利特昔替尼在青少年和成人斑秃治疗中的应用

Introduction: Rituxitinib, as a drug for the treatment of alopecia areata, has shown positive effects on both adolescents and adult patients, and its efficacy and safety have been verified in clinical trials. Oral ritixitinib is indicated for adults and adolescents 12 years and older with severe alopecia areata (circular hair loss). The effect is based on the irreversible inhibition of the Janus kinase JAK3 and the tyrosine protein kinase family TEC, and many affected individuals experience significant improvement in underlying inflammation-related autoimmune diseases.

Mechanism of action

It is a new type of irreversible inhibitor of Janus kinase 3 (JAK3) and the tyrosine kinase (TEC) kinase family expressed in hepatocellular carcinoma. By blocking signaling molecules and immune cell activity, it inhibits the immune system's attack on hair follicles, thereby promoting hair regeneration.

Specifically, ritixitinib covalently binds to Cys-909 of JAK3, a site where other JAK isoforms have serine residues, making ritixitinib a highly selective and irreversible JAK3 inhibitor. Other kinases have a cysteine ​​at a position equivalent to Cys-909 in JAK3, and some of these kinases belong to the TEC kinase family. It has been suggested that ritexitinib's dual activity on the JAK3 and TEC kinase families blocks cytokine signaling as well as the cytolytic activity of T cells, both of which are implicated in the pathogenesis of alopecia areata.

Efficacy of ritixitinib in the treatment of alopecia areata in adolescents and adults

In a randomized, double-blind, multinational Phase 2b/3 trial involving adults aged ≥18 years and adolescents aged 12-17 years with alopecia areata and ≥50% scalp hair loss, patients were randomized to receive ritixitinib 200 mg for 4 weeks, followed by 50 mg (n=132), ritixitinib 200mg for 4 weeks, followed by ritixitinib 30mg (n=130), ritixitinib 50mg (n=130), ritixitinib 30mg (n=130), and ritixitinib 10mg (n=63), placebo for 24 weeks.

At week 24, in the ritixitinib 200+50 mg and 200+30 mg groups, the proportions of patients who achieved the primary endpoint SALT score ≤ 20 (ie, scalp hair loss ≤ 20%) were 31%, 22%, 23%, 14%, and 2% respectively. The rates were 2% in the ritixitinib 50mg, 30mg and 10mg groups, respectively, and 2% in the combined placebo group. The long-term efficacy of ritixitinib in treating alopecia areata. By week 48 (i.e., the end of the 24-week extension period), the proportions of patients with SALT scores ≤ 20 in the ritixitinib 200+50mg and 200+30mg groups were 40%, 34%, 43%, and 31% respectively.

Contraindications

Ritexitinib should not be used in patients who are allergic to the active ingredient of ritexitinib, patients with active severe infections, especially tuberculosis, patients with severe liver dysfunction, and pregnant and lactating women.