World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://wjon.elmerpub.com

Original Article

Volume 17, Number 4, August 2026, pages 534-546

Comprehensive Analysis of Ozanimod-Related Adverse Events Based on the FAERS Database

↓ **Table 1.** Four Grid Table
	Target AEs	Non-target AEs	Total
AE: adverse event.
Ozanimod	a	b	a + b
Non-ozanimod	c	d	c + d
Total	a + c	b + d	N = a + b + c + d

↓ Table 1. Four Grid Table

Target AEs

Non-target AEs

Total

AE: adverse event.

Ozanimod

a + b

Non-ozanimod

c + d

Total

a + c

b + d

N = a + b + c + d

↓ **Table 2.** ROR, PRR, BCPNN, and EBGM Methods, Formulas, and Thresholds
Method	Formula	Threshold
BPNN: Bayesian Confidence Propagation Neural Network; CI: confidence interval; EBGM: Empirical Bayesian Geometric Mean; IC: information component; PRR: proportional reporting ratio; ROR: reporting odds ratio.
ROR	$\begin{array}{l} ROR = \frac{a / c}{b / d} = \frac{a d}{b c} \\ SE(lnROR) = \sqrt{\frac{1}{a} + \frac{1}{b} + \frac{1}{c} + \frac{1}{d}} \\ 95% CI = e^{ln(ROR) \pm 1.96 \sqrt{\frac{1}{a} + \frac{1}{b} + \frac{1}{c} + \frac{1}{d}}} \end{array}$	a ≥ 3 and 95% CI (lower limit) > 1
PRR	$\begin{array}{l} PRR = \frac{a / (a + b)}{c / (c + d)} \\ SE (lnPRR) = \sqrt{\frac{1}{a} - \frac{1}{a + b} + \frac{1}{c} - \frac{1}{c + d}} \\ 95% CI = e^{ln(PRR) \pm 1.96 \sqrt{\frac{1}{a} - \frac{1}{a + b} + \frac{1}{c} - \frac{1}{c + d}}} \end{array}$	a ≥ 3 and 95% CI (lower limit) > 1
BCPNN	$\begin{array}{l} IC = {log}_{2} \frac{p (x, y)}{p (x) p (y)} = {log}_{2} \frac{a (a + b + c + d)}{(a + b) (a + c)} \\ E(IC) = {log}_{2} \frac{(a + γ 11) (a + b + c + d + α) (a + b + c + d + β)}{(a + b + c + d + γ) (a + b + α 1) (a + c + β 1)} \\ V(IC) = \frac{1}{{(ln2)}^{2}} {\begin{cases} [\frac{(a + b + c + d) - a + γ - γ 11}{(a + γ 11) (1 + a + b + c + d + γ)}] \\ + [\frac{(a + b + c + d) - (a + b) + α - α 1)}{(a + b + α 1) (1 + a + b + c + d + α)}] \\ + [\frac{(a + b + c + d) - (a + c) + β - β 1)}{(a + c + β 1) (1 + a + b + c + d + β)}] \end{cases}} \\ γ = γ 11 \frac{(a + b + c + d + α) (a + b + c + d + β)}{(a + b + α 1) (a + c + β 1)} \\ I C - 2 S D = E (I C) - 2 \sqrt{V (I C)} \end{array}$	IC025 > 0
EBGM	$\begin{array}{l} EBGM = \frac{a (a + b + c + d)}{(a + c) (a + b)} \\ 95% CI = e^{ln(EBGM) \pm 1.96 \sqrt{\frac{1}{a} + \frac{1}{b} + \frac{1}{c} + \frac{1}{d}}} \end{array}$	EBGM05 > 2

↓ Table 2. ROR, PRR, BCPNN, and EBGM Methods, Formulas, and Thresholds

Method

Formula

Threshold

BPNN: Bayesian Confidence Propagation Neural Network; CI: confidence interval; EBGM: Empirical Bayesian Geometric Mean; IC: information component; PRR: proportional reporting ratio; ROR: reporting odds ratio.

ROR

\begin{array}{l} ROR = \frac{a / c}{b / d} = \frac{a d}{b c} \\ SE(lnROR) = \sqrt{\frac{1}{a} + \frac{1}{b} + \frac{1}{c} + \frac{1}{d}} \\ 95% CI = e^{ln(ROR) \pm 1.96 \sqrt{\frac{1}{a} + \frac{1}{b} + \frac{1}{c} + \frac{1}{d}}} \end{array}

a ≥ 3 and 95% CI (lower limit) > 1

PRR

\begin{array}{l} PRR = \frac{a / (a + b)}{c / (c + d)} \\ SE (lnPRR) = \sqrt{\frac{1}{a} - \frac{1}{a + b} + \frac{1}{c} - \frac{1}{c + d}} \\ 95% CI = e^{ln(PRR) \pm 1.96 \sqrt{\frac{1}{a} - \frac{1}{a + b} + \frac{1}{c} - \frac{1}{c + d}}} \end{array}

