JAK Inhibitors in Inflammatory Bowel Disease: Mechanism, Indications, and Safety Considerations
Muhammad Waqas, Ex Resident Pharmacist at Shifa International Hospitals Limited, shared on LinkedIn:
“๐๐๐ ๐๐ป๐ต๐ถ๐ฏ๐ถ๐๐ผ๐ฟ๐ ๐ถ๐ป ๐๐๐
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.
๐ฎ. ๐๐ฝ๐ฝ๐ฟ๐ผ๐๐ฒ๐ฑ ๐๐๐ ๐๐ป๐ต๐ถ๐ฏ๐ถ๐๐ผ๐ฟ๐
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
โข Moderate-to-severe UC failing:
โข Corticosteroids
โข Immunomodulators (azathioprine, 6-MP)
โข Biologics (biologic-refractory disease.)
โข Useful for patients preferring oral therapy
๐ฐ. ๐๐ผ๐๐ถ๐ป๐ด (๐ฒ๐
๐ฎ๐บ๐ฝ๐น๐ฒ)
โข ๐ง๐ผ๐ณ๐ฎ๐ฐ๐ถ๐๐ถ๐ป๐ถ๐ฏ:
โข ๐๐ป๐ฑ๐๐ฐ๐๐ถ๐ผ๐ป: ๐ญ๐ฌ ๐บ๐ด ๐ผ๐ฟ๐ฎ๐น๐น๐ ๐๐๐ ๐ณ๐ผ๐ฟ ๐ด ๐๐ฒ๐ฒ๐ธ๐
โข ๐ ๐ฎ๐ถ๐ป๐๐ฒ๐ป๐ฎ๐ป๐ฐ๐ฒ: ๐ฑโ๐ญ๐ฌ ๐บ๐ด ๐๐๐ (๐ฏ๐ฎ๐๐ฒ๐ฑ ๐ผ๐ป ๐ฟ๐ฒ๐๐ฝ๐ผ๐ป๐๐ฒ)
โข ๐จ๐ฝ๐ฎ๐ฑ๐ฎ๐ฐ๐ถ๐๐ถ๐ป๐ถ๐ฏ:
โข ๐๐ป๐ฑ๐๐ฐ๐๐ถ๐ผ๐ป: ๐ฐ๐ฑ ๐บ๐ด ๐ฑ๐ฎ๐ถ๐น๐
โข ๐ ๐ฎ๐ถ๐ป๐๐ฒ๐ป๐ฎ๐ป๐ฐ๐ฒ: ๐ญ๐ฑโ๐ฏ๐ฌ ๐บ๐ด ๐ฑ๐ฎ๐ถ๐น๐
๐ฑ. ๐๐ฑ๐๐ฒ๐ฟ๐๐ฒ ๐๐ณ๐ณ๐ฒ๐ฐ๐๐ / ๐ฆ๐ฎ๐ณ๐ฒ๐๐
โข Infections: Herpes zoster, serious bacterial/fungal infections
โข Thrombosis risk: Deep vein thrombosis, pulmonary embolism (especially at higher doses or risk factors)
โข Lipid abnormalities: โ LDL, โ HDL
โข Hematologic: Anemia, leukopenia, lymphopenia
โข Other: GI perforation (rare), elevated liver enzymes
๐ฒ. ๐ ๐ผ๐ป๐ถ๐๐ผ๐ฟ๐ถ๐ป๐ด
โข Baseline: CBC, LFTs, lipid profile, TB and hepatitis screening
โข Ongoing: CBC, LFTs, lipid profile periodically; monitor for infections”

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