Table 2.

Safety in the True North parent study and the True North OLE in patients on continuous ozanimod who entered the OLE in clinical response.^a

	Week 52 clinical responders [n = 131] Total PYb = 433.9
	n [%]	EAIR per 100 PYc
TEAEs	109 [83.2]	73.6
Serious TEAEs	24 [18.3]	6.1
TEAEs leading to treatment discontinuation	8 [6.1]	1.9
Herpes zoster	2 [1.5]	0.5
Lung neoplasm malignant	1 [0.8]	0.2
Lymphopenia	1 [0.8]	0.2
Idiopathic intracranial hypertension	1 [0.8]	0.2
Abdominal pain	1 [0.8]	0.2
Frequent bowel movementsd	1 [0.8]	0.2
Rectal haemorrhaged	1 [0.8]	0.2
Ovarian cyst	1 [0.8]	0.2
Sudden deathe	1 [0.8]	0.2
Most frequent TEAEs [occurring in ≥5% of patients]f
Lymphopeniag	21 [16.0]	5.4
COVID-19h	17 [13.0]	4.0
Arthralgia	17 [13.0]	4.3
Hypertensioni	16 [12.2]	3.9
Headache	15 [11.5]	3.7
Lymphocyte count decreasedg	14 [10.7]	3.4
Nasopharyngitis	13 [9.9]	3.2
Alanine aminotransferase increasedg	13 [9.9]	3.2
Anemiaf	12 [9.2]	3.0
Gamma-glutamyl transferase increasedg	11 [8.4]	2.7
Back pain	9 [6.9]	2.1
Sinusitis	9 [6.9]	2.2
Upper respiratory tract infection	7 [5.3]	1.7
Herpes zoster	7 [5.3]	1.7
Infection [occurring in ≥3% of patients]j	68 [51.9]	24.3
COVID-19	17 [13.0]	4.0
Nasopharyngitis	13 [9.9]	3.2
Sinusitis	9 [6.9]	2.2
Serious infection	8 [6.1]	1.9
Upper respiratory tract infection	7 [5.3]	1.7
Herpes zoster	7 [5.3]	1.7
Respiratory tract infection viral	6 [4.6]	1.4
Bronchitis	6 [4.6]	1.4
Influenza	4 [3.1]	0.9
Gastroenteritis	4 [3.1]	0.9
Malignancies	3 [2.3]	0.7
Basal cell carcinoma	2 [1.5]	0.5
Lung neoplasm malignant	1 [0.8]	0.2
AEs of special interest
Bradycardiak	1 [0.8]	0.2
Complete atrioventricular blockl	1 [0.8]	0.2
Macular oedema	1 [0.8]	0.2

AE, adverse event; EAIR, exposure-adjusted incidence rate; OLE, open-label extension; PY, patient-years; TEAE, treatment-emergent adverse event.

^aData were collected from the beginning of the True North parent study until data cutoff for this analysis [January 10, 2022].

^bTotal PY was defined as the sum of the number of years on study contributed by each patient from time of first dose to last date on study.

^cEAIRs were calculated as number of patients/PY × 100.

^dFrequent bowel movements and rectal haemorrhage occurred in the same patient.

^eThe cause and circumstances were unclear; this was considered as ‘unlikely’ to be related to ozanimod.

^fThe most frequent events were defined as those that occurred in ≥5% of patients.

^gLaboratory values were flagged by the central laboratory if they fell outside the standard reference range; investigators decided whether laboratory values qualified as AEs. Laboratory values that qualified as AEs are reported in this table.

^hNo COVID-19 events occurred during the 52-week True North study, as the study had closed prior to the pandemic.

ⁱOf the 16 patients with hypertension, 15 had elevated systolic and/or diastolic blood pressure at baseline and one was normotensive. All cases of hypertension were manageable without a need for ozanimod treatment interruption or discontinuation. All cases of hypertension were nonserious [11/16 were of mild intensity and 5/16 were of moderate intensity], and most [15/16] were considered unrelated to ozanimod.

^jThe most frequent events were defined as those that occurred in ≥3% of patients.

^kThe case of bradycardia occurred on Day 1 of the True North induction period, was considered mild and nonserious, did not require treatment interruption or hospitalisation, and resolved on Day 7.

^lOne patient on ozanimod for 3 years developed an atrioventricular block that was thought to be related to atherosclerotic disease around the cardiac conduction system.