Table 2.

Summary of treatment-emergent adverse events [safety population].^a

Treatment in OLE:	Etrasimod 2 mg				Placebo
Treatment in DB study:	Placebo [n = 42]	Etrasimod 1 mg [n = 38]	Etrasimod 2 mg [n = 32]	Overall [n = 112]	Total [n = 6]b
Patients with ≥ 1 TEAE, n [%]	25 [59.5]	25 [65.8]	17 [53.1]	67 [59.8]	5 [83.3]
Number of TEAEs	111	85	56	252	22
Number of TEAEs, excluding TEAE of worsening UCc	105	77	47	229	21
Patients with TEAEs leading to death, n	0	0	0	0	0
Patients with TEAEs leading to study discontinuation, n [%]	4 [9.5]	2 [5.3]	4 [12.5]	10 [8.9]	1 [16.7]
Ulcerative colitis—worseningc	2 [4.8]	2 [5.3]	4 [12.5]	8 [7.1]	1 [16.7]
Atrial fibrillation	1 [2.4]	0	0	1 [0.9]	0
Headache	1 [2.4]	0	0	1 [0.9]	0
Patients with serious TEAEs, n [%] [no. of events]d	4 [9.5] [11]	0	3 [9.4]	7 [6.3] [14]	0
Gastrointestinal disorders	2 [4.8] [5]	0	1 [3.1]	3 [2.7] [6]	0
Ulcerative colitis—worseninge	2 [4.8]	0	1 [3.1]	3 [2.7]	0
Pancreatitis	1 [2.4]	0	0	1 [0.9]	0
Large intestine perforation	1 [2.4]	0	0	1 [0.9]	0
Blood and lymphatic system disorders	0	0	2 [6.3]	2 [1.8]	0
Iron-deficiency anaemia	0	0	2 [6.3]	2 [1.8]	0
Infections and infestations	1 [2.4] [2]	0	0	1 [0.9] [2]	0
Gastroenteritis	1 [2.4] [2]	0	0	1 [0.9] [2]	0
Renal and urinary disorders	1 [2.4]	0	0	1 [0.9]	0
Cystitis, haemorrhagic	1 [2.4]	0	0	1 [0.9]	0
Nervous system disorders	2 [4.8]	0	0	2 [1.8]	0
Fine motor skill dysfunction	1 [2.4]	0	0	1 [0.9]	0
Transient ischaemic attack	1 [2.4]	0	0	1 [0.9]	0
Cardiac disorders	1 [2.4]	0	0	1 [0.9]	0
Atrial fibrillation	1 [2.4]	0	0	1 [0.9]	0
Severity [all TEAEs], n [%] [no. of events]d,f
Grade 1—mild	18 [42.9] [44]	17 [44.7] [46]	10 [31.3] [19]	45 [40.2] [109]	4 [66.7] [9]
Grade 2—moderate	20 [47.6] [59]	23 [60.5] [38]	12 [37.5] [32]	55 [49.1] [129]	5 [83.3] [13]
Grade 3—severe	5 [11.9] [8]	1 [2.6]	5 [15.6]	11 [9.8] [14]	0
Grade 4—life-threatening	0	0	0	0	0
Grade 5—death related to TEAE	0	0	0	0	0
Severity [treatment-related TEAEs], n [%] [no. of events]d,f,g
Grade 1—mild	6 [14.3] [9]	3 [7.9]	1 [3.1] [2]	10 [8.9] [14]	0
Grade 2—moderate	8 [19.0] [12]	1 [2.6]	2 [6.3]	11 [9.8] [15]	1 [16.7]
Grade 3—severe	0	0	1 [3.1]	1 [0.9]	0
Grade 4—life-threatening	0	0	0	0	0
Grade 5—death related to TEAE	0	0	0	0	0
TEAE relation to study drug, n [%] [no. of events]d,f,g
Not related	24 [57.1] [90]	25 [65.8] [81]	17 [53.1] [51]	66 [58.9] [222]	5 [83.3] [21]
Related	9 [21.4] [21]	3 [7.9] [4]	4 [12.5] [5]	16 [14.3] [30]	1 [16.7]
Treatment-related TEAEs of special interest, n [%]f,g
Atrioventricular block first degree [grade 1 severity]	1 [2.4]	0	0	1 [0.9]	0

The overall group includes patients who received any treatment [placebo, etrasimod 1 mg, or etrasimod 2 mg] during the DB period.

AE, adverse event; DB, double-blind; OLE, open-label extension; TEAE, treatment-emergent AE; UC, ulcerative colitis.

^aTEAEs were defined as any AE that occurred after the first dose of study medication in the OLE, including any AEs that started in the DB study and were ongoing, worsened, or ended in the OLE. Events were coded using the Medical Dictionary for Regulatory Activities, version 20.1.

^bOf the six patients who received placebo in the OLE, in the DB study two received placebo, one received etrasimod 1 mg, and three received etrasimod 2 mg.

^cIncludes ‘colitis ulcerative’ and ‘colitis’.

^dAt each level of patient summarisation, a patient was counted once if the patient reported one or more events. Unless otherwise indicated, the number of events = the number of patients.

^eIncludes ‘colitis ulcerative’, ‘colitis’, and ‘proctitis ulcerative’.

^fSeverity of TEAEs was assessed by investigator and graded according to the US National Cancer Institute Common Terminology Criteria for Adverse Events [Version 4.03] definitions. At each level of patient summarisation, a patient was counted once for the most severe event.

^gRelatedness was determined by investigator judgement.