a ≥ 3 and 95% CI (lower limit) > 1

BCPNN

\begin{array}{l} IC = {log}_{2} \frac{p (x, y)}{p (x) p (y)} = {log}_{2} \frac{a (a + b + c + d)}{(a + b) (a + c)} \\ E(IC) = {log}_{2} \frac{(a + γ 11) (a + b + c + d + α) (a + b + c + d + β)}{(a + b + c + d + γ) (a + b + α 1) (a + c + β 1)} \\ V(IC) = \frac{1}{{(ln2)}^{2}} {\begin{cases} [\frac{(a + b + c + d) - a + γ - γ 11}{(a + γ 11) (1 + a + b + c + d + γ)}] \\ + [\frac{(a + b + c + d) - (a + b) + α - α 1)}{(a + b + α 1) (1 + a + b + c + d + α)}] \\ + [\frac{(a + b + c + d) - (a + c) + β - β 1)}{(a + c + β 1) (1 + a + b + c + d + β)}] \end{cases}} \\ γ = γ 11 \frac{(a + b + c + d + α) (a + b + c + d + β)}{(a + b + α 1) (a + c + β 1)} \\ I C - 2 S D = E (I C) - 2 \sqrt{V (I C)} \end{array}

IC025 > 0

EBGM

\begin{array}{l} EBGM = \frac{a (a + b + c + d)}{(a + c) (a + b)} \\ 95% CI = e^{ln(EBGM) \pm 1.96 \sqrt{\frac{1}{a} + \frac{1}{b} + \frac{1}{c} + \frac{1}{d}}} \end{array}

EBGM05 > 2

↓ **Table 3.** Basic Information on AEs Related to Ozanimod
Factors	Number of events (%)
AE: adverse event.
Gender
Female	4,945 (67.7%)
Male	2,014 (27.6%)
Unknown	346 (4.7%)
Age
< 18	50 (0.7%)
18–64.9	4,930 (67.5%)
65–85	829 (11.3%)
> 85	17 (0.2%)
Reporter
Consumer	2,637 (36.1%)
Health professional	3,552 (48.6%)
Physician	940 (12.9%)
Pharmacist	153 (2.1%)
Reported countries
United States	6,794 (93.0%)
Germany	185 (2.5%)
Poland	41 (0.6%)
Russia	30 (0.4%)
Italy	30 (0.4%)
Report year
2020	214 (2.9%)
2021	1,956 (26.8%)
2022	1,724 (23.6%)
2023	1,518 (20.8%)
2024	1,542 (21.1%)
2025	351 (4.8%)
Serious outcomes
Death	75 (1.0%)
Disability	54 (0.7%)
Hospitalization	570 (7.8%)
Life-threatening	67 (0.9%)
AE occurrence time to medication date (days)
0–30	602 (8.2%)
31–60	179 (2.5%)
61–90	144 (2.0%)
91–120	105 (1.4%)
121–150	68 (0.9%)
151–180	68 (0.9%)
181–360	218 (3.0%)
> 360	223 (3.1%)

↓ Table 3. Basic Information on AEs Related to Ozanimod

Factors

Number of events (%)

AE: adverse event.

Gender

Female

4,945 (67.7%)

Male

2,014 (27.6%)

Unknown

346 (4.7%)

Age

< 18

50 (0.7%)

18–64.9

4,930 (67.5%)

65–85

829 (11.3%)

> 85

17 (0.2%)

Reporter

Consumer

2,637 (36.1%)

Health professional

3,552 (48.6%)

Physician

940 (12.9%)

Pharmacist

153 (2.1%)

Reported countries

United States

6,794 (93.0%)

Germany

185 (2.5%)

Poland

41 (0.6%)

Russia

30 (0.4%)

Italy

30 (0.4%)

Report year

2020

214 (2.9%)

2021

1,956 (26.8%)

2022

1,724 (23.6%)

2023

1,518 (20.8%)

2024

1,542 (21.1%)

2025

351 (4.8%)

Serious outcomes

Death

75 (1.0%)

Disability

54 (0.7%)

Hospitalization

570 (7.8%)

Life-threatening

67 (0.9%)

AE occurrence time to medication date (days)

0–30

602 (8.2%)

31–60

179 (2.5%)

61–90

144 (2.0%)

91–120

105 (1.4%)

121–150

68 (0.9%)

151–180

68 (0.9%)

181–360

218 (3.0%)

> 360

223 (3.1%)

