Updated review of Janus kinase inhibitors for the management of inflammatory bowel disease

Table 1 Indications and pharmacological properties of approved Janus kinase inhibitors for the management of inflammatory bowel disease

Parameter	Tofacitinib	Upadacitinib	Filgotinib
JAK selectivity	JAK1 > JAK3 > JAK2	JAK1 > JAK2 > JAK3 > TYK2	JAK1 > JAK2 > JAK3
Approved indication	Moderate to severe UC	Moderate to severe UC and CD	Moderate to severe UC (EMA-approved only)
Induction dosing	10 mg BID for 8 weeks	45 mg OD for 8-12 weeks	200 mg OD
Maintenance dosing	5 mg BID (or 10 mg if needed short-term)	15 mg or 30 mg OD based on response	200 mg OD
Efficacy (induction)	Clinical remission: 18%-20% (OCTAVE 1 & 2)	Clinical remission: 26%-34% (UC trials), 44% (CD-CELEST)	Clinical remission: 26.1% vs 15.3% placebo (SELECTION)
Efficacy (maintenance)	34%-41% remission at 52 weeks (OCTAVE sustain)	42%-52% remission in UC; 40%-47% in CD (CELEST-OLE)	37.2% remission at 58 weeks
Real-world data	Established role in UC, encouraging data in ASUC, however no benefit in CD	Effective in UC and CD, including tofacitinib-refractory patients	Emerging for UC, limited data in CD
Pregnancy category	Category C (not recommended)	Category D (not recommended)	Contraindicated (reproductive toxicity in animal studies)
Regulatory approval	FDA & EMA approved for UC	FDA & EMA approved for UC and CD	EMA approved; FDA rejected application

JAK: Janus kinase; TYK2: Tyrosine kinase 2; UC: Ulcerative colitis; CD: Crohn’s disease; EMA: European Medicines Agency; BID: Twice daily; OD: Once daily; FDA: Food and Drug Administration.