Emerging role of Janus kinase inhibitors in ulcerative colitis management

Table 1 Comparison of Janus kinase inhibitors in ulcerative colitis

Parameters	First-generation JAK inhibitors	Next-generation JAK inhibitors
	Tofacitinib	Upadacitinib	Filgotinib
JAK selectivity	It mainly inhibits JAK1 and JAK3 with less effect on JAK2[12]	It specifically targets JAK1[24]	Targets JAK1[27]
Clinical trials	OCTAVE trials[13]	U-ACHIEVE and U-ACCOMPLISH trials[24]	SELECTION trials, MANTA trials[28,31]
Dose available	10 mg drug dose for induction and 5 mg/10 mg for maintenance[14]	45 mg drug dose for induction. And 15 mg/30 mg for maintenance[25]	200 mg drug dose for induction and 200 mg/100 mg for maintenance[28]
Dosing frequency	Twice daily[14]	Once daily[25]	Once daily[28]
Pharmacokinetics	It is primarily metabolized by hepatic cytochrome P450 enzymes (CYP3A4 and CYP2C19), with approximately 70% cleared hepatically and 30% renally[45]	Upadacitinib is mainly metabolized by CYP3A4[47]	Filgotinib is metabolized by carboxyl esterase isoform 2[47]
	It has a half-life of approximately 3 to 6 hours[45]	The half-life of upadacitinib ranges from 8 to 14 hours[46]	For Filgotinib, the half-life is approximately 7 hours for the parent drug and 19 hours for its metabolite[47]
Efficacy	It was proven to be effective in inducing and maintaining remission compared to placebo in randomized controlled trials. Induction remission rates in OCTAVE 1 and 2 were 18.5% and 16.6% vs 8.2% and 3.6% for placebo; maintenance remission at week 52 was 34.3% (5 mg) and 40.6% (10 mg)[11]. Real-world response at week 8 was 74%, with 44% achieving steroid-free remission at week 26[12]	Upadacitinib is considered significantly effective in inducing and maintaining remission, with the 45 mg dose demonstrating relatively higher efficacy compared to tofacitinib and filgotinib[25,26]. At week 96, clinical remission was achieved in 76% (15 mg) and 74% (30 mg) of patients. Endoscopic remission was maintained in 73% of patients receiving 30 mg who had achieved it at baseline[48]	Proven to be significantly effective in inducing and maintaining remission[27,28]. By week 58, 37.2% (200 mg) and 23.8% (100 mg) achieved remission vs 11.2% and 13.5% with placebo[49]
Safety	Its use is associated with various infections (viral, bacterial, fungal, and opportunistic), elevated cholesterol, and malignancies[19]. Major cardiovascular events and venous thromboembolism rates are higher compared to other TNF inhibitors[20]	Adverse effects include lymphopenia, elevated creatine phosphokinase, hepatic disorders, serious infections, neutropenia, herpes zoster, and acne. The incidence of major cardiovascular events and thromboembolism is comparable to other treatments, with higher rates observed primarily in patients with a history of VTE or cardiovascular disease[25,26]	Adverse effects include mild infections and anemia. No major cardiovascular or thromboembolic events have been reported with its use based on the limited available data[30]

JAK: Janus kinase; VTE: Venous thromboembolic event.