↓ **Table 4.** Disproportionality Analysis of Ozanimod-Related AE Reports at the SOC Level
System organ class	Case reports	ROR (95% CI)	PRR (χ²)	EBGM (EBGM05)	IC (IC025)
A positive signal was defined as meeting the predefined criteria of report count ≥ 3, lower limit of ROR 95% CI > 1, lower limit of PRR 95% CI > 1, EBGM05 > 2, and IC025 > 0. AE: adverse event; CI: confidence interval; EBGM: empirical Bayesian geometric mean; IC: information component; PRR: proportional reporting ratio; PT: Preferred Term; ROR: reporting odds ratio; SOC: System Organ Class.
General disorders and administration site conditions	3,047	1.1 (1.06–1.15)	1.08 (24.49)	1.08 (1.04)	0.12 (0.06)
Nervous system disorders	2,909	2.9 (2.78–3.02)	2.55 (2,947.53)	2.55 (2.45)	1.35 (1.29)
Gastrointestinal disorders	1,847	1.54 (1.47–1.62)	1.48 (311.11)	1.48 (1.41)	0.56 (0.49)
Investigations	1,084	1.19 (1.12–1.27)	1.18 (30.95)	1.18 (1.11)	0.24 (0.15)
Musculoskeletal and connective tissue disorders	1,045	1.32 (1.24–1.4)	1.3 (74.89)	1.3 (1.22)	1.3 (1.22)
Injury, poisoning, and procedural complications	1,009	0.47 (0.44–0.5)	0.5 (577.24)	0.5 (0.47)	−1 (−1.09)
Infections and infestations	908	1 (0.94–1.07)	1 (0.01)	1 (0.94)	0.01 (−0.09)
Psychiatric disorders	679	0.8 (0.74–0.86)	0.81 (33.06)	0.81 (0.75)	−0.31 (−0.42)
Respiratory, thoracic, and mediastinal disorders	515	0.71 (0.65–0.77)	0.72 (61)	0.72 (0.66)	−0.48 (−0.61)
Skin and subcutaneous tissue disorders	495	0.55 (0.5–0.6)	0.56 (175.44)	0.57 (0.52)	−0.82 (−0.95)
Eye disorders	442	1.43 (1.3–1.57)	1.42 (55.76)	1.42 (1.29)	0.5 (0.36)
Vascular disorders	363	1.25 (1.13–1.39)	1.24 (17.8)	1.24 (1.12)	0.32 (0.16)
Cardiac disorders	242	0.78 (0.69–0.89)	0.79 (14.5)	0.79 (0.69)	−0.35 (−0.53)
Renal and urinary disorders	202	0.71 (0.62–0.81)	0.71 (24.26)	0.71 (0.62)	−0.49 (−0.69)
Blood and lymphatic system disorders	178	0.66 (0.57–0.76)	0.66 (31.88)	0.66 (0.57)	−0.6 (−0.82)
Neoplasms benign, malignant, and unspecified (cysts and polyps)	177	0.29 (0.25–0.33)	0.3 (306.53)	0.3 (0.26)	−1.75 (−1.96)
Metabolism and nutrition disorders	160	0.52 (0.44–0.61)	0.52 (70.41)	0.52 (0.45)	−0.93 (−1.16)
Immune system disorders	119	0.65 (0.54–0.78)	0.65 (22.71)	0.65 (0.54)	−0.62 (−0.88)
Surgical and medical procedures	110	0.45 (0.38–0.55)	0.46 (72.23)	0.46 (0.38)	−1.13 (−1.4)
Reproductive system and breast disorders	72	0.74 (0.59–0.94)	0.74 (6.35)	0.74 (0.59)	−0.43 (−0.76)
Ear and labyrinth disorders	66	1.02 (0.8–1.3)	1.02 (0.04)	1.02 (0.8)	0.03 (−0.32)
Pregnancy, puerperium, and perinatal conditions	63	1.19 (0.93–1.53)	1.19 (1.99)	1.19 (0.93)	0.26 (−0.11)
Social circumstances	60	0.77 (0.6–1)	0.77 (4)	0.77 (0.6)	−0.37 (−0.74)
Hepatobiliary disorders	52	0.39 (0.29–0.51)	0.39 (50.64)	0.39 (0.3)	−1.37 (−1.75)
Product issues	28	0.09 (0.06–0.13)	0.09 (259.85)	0.09 (0.06)	−3.46 (−3.95)
Endocrine disorders	14	0.32 (0.19–0.55)	0.32 (19.8)	0.32 (0.19)	−1.63 (−2.3)
Congenital, familial, and genetic disorders	4	0.11 (0.04–0.28)	0.11 (30.43)	0.11 (0.04)	−3.24 (−4.25)

↓ Table 4. Disproportionality Analysis of Ozanimod-Related AE Reports at the SOC Level

System organ class

Case reports

ROR (95% CI)

PRR (χ²)

EBGM (EBGM05)

IC (IC025)

A positive signal was defined as meeting the predefined criteria of report count ≥ 3, lower limit of ROR 95% CI > 1, lower limit of PRR 95% CI > 1, EBGM05 > 2, and IC025 > 0. AE: adverse event; CI: confidence interval; EBGM: empirical Bayesian geometric mean; IC: information component; PRR: proportional reporting ratio; PT: Preferred Term; ROR: reporting odds ratio; SOC: System Organ Class.

