weeks. In the mouth and genital mucosa, lichen planus forms lacy white patches, sometimes with painful sores.

Treatment of lichen planus is challenging, and therapeutic options have remained stagnant. To date, researchers have not developed any disease-specific medications for lichen planus. While there is no cure, various treatments can help manage symptoms. However, these treatments can come with common side effects including skin thinning, weakened immune system and increased risk of infection. There is also a need for options for those who don't respond to treatment. Specific subtypes, such as hypertrophic and mucosal lichen planus, are chronic and may not respond to treatment.

This research provides valuable insights into the pathophysiology of lichen planus and demonstrates the potential of baricitinib as a promising treatment option, says Dr. Mangold, a Mayo Clinic consultant in the Department of Dermatology who studies rare inflammatory conditions and new therapeutics, and conducted an earlier phase 2 Mayo Clinic-led clinical trial to target these cells.