Table 2.

Summary of novel therapies targeting IL-23 and the IL-23R signalling pathway in ulcerative colitis. Summary of novel therapies targeting IL-23 and its downstream signalling pathway with details of key phase 2 and phase 3 studies in ulcerative colitis [shaded area indicates phase 2 and 3 studies currently in progress or not yet reported in full]

Target	Drug	Evidence	Number of included patients	Sex and age range of included patients	Summary of primary outcomes, or anticipated primary outcomes if not yet reported	Reference or Clinicaltrials.gov identifier
Shared IL-12/IL-23 p40 subunit	Ustekinumab	Phase 3 randomized placebo-controlled trials [UNIFI study].	n = 961 [induction study] n = 523 [maintenance study]	Induction trial: M/F n = 582/379 Mean age: 41.2 years [placebo] 42.2 years [130 mg group] 41.7 years [6 mg/kg group] Maintenance trial: M/F n = 297/226 Mean age: 42.0 years [placebo] 40.7 years [12 weekly group] 39.5 years [8 weekly group]	Induction trial: clinical remission significantly higher after 8 weeks of treatment [15.6%, 130 mg group and 15.5%, 6 mg/kg group] compared to placebo [5.3%]. Maintenance trial: significantly enhanced rate of clinical remission after 44 weeks [in 8 and 12-weekly treatment arms] compared to placebo.	Sands et al. N Engl J Med 2019;381:1201–14
IL-23 p19 subunit	Mirikizumab	Phase 2 randomized placebo-controlled trial	n = 249	M/F n = 149/100 Mean age: 42.6 years [placebo] 41.8 years [50mg] 43.4 years [200 mg] 42.4 years [600 mg]	Clinical remission after 12 weeks of treatment compared to placebo—difference not statistically significant.	Sandborn et al. Gastroenterology 2020;158:537–49 e10
IL-23 p19 subunit	Mirikizumab	Phase 3 randomized placebo-controlled trial [LUCENT 1, LUCENT 2]	Estimated ~ 1160 participants [NCT03518086] Estimated ~1044 participants [NCT03524092]		Clinical remission [determined using modified Mayo score] after 12 weeks of treatment [LUCENT 1]. Clinical remission after 40 weeks of treatment [LUCENT 2].	NCT03518086 NCT03524092
	Risankizumab	Phase 3 randomized placebo-controlled study	Estimated ~942 participants		Percentage of participants achieving clinical remission at week 52 [determined using adapted Mayo score].	NCT03398135
	Guselkumab	Phase 2b/3 randomized placebo-controlled trial [QUASAR]	Estimated ~1000 participants		Clinical response [induction study 1] after 12 weeks of treatment Clinical remission [induction study 2]. Clinical remission after 44 weeks of treatment [maintenance study].	NCT04033445
	Brazikumab	Phase 2 study	Estimated ~256 participants		Clinical remission [defined by modified Mayo score] after 10 weeks of treatment.	NCT03616821
JAK1/TYK2	Brepocitinib	Phase 2b randomized, placebo-controlled study	Estimated ~319 participants		Total Mayo score of participants after 8 weeks of treatment.	NCT02958865
TYK2	Deucravacitinib	Phase 2 randomized, placebo-controlled trial	Estimated ~131 participants		Clinical remission according to modified Mayo score following 12 weeks of treatment.	NCT03934216