JAK Inhibitors in Inflammatory Bowel Disease: Mechanism, Indications, and Safety Considerations
Muhammad Waqas, Ex Resident Pharmacist at Shifa International Hospitals Limited, shared on LinkedIn:
“𝗝𝗔𝗞 𝗜𝗻𝗵𝗶𝗯𝗶𝘁𝗼𝗿𝘀 𝗶𝗻 𝗜𝗕𝗗
1. Mechanism of Action: Janus kinase (JAK) inhibitors block intracellular JAK-STAT signaling,reduces cytokine-driven inflammation. They are oral small molecules (unlike biologics) and act on multiple cytokine pathways.
𝟮. 𝗔𝗽𝗽𝗿𝗼𝘃𝗲𝗱 𝗝𝗔𝗞 𝗜𝗻𝗵𝗶𝗯𝗶𝘁𝗼𝗿𝘀
Tofacitinib: Oral, non-selective JAK1/3 inhibitor
Upadacitinib: Oral, selective JAK1 inhibitor
Filgotinib Oral, selective JAK1 inhibitor
Peficitinib Investigational / clinical trials JAK1/3 inhibitor
3. Indications / Patient Selection
• Moderate-to-severe UC failing:
• Corticosteroids
• Immunomodulators (azathioprine, 6-MP)
• Biologics (biologic-refractory disease.)
• Useful for patients preferring oral therapy
𝟰. 𝗗𝗼𝘀𝗶𝗻𝗴 (𝗲𝘅𝗮𝗺𝗽𝗹𝗲)
• 𝗧𝗼𝗳𝗮𝗰𝗶𝘁𝗶𝗻𝗶𝗯:
• 𝗜𝗻𝗱𝘂𝗰𝘁𝗶𝗼𝗻: 𝟭𝟬 𝗺𝗴 𝗼𝗿𝗮𝗹𝗹𝘆 𝗕𝗜𝗗 𝗳𝗼𝗿 𝟴 𝘄𝗲𝗲𝗸𝘀
• 𝗠𝗮𝗶𝗻𝘁𝗲𝗻𝗮𝗻𝗰𝗲: 𝟱–𝟭𝟬 𝗺𝗴 𝗕𝗜𝗗 (𝗯𝗮𝘀𝗲𝗱 𝗼𝗻 𝗿𝗲𝘀𝗽𝗼𝗻𝘀𝗲)
• 𝗨𝗽𝗮𝗱𝗮𝗰𝗶𝘁𝗶𝗻𝗶𝗯:
• 𝗜𝗻𝗱𝘂𝗰𝘁𝗶𝗼𝗻: 𝟰𝟱 𝗺𝗴 𝗱𝗮𝗶𝗹𝘆
• 𝗠𝗮𝗶𝗻𝘁𝗲𝗻𝗮𝗻𝗰𝗲: 𝟭𝟱–𝟯𝟬 𝗺𝗴 𝗱𝗮𝗶𝗹𝘆
𝟱. 𝗔𝗱𝘃𝗲𝗿𝘀𝗲 𝗘𝗳𝗳𝗲𝗰𝘁𝘀 / 𝗦𝗮𝗳𝗲𝘁𝘆
• Infections: Herpes zoster, serious bacterial/fungal infections
• Thrombosis risk: Deep vein thrombosis, pulmonary embolism (especially at higher doses or risk factors)
• Lipid abnormalities: ↑ LDL, ↑ HDL
• Hematologic: Anemia, leukopenia, lymphopenia
• Other: GI perforation (rare), elevated liver enzymes
𝟲. 𝗠𝗼𝗻𝗶𝘁𝗼𝗿𝗶𝗻𝗴
• Baseline: CBC, LFTs, lipid profile, TB and hepatitis screening
• Ongoing: CBC, LFTs, lipid profile periodically; monitor for infections”
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