W. Alberto Sifuentes Giraldo: Targeting the JAK-STAT Pathway in Behçet’s Disease
W. Alberto Sifuentes Giraldo, Rheumatologist at Hospital Nuestra Señora de Sonsoles (Sacyl), shared a post on LinkedIn about a recent article by Fadi Hassan et al, published in Seminars in Arthritis and Rheumatism, adding:
“Behçet’s Disease (BD) pathogenesis involves dysregulated innate and adaptive immunity with elevated proinflammatory cytokines (e.g., IL-6, IL-12, IL-23, interferon-γ), many signaling via the Janus kinase
(JAK)–signal transducer and activator of transcription (STAT) pathway (JAK-STAT pathway).
JAK inhibitors therefore offer a mechanistic advantage by targeting multiple pathways. Additional practical benefits include oral administration, relatively rapid onset, and short half-life, which allow flexible treatment management.
Several JAK inhibitors have been increasingly investigated in BD across a range of clinical manifestations. However, current evidence remains limited and heterogeneous. Due to this, Hassan et al. conducted a systematic review to evaluate their efficacy and safety in BD.
Key Results Seventeen studies (99 patients)—mainly case reports and small observational cohorts of high methodological quality—evaluated only tofacitinib, baricitinib, or upadacitinib. Patients were highly treatment-refractory (prior failure of conventional and biologic therapies).
- Upadacitinib was the most studied agent, showing an overall response rate of 85.2 percent and complete remission in 59.3 percent in a multicenter study.
- Efficacy was seen across domains, with the most consistent responses in intestinal BD (clinical and endoscopic remission) and frequent glucocorticoid-sparing effects.
Safety Findings aligned with known JAK-inhibitor profiles: mainly mild-to-moderate infections and manageable laboratory abnormalities. No clear signal for increased thrombotic events was observed, though follow-up was limited.
Conclusions JAK inhibitors show promising efficacy in refractory and multisystem BD, especially gastrointestinal involvement (data for other domains remain limited). The safety profile appears consistent with existing knowledge, but longer follow-up and high-quality randomized controlled trials are needed to confirm their role.”
Title: Efficacy and Safety of Janus Kinase Inhibitors in Behçet’s Disease: A Systematic Literature Review
Authors: Fadi Hassan a b, Mahmud Omar c d, Helana Jeries a b, Fatma Alibaz e, Mohammad E. Naffaa
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