Extending the evidence on ustekinumab safety in Crohn’s disease: A pharmacovigilance disproportionality analysis of FAERS data

Table 1 Basic characteristics of Crohn’s disease patients with adverse events associated with ustekinumab from the United States Food and Drug Administration Adverse Event Reporting System database, n (%)

Characteristics	Total
Number of events	21441 (100)
Gender
Female	12173 (56.8)
Male	7460 (34.8)
Not specified	1808 (8.4)
Age (year)
< 18	550 (2.6)
18-64.9	10959 (51.1)
65-85	1970 (9.2)
> 85	69 (0.3)
Missing	7893 (36.8)
Reporter
Consumer	8912 (41.6)
Health professional	5656 (26.4)
Pharmacist	1780 (8.3)
Physician	3289 (15.3)
Missing	1804 (8.4)
Reported countries (top 3)
United States	11897 (55.5)
Canada	4551 (21.2)
United Kingdom	1721 (8.0)
Other	3272 (15.26)
Outcome
Death	303 (1.4)
Hospitalization	4770 (22.2)
Life-threatening	249 (1.2)
Other	16119 (75.2)
Reporting year
2016	61 (0.3)
2017	962 (4.5)
2018	2151 (10.0)
2019	2589 (12.1)
2020	5164 (24.1)
2021	2412 (11.2)
2022	2505 (11.7)
2023	2351 (11.0)
2024	1712 (8.0)
2025	1534 (7.2)

Table 2 Top 40 preferred terms associated with ustekinumab in Crohn’s disease, ranked by reporting frequency

PT	Case	ROR (95%CI)	PRR (χ2)
Lower respiratory tract infection	909	7.26 (6.7-7.87)	7.2 (3177.4)
Infusion related reaction	698	2.49 (2.3-2.7)	2.48 (524.16)
Clostridium difficile infection	484	3 (2.71-3.31)	2.99 (524.89)
Abscess	481	2.01 (1.82-2.21)	2 (211.21)
Anal abscess	331	2.26 (2.02-2.54)	2.26 (199.72)
Cellulitis	247	2.97 (2.59-3.41)	2.97 (264.89)
Kidney infection	191	3.96 (3.37-4.65)	3.95 (326.71)
Tooth abscess	151	4.69 (3.9-5.64)	4.68 (325.29)
Abdominal abscess	149	2.22 (1.86-2.64)	2.21 (85.35)
Upper respiratory tract infection	140	2.08 (1.74-2.49)	2.08 (68.16)
Respiratory tract infection	137	4.69 (3.86-5.7)	4.69 (295.49)
Cholelithiasis	131	2.02 (1.68-2.43)	2.02 (58.54)
Postoperative wound infection	120	2.33 (1.92-2.82)	2.32 (77.4)
Anaphylactic reaction	115	2.14 (1.76-2.61)	2.14 (60.55)
Rectal abscess	113	2.35 (1.93-2.87)	2.35 (74.76)
Breast cancer	86	2.27 (1.81-2.86)	2.27 (52.51)
Gastroenteritis	80	2.13 (1.68-2.7)	2.13 (41.49)
Infected fistula	65	3 (2.3-3.93)	3 (71.12)
Tonsillitis	65	2.66 (2.04-3.47)	2.66 (56.28)
Squamous cell carcinoma	64	2.19 (1.68-2.85)	2.19 (35.62)
Subcutaneous abscess	64	2.16 (1.66-2.82)	2.16 (34.5)
Device related infection	55	2.39 (1.79-3.18)	2.39 (37.69)
Transient ischaemic attack	54	2.17 (1.63-2.89)	2.17 (29.37)
Abscess limb	50	2.1 (1.56-2.83)	2.1 (25.03)
Multiple sclerosis	44	2.13 (1.55-2.92)	2.13 (22.71)
Peritonitis	44	2.08 (1.52-2.86)	2.08 (21.46)
Facial paralysis	43	4 (2.85-5.62)	4 (74.74)
Liver function test abnormal	43	3.42 (2.45-4.77)	3.42 (58.69)
Escherichia infection	39	2.37 (1.68-3.32)	2.36 (26.16)
Gastroenteritis norovirus	38	10.98 (7.16-16.85)	10.98 (190.62)
Posterior reversible encephalopathy syndrome	38	10.33 (6.77-15.74)	10.32 (181.77)
Complication associated with device	36	3.11 (2.17-4.47)	3.11 (42.04)
Pyelonephritis	33	2.03 (1.41-2.92)	2.03 (14.96)
Gastric infection	33	2.03 (1.41-2.92)	2.03 (14.96)
Mastitis	32	4.35 (2.92-6.47)	4.35 (62.45)
Abdominal infection	30	2.83 (1.91-4.19)	2.83 (29.37)
Interstitial lung disease	30	2.24 (1.52-3.29)	2.24 (17.65)
Groin abscess	29	3.13 (2.09-4.68)	3.13 (34.08)
Infected cyst	28	3.34 (2.21-5.04)	3.34 (36.77)
Cholecystitis	28	2.38 (1.59-3.55)	2.38 (19)

PT: Preferred term; ROR: Reporting odds ratio; PRR: Proportional reporting ratio.

