Novel oral-targeted therapies for mucosal healing in ulcerative colitis

Table 1 Summary of treatment results with Janus kinase inhibitors in ulcerative colitis patients

Study	Drug	Study population	Treatment arm	Endoscopy endpoint	Time of observation, wk	Rate of mucosal healing
Sandborn et al[28]	Tofacitinib	Moderate to severe UC patients (n = 194)	Doses of 0.5, 3, 10, or 15 mg/twice daily vs placebo for 8 wk	Secondary end points; Endoscopic remission: an endoscopic subscore of 0	At 8 wk	Placebo 2%
						Tofacitinib 0.5 mg = 10%, (P = 0.14)
						Tofacitinib 3 mg = 18%, (P = 0.01)
						Tofacitinib 10 mg = 30%, (P < 0.001),
						Tofacitinib 15 mg = 27%, (P < 0.001)
Sandborn et al[30]	Tofacitinib	Moderate to severe UC patients (n = 614)	Dose of 10 mg/ twice daily vs placebo for 8 wk 16 patients received tofacitinib 15 mg twice daily	Key secondary endpoint was MH (Mayo endoscopic subscore of 0 or 1)	At 8 wk	Placebo 15.6%
						Tofacitinib 10 mg = 31.3%, (P < 0.001)
Sandborn et al[30]	Tofacitinib	Moderate to severe UC patients (n = 547)	Dose of 10 mg twice daily vs placebo for 8 wk; 6 received tofacitinib; 15 mg twice daily	Key secondary endpoint was MH; Mayo endoscopic subscore of 0 or 1	At 8 wk	Placebo 11.6%
						Tofacitinib 10 mg = 28.4%, (P < 0.001)
Sandborn et al[30]	Tofacitinib	Moderate to severe UC patients (n = 593)	Dose of 5 mg twice daily, 10 mg twice daily, or placebo for 52 wk	Key secondary end points were mucosal healing; Mayo endoscopic subscore of 0 or 1	At 52 wk	Placebo 13.1%
						Tofacitinib 5 mg = 37.4%, (P < 0.001)
						Tofacitinib 10 mg = 45.7%, (P < 0.001)
Motoya et al[31]	Tofacitinib	Moderate to severe UC patients (n = 121 OCTAVE Induction 1 and 2) (n = 63, OCTAVE Sustain)	Dose of 5 mg twice daily (OCTAVE sustain only), 10 mg twice daily, or placebo	Key secondary endpoint was MH (Mayo endoscopic subscore of 0 or 1	At 8 wk (OCTAVE Induction 1 and 2); At 52 wk (OCTAVE sustain)	Placebo 7.7%
						Tofacitinib 10 mg = 24.2% (OCTAVE Induction 1 and 2)
						Placebo 20%
						Tofacitinib 5 mg = 45.5%
						Tofacitinib 10 mg = 57.1% ( OCTAVE Sustain)
Sands et al[35]	Peficitinib	Moderate-to-severe UC (n = 219)	Dose of 25 mg once daily (qd), 75 mg qd, 150 mg qd, 75 mg twice daily (bid) or placebo	Secondary endpoint was MH; Mayo endoscopic subscore of 0 or 1	At 8 wk	Placebo 18.6%
						Peficitinib 25 mg qd mg = 20.5%
						Peficitinib 75 mg qd = 29.5%
						Peficitinib 150 mg qd = 45.5% (P < 0.05)
						Peficitinib 75 mg bidmg = 36.4%

UC: Ulcerative colitis; OCTAVE: Oral Clinical Trials for tofAcitinib in ulceratiVE colitis.

Table 2 Summary of treatment results with sphingosine-1-phosphate receptor modulators, AJM300, and phospholipids in ulcerative colitis patients

Study	Drug	Study population	Treatment arm	Endoscopy endpoint	Time of observation, wk	Rate of mucosal healing
Sandborn et al[41]	Ozanimod	Moderate to severe UC patients (n = 197)	Dose of 0.5 mg or 1 mg or placebo, once daily	Mcosal healing (endoscopy subscore ≤ 1)	At 8 wk; at 32 wk	Placebo 12%
						Ozanimod 0.5 mg = 28%, (P = 0.03)
						Ozanimod 1 mg = 34%, (P = 0.002)
						At week 8
						Placebo 12%
						Ozanimod 0.5 mg = 32%, (P = 0.006)
						Ozanimod 1 mg = 33%, (P = 0.005)
						At week 32
Yoshimura et al[46]	AJM300	Moderate to severe UC patients (n = 102)	Dose of 960 mg or placebo, 3 times daily	Mucosal healing, (endoscopic subscore of 0 or 1)	At 8 wk	Placebo 29.4%
						AJM300 960 mg = 58.8% (P = 0.0014)
Stremmel et al[50]	Phosphatidylcholine-rich phospholipids	Chronic active, ulcerative colitis, with a clinical activity index (CAI) of > 4 (n = 60)	Dose of PC rich phospholipids (1.5 g /dose) or placebo, four times daily	Mucosal healing, was not formally assessed 48 patients were examined using the standard endoscopic activity index (EAI); Secondary end point analysis DEAI (> 50%)	At three mo	None of 29 placebo patients DEAI (> 50%) in 11 of 29 evaluated of PC patients P = 0.00016
Karner et al[51]	LT-02	Ulcerative colitis patients with an inadequate response to mesalazine, a disease activity score (Simple Clinical Colitis Activity Index (SCCAI)) of ≥ 5, and bloody diarrhea (n = 156)	Dose of LT-2 (0.8, 1.6 or 3.2 g) or placebo	Mucosal healing (endoscopic Mayo Score ≤ 1)	At 12 wk	Placebo 40.0%
						LT-2 0.8 g = 57.5%, (P = 0.097)
						LT-2 1.6 g = 56.1%, (P = 0.097)
						LT-2 3.2 g = 51.4%, (P = 0.097)
						Pooled LT-02 groups 55.2 (P = 0.098)

UC: Ulcerative colitis; OCTAVE: Oral Clinical Trials for tofAcitinib in ulceratiVE colitis.