General disorders and administration site conditions

3,047

1.1 (1.06–1.15)

1.08 (24.49)

1.08 (1.04)

0.12 (0.06)

Nervous system disorders

2,909

2.9 (2.78–3.02)

2.55 (2,947.53)

2.55 (2.45)

1.35 (1.29)

Gastrointestinal disorders

1,847

1.54 (1.47–1.62)

1.48 (311.11)

1.48 (1.41)

0.56 (0.49)

Investigations

1,084

1.19 (1.12–1.27)

1.18 (30.95)

1.18 (1.11)

0.24 (0.15)

Musculoskeletal and connective tissue disorders

1,045

1.32 (1.24–1.4)

1.3 (74.89)

1.3 (1.22)

Injury, poisoning, and procedural complications

1,009

0.47 (0.44–0.5)

0.5 (577.24)

0.5 (0.47)

−1 (−1.09)

Infections and infestations

908

1 (0.94–1.07)

1 (0.01)

1 (0.94)

0.01 (−0.09)

Psychiatric disorders

679

0.8 (0.74–0.86)

0.81 (33.06)

0.81 (0.75)

−0.31 (−0.42)

Respiratory, thoracic, and mediastinal disorders

515

0.71 (0.65–0.77)

0.72 (61)

0.72 (0.66)

−0.48 (−0.61)

Skin and subcutaneous tissue disorders

495

0.55 (0.5–0.6)

0.56 (175.44)

0.57 (0.52)

−0.82 (−0.95)

Eye disorders

442

1.43 (1.3–1.57)

1.42 (55.76)

1.42 (1.29)

0.5 (0.36)

Vascular disorders

363

1.25 (1.13–1.39)

1.24 (17.8)

1.24 (1.12)

0.32 (0.16)

Cardiac disorders

242

0.78 (0.69–0.89)

0.79 (14.5)

0.79 (0.69)

−0.35 (−0.53)

Renal and urinary disorders

202

0.71 (0.62–0.81)

0.71 (24.26)

0.71 (0.62)

−0.49 (−0.69)

Blood and lymphatic system disorders

178

0.66 (0.57–0.76)

0.66 (31.88)

0.66 (0.57)

−0.6 (−0.82)

Neoplasms benign, malignant, and unspecified (cysts and polyps)

177

0.29 (0.25–0.33)

0.3 (306.53)

0.3 (0.26)

−1.75 (−1.96)

Metabolism and nutrition disorders

160

0.52 (0.44–0.61)

0.52 (70.41)

0.52 (0.45)

−0.93 (−1.16)

Immune system disorders

119

0.65 (0.54–0.78)

0.65 (22.71)

0.65 (0.54)

−0.62 (−0.88)

Surgical and medical procedures

110

0.45 (0.38–0.55)

0.46 (72.23)

0.46 (0.38)

−1.13 (−1.4)

Reproductive system and breast disorders

0.74 (0.59–0.94)

0.74 (6.35)

0.74 (0.59)

−0.43 (−0.76)

Ear and labyrinth disorders

1.02 (0.8–1.3)

1.02 (0.04)

1.02 (0.8)

0.03 (−0.32)

Pregnancy, puerperium, and perinatal conditions

1.19 (0.93–1.53)

1.19 (1.99)

1.19 (0.93)

0.26 (−0.11)

Social circumstances

0.77 (0.6–1)

0.77 (4)

0.77 (0.6)

−0.37 (−0.74)

Hepatobiliary disorders

0.39 (0.29–0.51)

0.39 (50.64)

0.39 (0.3)

−1.37 (−1.75)

Product issues

0.09 (0.06–0.13)

0.09 (259.85)

0.09 (0.06)

−3.46 (−3.95)

Endocrine disorders

0.32 (0.19–0.55)

0.32 (19.8)

0.32 (0.19)

−1.63 (−2.3)

Congenital, familial, and genetic disorders

0.11 (0.04–0.28)

0.11 (30.43)

0.11 (0.04)

−3.24 (−4.25)

