Lessons from extended induction and practical evidence for improving tofacitinib therapy in ulcerative colitis

Table 1 Studies of extended induction tofacitinib therapy in ulcerative colitis

Ref.	Design	Patients	Clinical response	Adverse events	Severity
Sandborn et al[8]	Phase 2/3 randomized controlled	Moderate to severe colitis	52% delayed responders. 44% remission at 36th month		Similar 8 weeks vs 16 weeks
Sandborn et al[7]	Three phase 3 randomized controlled trials (OCTAVE induction 1/2, sustain)	Moderate to severe ulcerative colitis, prior conventional or biologic therapy	18.5% (induction 1), 16.6% (induction 2), 18.5% (induction 1), 16.6% (induction 2)	Infections, herpes zoster, non-melanoma skin cancer, cardiovascular events, lipid changes	Serious infections higher in induction; similar in maintenance
Sandborn et al[10]	Phase 2 randomized controlled trial, dose-ranging	Moderate to severe ulcerative colitis. 194 patients	61% (10 mg twice daily), 78% (15 mg twice daily). Remission: 48% (10 mg twice daily), 41% (15 mg twice daily	Lipid changes, neutropenia
Paschos et al[11]	Systemic review and meta-analysis	Moderate to severe ulcerative colitis, 29%-46.7% prior anti-tumor necrosis factor therapy, mean age 40-43 (1220 patients)	Odds ratio = 2.95 (response). Remission: Odds ratio = 3.84 (response)	Infections (nasopharyngitis), adverse events	Serious infections are rare similar to placebo
Lin et al[12]	Systemic review and meta-analysis	Moderate to severe ulcerative colitis, partial Mayo score 5-9, extensive disease, 26-46 years, 39%-69% male (2612 patients)	58% (8 weeks), 61% (12-16 weeks), 51% (24-26 weeks), 51% (52 weeks). Remission: 39% (8 weeks), 43% (12-16 weeks), 40% (24-26 weeks), 43% (52 weeks)	Serious infections 1.6-1.7 per 100 patient-years, herpes zoster 3.2-3.3 per 100 patient-years, cardiovascular events 0.16-0.29 per 100 patient-years
Taxonera et al[13]	Systematic review and meta-analysis of real-world studies	Moderate to severe, highly refractory ulcerative colitis, 11.6% biologic-naive (1162 patients)	62.1% (8 weeks), 64.2% (12-16 weeks), 50.8% (24 weeks), 41.8% (52 weeks). Remission: 34.7% (8 weeks), 47% (12-16 weeks), 38.3% (24 weeks)	8.9 per 100 patient-years (serious adverse events), 6.9 per 100 patient-years (herpes zoster)	Similar
Taneja et al[14]	Systematic review and meta-analysis (randomized controlled trials and real-world studies)	Moderate to severe ulcerative colitis, biologic-naive and experienced	59.4% (8 weeks), 49% (6 months), 51% (1 year). Remission: 29.8% (8 weeks), 32.3% (6 months), 38% (1 year)	4.4 per 100 patient-years (infections), 0.9 per 100 patient-years (cardiovascular/malignancy)	Higher at higher dose
Lichtenstein et al[15]	Phase 3, multicenter, open-label extension	Moderate to severe ulcerative colitis, prior randomized controlled trial participants (914 patients)		Serious adverse events 10.4%, severe 78%, serious infections 2.6% (5 mg), 1.8% (10 mg), malignancy 1.2% (10 mg)
Chaparro et al[16]	Prospective, multicenter, real-world registry (ENEIDA)	Refractory ulcerative colitis, prior biologic failure, partial Mayo score (113 patients)	60% (8 weeks). Remission: 31% (8 weeks)	Adverse events (hypercholesterolemia, herpes zoster, infections), discontinuations	15% adverse events, 6% discontinued for adverse events