Citations 2
Rapid response of lichen planus to baricitinib associated with suppression of cytotoxic CXCL13+CD8+ T cells
Kechter, Jacob , Do, Tran , Hughes, Alysia N., Zhang, Nan , Bogle, Rachael , Brumfiel, Caitlin M. , Boudreaux, Blake , Bhullar, Puneet , Nassir, Shams , Yousif, Miranda , Stockard, Alyssa , Leibovit-Reiben, Zachary , Ogbaudu, Ewoma , DiCaudo, David J. , Fox, Jennifer, Xing, Xianying , Zunich, Samantha , Branch, Emily, Billi, Allison C. , Pittelkow, Mark R. , Mangold, Aaron R. , Stockard, Alyssa , Hwang, Angelina S , Kechter, Jacob A, Patel, Meera H. , Yousif, Miranda L, Stockard, Alyssa L, Fox, Jennifer , Mangold, A R , Billi, Allison C , Hwang, Angelina , Li, Xing , Wasikowski, Rachael, Patel, Meera , Leibovit‐Reiben, Zachary , Gharaee‐Kermani, Mehrnaz , Kahlenberg, J. Michelle , Plazyo, Olesya , Tsoi, Lam C. , Gudjonsson, Johann E
Journal of Clinical Investigation | November 14, 2024 | Volume: 135 | Issue: 2 | Pages: No page available
BACKGROUND Cutaneous lichen planus (LP) is a recalcitrant, difficult-to-treat, inflammatory skin disease characterized by pruritic, flat-topped, violaceous papules on the skin. Baricitinib is an oral Janus kinase (JAK) 1/2 inhibitor that interrupts the signaling pathway of IFN-γ, a cytokine implicated in the pathogenesis of LP. METHODS In this phase II trial, 12 patients with cutaneous LP received 2 mg daily baricitinib for 16 weeks, accompanied by in-depth spatial, single-cell, and bulk transcriptomic profiling of pre- and posttreatment samples. RESULTS An early and sustained clinical response was seen, with 83.3% of patients responsive at week 16. Our molecular data identified a unique, oligoclonal IFN-γ, CD8 + , and CXCL13 + cytotoxic T cell population in LP skin and demonstrated a rapid decrease in IFN signature within 2 weeks of treatment, most prominently in the basal layer of the epidermis. CONCLUSION This study demonstrates the efficacy and molecular mechanisms of JAK inhibition in LP. TRIAL REGISTRATION NCT05188521 FUNDING Eli Lilly, Appignani Benefactor Funds, 5P30AR075043, Mayo Clinic Clinical Trials Stimulus Funds.
Targeting IL-1 controls refractory pityriasis rubra pilaris
Schmauch, Eloi , Severin, Yannik , Xing, Xianying , Mangold, Aaron R. , Conrad, Curdin , Johannsen, Pål, Kahlenberg, J. Michelle , Mellett, Mark , Navarini, Alexander A. , Nobbe, Stefan , Nilsson, Jakob , Linna-Kuosmanen, Suvi , Snijder, Berend , Contassot, Emmanuel , Kolios, Antonios G.A. , Mangold, A R , Johansen, Pål , Navarini, Alexander , Sarkar, Mrinal K , Satyam, Abhigyan , Tsoi, Lam C , French, Lars E , Nilsson, Jakob , Linna-Kuosmanen, Suvi , Kaikkonen, Minna U , Snijder, Berend , Kellis, Manolis , Gudjonsson, Johann E , Tsokos, George C. , Contassot, Emmanuel , Kolios, Antonios G A , Kahlenberg, J Michelle , Sarkar, Mrinal K. , Tsoi, Lam C.
Science Advances | July 3, 2024 | Volume: 10 | Issue: 27 | Pages: No page available
Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease with a poorly understood pathogenesis. Through a molecularly driven precision medicine approach and an extensive mechanistic pathway analysis in PRP skin samples, compared to psoriasis, atopic dermatitis, healed PRP, and healthy controls, we identified IL-1β as a key mediator, orchestrating an NF-κB–mediated IL-1β–CCL20 axis, including activation of CARD14 and NOD2. Treatment of three patients with the IL-1 antagonists anakinra and canakinumab resulted in rapid clinical improvement and reversal of the PRP-associated molecular signature with a 50% improvement in skin lesions after 2 to 3 weeks. This transcriptional signature was consistent with in vitro stimulation of keratinocytes with IL-1β. With the central role of IL-1β underscoring its potential as a therapeutic target, our findings propose a redefinition of PRP as an autoinflammatory keratinization disorder. Further clinical trials are needed to validate the efficacy of IL-1β antagonists in PRP.