New study highlights the potential of jaktinib in treating active axial spondyloarthritis

A recent phase II clinical trial published in Rheumatic and Musculoskeletal Diseases has revealed promising outcomes for jaktinib hydrochloride, a Janus kinase inhibitor (JAK) , in managing active radiographic axial spondyloarthritis (r-axSpA). This multicenter, randomized, double-blind, placebo-controlled study evaluated the drug’s efficacy and safety over a 16-week period, providing new insights into potential oral therapeutic options for rheumatologists treating this chronic inflammatory condition. 

The study involved 107 adults with active r-axSpA, meeting the modified New York criteria and unresponsive to NSAIDs. By week 16, jaktinib demonstrated marked improvements, with ASAS 20 response rates of 61.1% (100 mg), 57.1% (75 mg), and 33.3% (placebo). ASAS 40 response rates followed a similar pattern, with 47.2%, 37.1%, and 13.9% for the respective groups, highlighting a dose-dependent trend favoring the 100 mg twice-daily regimen. Safety data further supported the potential of jaktinib, showing comparable incidences of treatment-emergent adverse events across groups, with no reports of major adverse cardiovascular events, malignancies, thromboembolic events, or deaths, underscoring its tolerability. 

Jaktinib is a small-molecule inhibitor of JAK with potent activity against JAK2 and tyrosine kinase 2 (TYK2), while showing reduced effects on JAK3 and minimal effects on JAK1. In axSpA, pathogenic factors such as mechanical stress, infections, and gut microbiota imbalance activate interleukin-23 (IL-23). Through JAK2/TYK2 signaling, IL-23 promotes the proliferation and differentiation of type 17 helper T cells, leading to increased secretion of proinflammatory cytokines, including tumor necrosis factor (TNF), interferon-γ, interleukin-22 (IL-22), and IL-17. The therapeutic efficacy of jaktinib in axSpA could be attributed to its ability to inhibit the JAK/STAT signaling pathway, suppressing the inflammatory cascade triggered by IL-23 and IL-17 and reducing the production of proinflammatory cytokines. 

Jaktinib has demonstrated efficacy and safety in clinical trials for myelofibrosis, effectively reducing spleen size, improving anemia, and alleviating a range of clinical symptoms, all with a favorable tolerability profile. Jaktinib hydrochloride, identified by the compound code ZG0128, is a novel JAK inhibitor, with its active pharmaceutical ingredient being Jaktinib (ZG0163). As a broad-spectrum inhibitor, jaktinib targets non-receptor JAKs (JAK1, JAK2, JAK3), type II receptor tyrosine kinases, FMS-like tyrosine kinase 3, and c-Kit. These pathways are crucial for mediating cytokine and growth factor signaling involved in hematopoietic, inflammatory, and immune functions. Its ongoing exploration in myelofibrosis treatment highlights its potential to address key clinical needs. 

This study builds on existing knowledge of JAK inhibitors as effective therapies for axSpA, adding jaktinib to the list of potential treatment options. Its efficacy in alleviating disease symptoms and its favorable safety profile position jaktinib as a promising alternative for patients with an inadequate response to NSAIDs. With further research, jaktinib could play a significant role in broadening the therapeutic landscape for axSpA, offering rheumatologists an additional oral treatment option for managing this challenging condition. 

References  

  1. Wang J, Bao C, Dai Q, Xu A, Ye Y. Efficacy and safety of jaktinib hydrochloride tablets in active axial spondyloarthritis: a multicentre, randomised, double-blind, placebo-controlled phase II clinical trial. RMD Open. 2025 Jan 2;11(1):e004865. 
  2. Zhao M, Zhang H, Ma S, Gong S, Wei C, Miao L, Zhao W. Clinical pharmacokinetic characteristics of Jaktinib in subjects with hepatic impairment in a phase I trial. Drug Metab Pharmacokinet. 2024 Dec;59:101030.