↓ **Table 5.** Top PT-Level AE Reports Involving Ozanimod Ranked by Report Frequency
SOC	PTs	Case reports	ROR (95% CI)	PRR (χ²)	EBGM (EBGM05)	IC (IC025)
A positive signal was defined as meeting the predefined criteria of report count ≥ 3, lower limit of ROR 95% CI > 1, lower limit of PRR 95% CI > 1, EBGM05 > 2, and IC025 > 0. AE: adverse event; CI: confidence interval; EBGM: empirical Bayesian geometric mean; IC: information component; PRR: proportional reporting ratio; PT: Preferred Term; ROR: reporting odds ratio; SOC: System Organ Class.
General disorders and administration site conditions	Fatigue	660	3.38 (3.13–3.65)	3.28 (1,057.57)	3.28 (3.03)	1.71 (1.59)
Nervous system disorders	Multiple sclerosis relapse	548	42 (38.53–45.79)	40.59 (20,611.49)	39.53 (36.26)	5.3 (5.08)
Nervous system disorders	Headache	475	3.42 (3.12–3.74)	3.34 (786.01)	3.34 (3.05)	1.74 (1.6)
Nervous system disorders	Dizziness	314	2.95 (2.64–3.3)	2.91 (395.93)	2.91 (2.6)	1.54 (1.37)
Gastrointestinal disorders	Colitis ulcerative	214	14.07 (12.29–16.12)	13.9 (2,539.94)	13.78 (12.03)	3.78 (3.5)
Musculoskeletal and connective tissue disorders	Back pain	201	3.81 (3.32–4.38)	3.78 (410.94)	3.77 (3.28)	1.91 (1.69)
General disorders and administration site conditions	Adverse event	169	9.02 (7.75–10.5)	8.93 (1,184.66)	8.88 (7.63)	3.15 (2.86)
Nervous system disorders	Multiple sclerosis	155	13.27 (11.32–15.55)	13.15 (1,725.96)	13.04 (11.13)	3.71 (3.36)
Nervous system disorders	Hypoesthesia	143	4.37 (3.71–5.16)	4.34 (367.82)	4.33 (3.68)	2.12 (1.84)
Vascular disorders	Hypertension	125	2.45 (2.06–2.93)	2.44 (106.59)	2.44 (2.05)	1.29 (1.01)
Psychiatric disorders	Depression	117	2.65 (2.21–3.18)	2.64 (119.54)	2.64 (2.2)	1.4 (1.11)
Infections and infestations	Urinary tract infection	110	2.53 (2.09–3.05)	2.51 (100.45)	2.51 (2.08)	1.33 (1.03)
General disorders and administration site conditions	Gait disturbance	109	2.49 (2.06–3)	2.48 (96.03)	2.47 (2.05)	1.31 (1.01)
Nervous system disorders	Paresthesia	104	3.12 (2.57–3.78)	3.11 (148.5)	3.1 (2.56)	1.63 (1.32)
Investigations	Increased blood pressure	102	2.6 (2.14–3.16)	2.59 (99.77)	2.59 (2.13)	1.37 (1.06)
Nervous system disorders	Balance disorder	100	5.31 (4.36–6.47)	5.29 (346.68)	5.27 (4.33)	2.4 (2.05)
Investigations	Decreased lymphocyte count	99	18.74 (15.36–22.87)	18.63 (1,631.97)	18.41 (15.09)	4.2 (3.68)
Musculoskeletal and connective tissue disorders	Muscle spasms	98	2.57 (2.1–3.13)	2.56 (92.98)	2.55 (2.09)	1.35 (1.04)
Investigations	Decreased white blood cell count	96	3.23 (2.64–3.95)	3.22 (146.73)	3.21 (2.63)	1.68 (1.36)
Nervous system disorders	Memory impairment	95	2.83 (2.31–3.47)	2.82 (111.75)	2.82 (2.3)	1.49 (1.17)
Eye disorders	Visual impairment	93	2.8 (2.28–3.43)	2.79 (106.8)	2.79 (2.27)	1.48 (1.15)
Nervous system disorders	Migraine	89	3.59 (2.92–4.42)	3.58 (165.11)	3.57 (2.9)	1.84 (1.49)
Eye disorders	Vision blurred	88	3 (2.43–3.7)	2.99 (116.31)	2.98 (2.42)	1.58 (1.24)
Injury, poisoning, and procedural complications	Maternal exposure during pregnancy	86	2.85 (2.31–3.53)	2.84 (102.85)	2.84 (2.3)	1.51 (1.17)
Investigations	Decreased heart rate	80	7.7 (6.17–9.59)	7.66 (461.3)	7.63 (6.12)	2.93 (2.5)
Blood and lymphatic system disorders	Lymphopenia	78	19.57 (15.64–24.48)	19.47 (1,349.54)	19.23 (15.37)	4.27 (3.64)
Vascular disorders	Hemorrhage	78	3.28 (2.62–4.09)	3.27 (122.5)	3.26 (2.61)	1.71 (1.34)
Cardiac disorders	Palpitations	77	3.12 (2.49–3.9)	3.11 (110.05)	3.1 (2.48)	1.63 (1.27)
Psychiatric disorders	Stress	76	3.92 (3.13–4.91)	3.9 (163.88)	3.9 (3.11)	1.96 (1.58)
Gastrointestinal disorders	Hematochezia	70	4.4 (3.47–5.56)	4.38 (182.26)	4.37 (3.45)	2.13 (1.72)

↓ Table 5. Top PT-Level AE Reports Involving Ozanimod Ranked by Report Frequency

SOC

PTs

Case reports

ROR (95% CI)

PRR (χ²)

EBGM (EBGM05)

IC (IC025)

General disorders and administration site conditions

Fatigue

660

3.38 (3.13–3.65)

3.28 (1,057.57)

3.28 (3.03)

1.71 (1.59)

Nervous system disorders

Multiple sclerosis relapse

548

42 (38.53–45.79)

40.59 (20,611.49)

39.53 (36.26)

5.3 (5.08)

Nervous system disorders

Headache

475

3.42 (3.12–3.74)

3.34 (786.01)

3.34 (3.05)

1.74 (1.6)

Nervous system disorders

Dizziness

314

2.95 (2.64–3.3)

2.91 (395.93)

2.91 (2.6)

1.54 (1.37)

Gastrointestinal disorders

Colitis ulcerative

214

14.07 (12.29–16.12)

13.9 (2,539.94)

13.78 (12.03)

3.78 (3.5)

Musculoskeletal and connective tissue disorders

Back pain

201

3.81 (3.32–4.38)

3.78 (410.94)

3.77 (3.28)

1.91 (1.69)

General disorders and administration site conditions

Adverse event

169

9.02 (7.75–10.5)

8.93 (1,184.66)

8.88 (7.63)

3.15 (2.86)

Nervous system disorders

Multiple sclerosis

155

13.27 (11.32–15.55)

13.15 (1,725.96)

13.04 (11.13)

