Evaluating tofacitinib citrate in the treatment of moderate-to-severe active ulcerative colitis: design, development and positioning of therapy

Figures & data

Figure 1 JAK-STAT pathway. The JAK-STAT pathway involves of 1) cytokines which can include interleukins, interferon, granulocyte-macrophage colony stimulating factor 2) cytokine receptors 3) JAKs (JAK1-3, TYK2) and 4) STATs (STAT1-6).

Table 1 Tofacitinib as induction therapy in ulcerative colitis

Phase/study	Treatment	Size	Clinical response at 8 weeks, % (p)	Clinical remission at 8 weeks, % (p)	Endoscopic response at 8 weeks, % (p)	Mucosal healing at 8 weeks, % (p)	Endoscopic remission at 8 weeks, % (p)
Phase II Induction Sandborn et al 2012	Placebo 0.5 mg BID 3 mg BID 10 mg BID 15 mg BID	48 31 33 33 49	42% 32% (p=0.39) 48% (p=0.55) 61% (p=10) 78% (p<0.001)	10% 13% (p=0.76) 33% (p=0.01) 48% (p<0.001) 41% (p<0.001)	46% 52% (p=0.64) 58% (p-0.30) 67% (p=0.07) 78% (p=0.001)	Not available	2% 10% (0.14) 18% (p=0.01) 30% (p<0.001) 27% (p<0.001)
Phase III OCTAVE 1 Induction Sandborn et al 2017	Placebo 10 mg BID 15 mg BID	122 476 16	32.8% 59.9% (p<0.001) 87.5% (NA)	8.2% 18.5% (p=0.007) 43.8% (NA)	Not available	15.6% 31.3% (p<0.001) 62.5% (NA)	1.6% 6.7% (p=0.04) 12.5% (NA)
Phase III OCTAVE 2 Induction Sandborn et al 2017	Placebo 10 mg BID 15 mg BID	112 429 6	28.6% 55.0% (p<0.001) 83.3% (NA)	3.6% 16.6% (p<0.001) 50.0% (NA)	Not available	11.6% 28.4% (p<0.001) 50.0% (NA)	1.8% 7.0% (p=0.04) 0% (NA)

Abbreviations: BID, twice daily; NA, not applicable.

Table 2 Tofacitinib as maintenance therapy in ulcerative colitis

Phase/study	Treatment	Size	Clinical remission	healing at 52 weeks	Sustained and glucocorticoid-free remission	Sustained mucosal healing among patients with mucosal healing at baseline
Phase III OCTAVE Sustain Sandborn et al 2017	Placebo 5 mg BID 10 mg BID	198 198 197	11.1% 34.3% (p<0.001) 40.6% (p<0.001)	13.1% 37.4% (p<0.001) 45.7% (p<0.001)	5.1% 35.4% (p<0.001) 47.3% (p<0.001)	8.9% 33.3% (p<0.001) 49.4% (p<0.001)

Abbreviation: BID, Twice daily.

Table 3 Tofacitinib as induction therapy in Crohn’s disease

Phase/study	Treatment	Size	Clinical response	Clinical remission
Phase II Sandborn et al 2014	Placebo 1 mg BID 5 mg BID 15 mg BID	34 36 34 35	47% 36% (p=0.467) 58% (p=0.466) 46% (p≥0.999)	21% 31% (p=0.417) 24% (p=0.776) 14% (p=0.540)
Phase IIb Induction Panés et al 2017	Placebo 5 mg BID 10 mg BID	91 86 86	62% 76.5% (p<0.05) 74.4% (p>0.05)	36.7% 43% (0.325) 43% (0.392)

Abbreviation: BID, twice daily.

Table 4 Tofacitinib safety profile in inflammatory bowel disease

	Sandborn et al (2012)	OCTAVE 1 Sandborn et al 2017	OCTAVE 2 Sandborn et al 2017	OCTAVE Sustain Sandborn et al 217	Sandborn et al (2014)	Panés et al induction (2017)	Panés et al maintenance (2017)
Treatment	Placebo 0.5 mg BID 3 mg BID 10 mg BID 15 mg BID	Placebo 10 mg BID	Placebo 10 mg BID	Placebo 5 mg BID 10 mg BID	Placebo 1 mg BID 5 mg BID 15 mg BID	Placebo 5 mg BID 10 mg BID	Placebo 5 mg BID 10 mg BID
Disease	UC	UC	UC	UC	CD	CD	CD
No. AE, n (%)	23 (48) 19 (61) 11 (33) 14 (42) 20 (41)	73 (59.8) 269 (56.5)	59 (52.7) 232 (54.1)	149 (75.3) 143 (72.2) 156 (79.6)	22 (64.7) 18 (50.0) 21 (61.8) 22 (62.9)	55 (60.4) 50 (58.1) 52 (60.5)	44 (74.6) 50 (83.3) 48 (78.7)
Serious AE, n (%)	4 (8) 1 (3) 1 (3) 2 (6) 2 (4)	5 (4.1) 16 (3.4)	9 (8.0) 18 (4.2)	13 (6.6) 10 (5.1) 11 (5.6)	5 (14.7) 4(11.1) 4 (11.8) 1 (2.9)	3 (3.3) 3 (3.5) 10 (11.6)	7 (11.6) 6 (10.0) 8 (13.1)
Infectious AE, n (%)	7 (15) 8 (26) 3 (9) 9 (27) 3 (6)	19 (15.6) 111 (23.3)	17 (15.2) 78 (18.2)	48 (24.2) 71 (35.9) 78 (39.8)	8 (23.5) 5 (13.9) 8 (23.5) 5 (14.3)	Not reported	Not reported
Serious infection, n (%)	0 (0) 0 (0) 0 (0) 2 (6) 0 (0)	0 (0) 6 (1.3)	0 (0) 1 (0.2)	2 (1.0) 2 (1.0) 1 (0.5)	4 (11.7) 0 (0) 1 (0.03) 0 (0)	2 (2.2) 2 (2.3) 2 (2.3)	0 (0) 3 (0.05) 2 (3.2)
Discontinuation due to AE, n (%)	4 (8) 2 (6) 0 (0) 1 (3) 2 (4)	2 (1.6) 18 (3.8)	8 (7.1) 17 (4.0)	37 (18.7) 19 (9.1) 19 (9.7)	3 (8.8) 1 (2.8) 1 (2.9) 1 (2.9)	5 (5.5) 3 (3.5) 8 (9.3)	3 (5.1) 7 (11.7) 6 (9.8)

Abbreviations: AE, Adverse events; BID, twice daily; UC, ulcerative colitis; CD, Crohn’s disease.