Inclusion Criteria:
* Male or female aged ≥ 18 years (verified at screening)
* Ability to provide written informed consent and to be compliant with protocol assessments (verified at screening)
* Diagnosed with UC and underwent TPC with IPAA for medically refractory disease or dysplasia (verified at screening)
* Screening may take place at any time from one month to two years after the final surgical stage
* High-risk of developing acute pouchitis - defined as fulfilling at least one of the criteria defined in section 2 (verified at screening)
* Patients with 1 prior episode of acute pouchitis can be enrolled - after a minimum period of 4 weeks after completion of a course of antibiotics and resolution of symptoms of pouchitis
* Symptomatic remission defined by a symptom mPDAI subscore ≤2 points at the baseline visit (verified at screening, baseline)
* Adequate hematological function defined by white blood cell count ≥ 3.5 × 109/L with absolute neutrophil count (ANC) ≥ 1.5 × 109/L, absolute lymphocyte count (ALC) ≥ 0.8 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 8 g/dL (verified at screening)
* Healthcare professional-confirmed history of varicella or a full course of vaccination against varicella zoster virus (VZV) or a positive antibody test to VZV (verified at screening)
* 12-lead electrocardiogram (ECG) that showed no clinically significant abnormalities as defined by the clinician's judgement (verified at screening)
* Females must be non-pregnant, as determined by qualitative urine hCG testing, non-lactating, and if premenopausal, must agree to using a highly effective contraception method (that can achieve a failure rate of less than 1% per year when used consistently and correctly) during treatment and for one week after stopping treatment with etrasimod (verified at screening)
Exclusion Criteria:
* Isolated cuffitis (verified at screening pouchoscopy)
* Diagnosis of Crohn's disease (verified at screening)
* Diagnosis of Crohn's disease-like pouch inflammation (verified at screening)
o Crohn's disease-like pouch inflammation is defined as ulcerations of the pre-pouch ileum extending \> 10 cm above the inlet, strictures in the pre-pouch ileum or pouch body outside of the anastomoses, and/or fistulae of the pre-pouch ileum, pouch body, or perineum
* Diagnosis of chronic pouchitis (verified at screening)
o Chronic pouchitis is defined as persistent (\> 4 weeks) or recurrent (\> 4 episodes/year) symptoms of pouchitis
* Anastomotic stenosis or other mechanical complications of the pouch (verified at screening pouchoscopy)
* Treatment with probiotics ≤ 3 months prior to screening (verified at screening)
* Treatment with topical rectal 5-ASA, or steroids ≤ 2 weeks prior to or during screening (verified at screening)
* Any use of a biologic or small molecule approved for moderately to severely active UC or investigational, after TPC with IPAA (verified at screening)
* Any prior exposure to a S1P receptor modulator therapy, at any time (verified at screening)
* Any investigational or biologic agent within 30 days of screening pouchoscopy (verified at screening)
* Have the following cardiovascular history (verified at screening):
* In the last 6 months, have experienced a myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III or IV heart failure
* Have a history or presence of Mobitz type II second-degree or third-degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker
* A history of symptomatic bradycardia, recurrent cardiogenic syncope, Mobitz type I second-degree AV block, or severe untreated sleep apnea
* Significant QT prolongation (QTcF interval ≥ 450 ms in male or ≥ 470 ms in females)
* Arrhythmias requiring treatment with Class Ia or Class III anti-arrhythmic drugs or QT prolonging drugs
* Clinically significant or serious active infection ≤ 28 days prior to baseline - including but not limited to (verified at screening):
* Positive assay or stool culture for pathogens (ova and parasite examination, bacteria) or
* positive test for Clostridioides difficile toxin at screening
* Active tuberculosis
* Acute or chronic hepatitis B or hepatitis C
* HIV infection
* Pregnancy, lactation, or a positive urine pregnancy test measured during screening
* Severe hepatic impairment (Child Pugh Class C) (verified at screening)
* Have a known history of macular edema or retinopathy (verified at screening)
* History of cancer within the last 5 years (excluding in situ squamous or basal cell carcinoma of the skin that has been excised and resolved) or current malignancy (verified at screening)
* History of posterior reversible encephalopathy syndrome (PRES)
* Have a history of any clinically significant medical condition that, in the investigator's opinion, precludes participation in the study (verified at screening)