3.71 (3.36)

Nervous system disorders

Hypoesthesia

143

4.37 (3.71–5.16)

4.34 (367.82)

4.33 (3.68)

2.12 (1.84)

Vascular disorders

Hypertension

125

2.45 (2.06–2.93)

2.44 (106.59)

2.44 (2.05)

1.29 (1.01)

Psychiatric disorders

Depression

117

2.65 (2.21–3.18)

2.64 (119.54)

2.64 (2.2)

1.4 (1.11)

Infections and infestations

Urinary tract infection

110

2.53 (2.09–3.05)

2.51 (100.45)

2.51 (2.08)

1.33 (1.03)

General disorders and administration site conditions

Gait disturbance

109

2.49 (2.06–3)

2.48 (96.03)

2.47 (2.05)

1.31 (1.01)

Nervous system disorders

Paresthesia

104

3.12 (2.57–3.78)

3.11 (148.5)

3.1 (2.56)

1.63 (1.32)

Investigations

Increased blood pressure

102

2.6 (2.14–3.16)

2.59 (99.77)

2.59 (2.13)

1.37 (1.06)

Nervous system disorders

Balance disorder

100

5.31 (4.36–6.47)

5.29 (346.68)

5.27 (4.33)

2.4 (2.05)

Investigations

Decreased lymphocyte count

18.74 (15.36–22.87)

18.63 (1,631.97)

18.41 (15.09)

4.2 (3.68)

Musculoskeletal and connective tissue disorders

Muscle spasms

2.57 (2.1–3.13)

2.56 (92.98)

2.55 (2.09)

1.35 (1.04)

Investigations

Decreased white blood cell count

3.23 (2.64–3.95)

3.22 (146.73)

3.21 (2.63)

1.68 (1.36)

Nervous system disorders

Memory impairment

2.83 (2.31–3.47)

2.82 (111.75)

2.82 (2.3)

1.49 (1.17)

Eye disorders

Visual impairment

2.8 (2.28–3.43)

2.79 (106.8)

2.79 (2.27)

1.48 (1.15)

Nervous system disorders

Migraine

3.59 (2.92–4.42)

3.58 (165.11)

3.57 (2.9)

1.84 (1.49)

Eye disorders

Vision blurred

3 (2.43–3.7)

2.99 (116.31)

2.98 (2.42)

1.58 (1.24)

Injury, poisoning, and procedural complications

Maternal exposure during pregnancy

2.85 (2.31–3.53)

2.84 (102.85)

2.84 (2.3)

1.51 (1.17)

Investigations

Decreased heart rate

7.7 (6.17–9.59)

7.66 (461.3)

7.63 (6.12)

2.93 (2.5)

Blood and lymphatic system disorders

Lymphopenia

19.57 (15.64–24.48)

19.47 (1,349.54)

19.23 (15.37)

4.27 (3.64)

Vascular disorders

Hemorrhage

3.28 (2.62–4.09)

3.27 (122.5)

3.26 (2.61)

1.71 (1.34)

Cardiac disorders

Palpitations

3.12 (2.49–3.9)

3.11 (110.05)

3.1 (2.48)

1.63 (1.27)

Psychiatric disorders

Stress

3.92 (3.13–4.91)

3.9 (163.88)

3.9 (3.11)

1.96 (1.58)

Gastrointestinal disorders

Hematochezia

4.4 (3.47–5.56)

4.38 (182.26)

4.37 (3.45)

2.13 (1.72)

