Profile of Tofacitinib in the Treatment of Ulcerative Colitis: An Evidence-Based Review of Recent Data

Figures & data

Figure 1 Overview of the mechanism of action of Janus kinases (JAKs). Cytokine binding to type I/II receptor at the cytoplasmic side of the plasma membrane leads to JAK activation and phosphorylation. (Α) This subsequently initiates recruitment of two signal transducer and activator of transcription proteins (STATs) and induces their subsequent phosphorylation (Β). Once phosphorylated, STAT homodimerize or heterodimerize (C) and translocate to the nucleus where they regulate gene transcription (D).

Table 1 Summary of Market-Authorizing Trials for Tofacitinib in Ulcerative Colitis

Trial/Year	Phase	Arms	Size	Description	Selected Primary Endpoints		Selected Secondary Endpoints
					Clinical Remission (8 weeks) % (p)	Clinical Remission (52 weeks) % (p)	Mucosal Healing (8 weeks) % (p)	Mucosal Healing (52 weeks) % (p)	Sustained and Corticosteroid-Free Remission (24 and 52 weeks) % (p)
Sandborn et al, 2012 (38)	II	Placebo 0.5 mg BID 3 mg BID 10 mg BID 15 mg BID	48 31 33 33 49	Placebo vs Tofacitinib	10% 13% (p=0.76) 33% (p=0.01) 48% (p<0.001) 41% (p<0.001)	N/A	N/A	N/A	N/A
Sandborn et al, 2017 [OCTAVE Induction 1] (40)	III	Placebo 10 mg BID 15 mg BID	122 476 16	Placebo vs Tofacitinib	8.2% 18.5% (p=0.007) 43.8% (N/A)	N/A	15.6% 31.3% (p<0.001) 62.5% (N/A)	N/A	N/A
Sandborn et al, 2017 [OCTAVE Induction 2] (40)	III	Placebo 10 mg BID 15 mg BID	112 429 6	Placebo vs Tofacitinib	3.6% 16.6% (p<0.001) 50.0% (N/A)	N/A	11.6% 28.4% (p<0.001) 50.0% (N/A)	N/A	N/A
Sandborn et al, 2017 [OCTAVE Sustain] (40)	III	Placebo 5 mg BID 10 mg BID	198 198 197	Placebo vs Tofacitinib	N/A	11.1% 34.3% (p<0.001) 40.6% (p<0.001)	N/A	13.1% 37.4% (p<0.001) 45.7% (p<0.001)	5.1% 35.4% (p<0.001) 47.3% (p<0.001)

Abbreviations: BID, twice daily; N/A, not applicable.

Figure 2 Flowchart of participants progress through the OCTAVE trials.

Table 2 Real-World Studies

	Number	Previous Biologics	Dose	Outcomes
Weisshof et al (51)	58 patients (53 with UC)	93% failed TNFi 81% failed VDZ	60% (n=30) received 10 mg BID 38% (n=22) received 5 mg BID 2% (n=1) received 11mg ER OD	Week 8 clinical response 69%, clinical remission 33%, and corticosteroid-free remission 26% Week 52 corticosteroid-free remission 27%
Ungaro et al (52)	123 patients with UC	28.5% biologic naïve 40.7% failed both TNFi & VDZ	All received 10mg BID	Week 8 clinical response 60.8% and clinical remission 13.5% Week 16 response 55.4%, remission 48.6% (n=74) Month 6 endoscopic healing 64.9% (n=57)
Lair-Mehiri et al (53)	37 patients with UC	All failed TNFi 97% failed VDZ	All received 10 mg BID	Week 24 colectomy-free survival 77%, clinical response 41%, and corticosteroid-free remission 32%