Table 3 Top 40 preferred terms associated with ustekinumab in Crohn’s disease, ranked by signal strength

PT	Case	ROR (95%Cl)	PRR (χ2)
Cavernous sinus thrombosis	7	95.07 (11.7-772.77)	95.07 (81.44)
Rubella	3	40.74 (4.24-391.71)	40.74 (29.08)
Mastocytosis	3	40.74 (4.24-391.71)	40.74 (29.08)
Vagus nerve disorder	3	40.74 (4.24-391.71)	40.74 (29.08)
Application site vesicles	6	27.16 (6.79-108.62)	27.16 (50.4)
Pneumocephalus	4	27.16 (4.97-148.3)	27.16 (33.6)
Enzyme abnormality	4	27.16 (4.97-148.3)	27.16 (33.6)
Eating disorder symptom	9	24.45 (8.19-72.95)	24.45 (72.28)
External ear cellulitis	10	22.64 (8.23-62.29)	22.63 (77.55)
Neuroendocrine carcinoma metastatic	5	22.64 (5.41-94.72)	22.63 (38.77)
Ophthalmic vein thrombosis	5	22.64 (5.41-94.72)	22.63 (38.77)
Dermatitis exfoliative	9	20.37 (7.25-57.24)	20.37 (66.31)
Neonatal seizure	3	20.37 (3.4-121.92)	20.37 (22.1)
Autoscopy	3	20.37 (3.4-121.92)	20.37 (22.1)
Hyperprolactinaemia	3	20.37 (3.4-121.92)	20.37 (22.1)
Chorioretinopathy	4	18.11 (4.05-80.91)	18.11 (27.71)
Pulseless electrical activity	6	16.3 (4.97-53.4)	16.3 (39.16)
Polymyositis	4	13.58 (3.4-54.31)	13.58 (23.31)
Klebsiella sepsis	4	13.58 (3.4-54.31)	13.58 (23.31)
Periumbilical abscess	4	13.58 (3.4-54.31)	13.58 (23.31)
Vascular access site infection	4	13.58 (3.4-54.31)	13.58 (23.31)
Cryptorchism	3	13.58 (2.74-67.29)	13.58 (17.48)
Fallot’s tetralogy	3	13.58 (2.74-67.29)	13.58 (17.48)
Eczema herpeticum	3	13.58 (2.74-67.29)	13.58 (17.48)
Trigeminal nerve disorder	3	13.58 (2.74-67.29)	13.58 (17.48)
Arteriovenous malformation	3	13.58 (2.74-67.29)	13.58 (17.48)
Gastroenteritis norovirus	38	10.98 (7.16-16.85)	10.98 (190.62)
Muscle abscess	7	10.56 (3.93-28.37)	10.56 (34.09)
Posterior reversible encephalopathy syndrome	38	10.33 (6.77-15.74)	10.32 (181.77)
Language disorder	6	10.19 (3.53-29.36)	10.19 (28.4)
Mumps	3	10.19 (2.28-45.51)	10.19 (14.2)
Human chorionic gonadotropin increased	3	10.19 (2.28-45.51)	10.19 (14.2)
Blood zinc decreased	5	9.7 (3.08-30.57)	9.7 (22.76)
Pharyngotonsillitis	7	9.51 (3.62-24.98)	9.51 (31.34)
Haemophilus infection	4	9.05 (2.55-32.09)	9.05 (17.19)
Ventricular septal defect	5	8.49 (2.78-25.95)	8.49 (20.33)
Chlamydial infection	16	8.36 (4.48-15.58)	8.36 (64.16)
Gastritis bacterial	8	8.36 (3.46-20.17)	8.36 (32.08)
Staring	3	8.15 (1.95-34.1)	8.15 (11.76)
Ewing’s sarcoma	3	8.15 (1.95-34.1)	8.15 (11.76)

PT: Preferred term; ROR: Reporting odds ratio; PRR: Proportional reporting ratio.