↓ **Table 6.** Top PT-Level Disproportionality Signals Involving Ozanimod Ranked by EBGM
SOC	PTs	Case reports	ROR (95% CI)	PRR (χ²)	EBGM (EBGM05)	IC (IC025)
A positive signal was defined as meeting the predefined criteria of report count ≥ 3, lower limit of ROR 95% CI > 1, lower limit of PRR 95% CI > 1, EBGM05 > 2, and IC025 > 0. AE: adverse event; CI: confidence interval; EBGM: empirical Bayesian geometric mean; IC: information component; PRR: proportional reporting ratio; PT: Preferred Term; ROR: reporting odds ratio; SOC: System Organ Class.
Nervous system disorders	Multiple sclerosis relapse	548	42 (38.53–45.79)	40.59 (20,611.49)	39.53 (36.26)	5.3 (5.08)
Nervous system disorders	Progressive multiple sclerosis	8	40.36 (19.99–81.47)	40.34 (298.73)	39.29 (19.46)	5.3 (1.93)
Gastrointestinal disorders	Proctitis ulcerative	4	32.12 (11.93–86.51)	32.11 (118.02)	31.45 (11.68)	4.98 (0.84)
Investigations	Lymphocyte count abnormal	9	26.14 (13.52–50.53)	26.12 (213.66)	25.68 (13.28)	4.68 (1.97)
Investigations	Decreased T-lymphocyte count	5	26.02 (10.74–63)	26.01 (118.16)	25.58 (10.56)	4.68 (1.14)
Reproductive system and breast disorders	Uterine disorder	9	23.59 (12.21–45.58)	23.57 (191.49)	23.22 (12.02)	4.54 (1.93)
Investigations	Head magnetic resonance imaging abnormal	10	22.26 (11.92–41.58)	22.25 (199.93)	21.93 (11.74)	4.46 (2.04)
Eye disorders	Macular edema	23	19.96 (13.22–30.12)	19.93 (408.03)	19.68 (13.04)	4.3 (2.87)
Blood and lymphatic system disorders	Lymphopenia	78	19.57 (15.64–24.48)	19.47 (1,349.54)	19.23 (15.37)	4.27 (3.64)
Injury, poisoning, and procedural complications	Traumatic fracture	4	18.65 (6.95–49.99)	18.64 (65.95)	18.42 (6.87)	4.2 (0.74)
Investigations	Decreased lymphocyte count	99	18.74 (15.36–22.87)	18.63 (1,631.97)	18.41 (15.09)	4.2 (3.68)
Infections and infestations	Gastroenteritis Escherichia coli	3	17.95 (5.75–56.03)	17.94 (47.42)	17.74 (5.68)	4.15 (0.32)
Gastrointestinal disorders	Colitis ulcerative	214	14.07 (12.29–16.12)	13.9 (2,539.94)	13.78 (12.03)	3.78 (3.5)
Nervous system disorders	Multiple sclerosis	155	13.27 (11.32–15.55)	13.15 (1,725.96)	13.04 (11.13)	3.71 (3.36)
Reproductive system and breast disorders	Penile swelling	3	11.73 (3.76–36.53)	11.72 (29.2)	11.64 (3.74)	3.54 (0.22)
Nervous system disorders	Optic neuritis	20	11.46 (7.38–17.79)	11.44 (189.16)	11.36 (7.32)	3.51 (2.29)
Nervous system disorders	Head titubation	3	10.41 (3.34–32.39)	10.4 (25.32)	10.34 (3.32)	3.37 (0.18)
Investigations	Decreased CD4 lymphocytes	5	10.35 (4.29–24.94)	10.35 (41.92)	10.28 (4.27)	3.36 (0.83)
Nervous system disorders	Peroneal nerve palsy	11	9.67 (5.35–17.5)	9.67 (84.92)	9.61 (5.31)	3.26 (1.65)
Nervous system disorders	Central nervous system lesion	22	9.01 (5.92–13.7)	9 (155.48)	8.95 (5.88)	3.16 (2.13)
Cardiac disorders	Cardiac flutter	13	8.97 (5.2–15.48)	8.97 (91.46)	8.92 (5.17)	3.16 (1.74)
General disorders and administration site conditions	Adverse event	169	9.02 (7.75–10.5)	8.93 (1,184.66)	8.88 (7.63)	3.15 (2.86)
Renal and urinary disorders	Bladder disorder	20	8.78 (5.66–13.63)	8.77 (136.89)	8.72 (5.62)	3.12 (2.04)
Nervous system disorders	Trigeminal neuralgia	8	8.75 (4.37–17.54)	8.75 (54.58)	8.7 (4.34)	3.12 (1.26)
Eye disorders	Retinal edema	4	8.57 (3.21–22.89)	8.56 (26.57)	8.52 (3.19)	3.09 (0.47)
Ear and labyrinth disorders	Auditory disorder	4	8.12 (3.04–21.69)	8.12 (24.82)	8.08 (3.02)	3.01 (0.45)
Psychiatric disorders	Feeling of despair	9	8.06 (4.19–15.52)	8.06 (55.34)	8.02 (4.16)	3 (1.32)
Neoplasms benign, malignant, and unspecified (cysts and polyps)	Papillary thyroid cancer	3	7.78 (2.5–24.19)	7.78 (17.62)	7.74 (2.49)	2.95 (0.08)
Psychiatric disorders	Decreased interest	8	7.78 (3.88–15.6)	7.78 (47.03)	7.74 (3.87)	2.95 (1.18)
Investigations	Decreased heart rate	80	7.7 (6.17–9.59)	7.66 (461.3)	7.63 (6.12)	2.93 (2.5)

↓ Table 6. Top PT-Level Disproportionality Signals Involving Ozanimod Ranked by EBGM

SOC

PTs

Case reports

ROR (95% CI)

PRR (χ²)

EBGM (EBGM05)

IC (IC025)

Nervous system disorders

Multiple sclerosis relapse

548

42 (38.53–45.79)

40.59 (20,611.49)

39.53 (36.26)

5.3 (5.08)

Nervous system disorders

Progressive multiple sclerosis

40.36 (19.99–81.47)

40.34 (298.73)

39.29 (19.46)

5.3 (1.93)

Gastrointestinal disorders

Proctitis ulcerative

32.12 (11.93–86.51)

32.11 (118.02)

31.45 (11.68)

4.98 (0.84)

Investigations

Lymphocyte count abnormal

26.14 (13.52–50.53)

26.12 (213.66)

25.68 (13.28)

4.68 (1.97)

Investigations

Decreased T-lymphocyte count

26.02 (10.74–63)

26.01 (118.16)

25.58 (10.56)

4.68 (1.14)

Reproductive system and breast disorders

Uterine disorder

23.59 (12.21–45.58)

23.57 (191.49)

23.22 (12.02)

4.54 (1.93)

Investigations

Head magnetic resonance imaging abnormal

22.26 (11.92–41.58)

22.25 (199.93)

21.93 (11.74)

4.46 (2.04)

Eye disorders

Macular edema

19.96 (13.22–30.12)

19.93 (408.03)

19.68 (13.04)

4.3 (2.87)

Blood and lymphatic system disorders

Lymphopenia

19.57 (15.64–24.48)

19.47 (1,349.54)

19.23 (15.37)

4.27 (3.64)

Injury, poisoning, and procedural complications

Traumatic fracture

18.65 (6.95–49.99)

18.64 (65.95)

18.42 (6.87)

4.2 (0.74)

Investigations

Decreased lymphocyte count

18.74 (15.36–22.87)

18.63 (1,631.97)

18.41 (15.09)

4.2 (3.68)

Infections and infestations

Gastroenteritis Escherichia coli

17.95 (5.75–56.03)

17.94 (47.42)

17.74 (5.68)

4.15 (0.32)

Gastrointestinal disorders

Colitis ulcerative

214

14.07 (12.29–16.12)

13.9 (2,539.94)

13.78 (12.03)

3.78 (3.5)

Nervous system disorders

Multiple sclerosis

155

13.27 (11.32–15.55)

13.15 (1,725.96)

13.04 (11.13)

3.71 (3.36)

Reproductive system and breast disorders

Penile swelling

11.73 (3.76–36.53)

11.72 (29.2)

11.64 (3.74)

3.54 (0.22)

Nervous system disorders

Optic neuritis

11.46 (7.38–17.79)

11.44 (189.16)

11.36 (7.32)

3.51 (2.29)

Nervous system disorders

Head titubation

10.41 (3.34–32.39)

10.4 (25.32)

10.34 (3.32)

3.37 (0.18)

Investigations

Decreased CD4 lymphocytes

10.35 (4.29–24.94)

10.35 (41.92)

10.28 (4.27)

3.36 (0.83)

Nervous system disorders

Peroneal nerve palsy

9.67 (5.35–17.5)

9.67 (84.92)

9.61 (5.31)

3.26 (1.65)

Nervous system disorders

Central nervous system lesion

9.01 (5.92–13.7)

9 (155.48)

8.95 (5.88)

3.16 (2.13)

Cardiac disorders

Cardiac flutter

8.97 (5.2–15.48)

8.97 (91.46)

8.92 (5.17)

3.16 (1.74)

General disorders and administration site conditions

Adverse event

169

9.02 (7.75–10.5)

8.93 (1,184.66)

8.88 (7.63)

3.15 (2.86)

Renal and urinary disorders

Bladder disorder

8.78 (5.66–13.63)

8.77 (136.89)

8.72 (5.62)

3.12 (2.04)

Nervous system disorders

Trigeminal neuralgia

8.75 (4.37–17.54)

8.75 (54.58)

8.7 (4.34)

3.12 (1.26)

Eye disorders

Retinal edema

8.57 (3.21–22.89)

8.56 (26.57)

8.52 (3.19)

3.09 (0.47)

Ear and labyrinth disorders

Auditory disorder

8.12 (3.04–21.69)

8.12 (24.82)

8.08 (3.02)

3.01 (0.45)

Psychiatric disorders

Feeling of despair

8.06 (4.19–15.52)

8.06 (55.34)

8.02 (4.16)

3 (1.32)

Neoplasms benign, malignant, and unspecified (cysts and polyps)

Papillary thyroid cancer

7.78 (2.5–24.19)

7.78 (17.62)

7.74 (2.49)

2.95 (0.08)

Psychiatric disorders

Decreased interest

7.78 (3.88–15.6)

7.78 (47.03)

7.74 (3.87)

2.95 (1.18)

Investigations

Decreased heart rate

7.7 (6.17–9.59)

7.66 (461.3)

7.63 (6.12)

2.93 (2.5)

↓ **Table 7.** Indication-Stratified Counts of Reviewer-Prioritized Events
AEs	UC (no. of events, no. of reports)	MS (no. of events, no. of reports)	Interpretation
AE: adverse event; MS: multiple sclerosis; UC: ulcerative colitis.
Optic neuritis	0 (0)	19 (19)	Observed only in MS stratum
Gastroenteritis	0 (0)	0 (0)	No cases in both strata
Any fracture	8 (9)	21 (27)	More frequent in MS stratum
Any bladder disorder	3 (3)	27 (27)	Observed in both strata
Traumatic fracture	0 (0)	4 (4)	Observed only in MS stratum

↓ Table 7. Indication-Stratified Counts of Reviewer-Prioritized Events

AEs

UC (no. of events, no. of reports)

MS (no. of events, no. of reports)

Interpretation

AE: adverse event; MS: multiple sclerosis; UC: ulcerative colitis.

Optic neuritis

0 (0)

19 (19)

Observed only in MS stratum

Gastroenteritis

0 (0)

No cases in both strata

Any fracture

8 (9)

21 (27)

More frequent in MS stratum

Any bladder disorder

3 (3)

27 (27)

Observed in both strata

Traumatic fracture

0 (0)

4 (4)

Observed only in MS stratum