A0389 - Risk of Tofacitinib-Related Adverse Events in Patients With Ulcerative Colitis: A Nationwide Propensity-Matched Cohort Study

Sunday, October 23, 2022

5:00 PM – 7:00 PM ET

Location: Crown Ballroom

Has Audio

Presenting Author(s)

GK

Gursimran S. Kochhar, MD

Allegheny Health Network
Pittsburgh, PA

Gursimran S. Kochhar, MD¹, Aakash Desai, MD², Raymond Cross, MD³, Francis A. Farraye, MD, MSc⁴, Stephen B. Hanauer, MD⁵, Parambir S. Dulai, MD⁵
¹Allegheny Health Network, Pittsburgh, PA; ²MetroHealth Medical Center/Case Western Reserve University, Cleveland, OH; ³University of Maryland Medical Center, Baltimore, MD; ⁴Mayo Clinic, Jacksonville, FL; ⁵Northwestern University, Chicago, IL

Introduction: A recent randomized, open-label, safety end-point trial found an increased risk of major adverse cardiovascular events (MACE) and malignancy in patients with rheumatoid arthritis who received tofacitinib compared to tumor necrosis factor inhibitor (TNFi). The risk of adverse events in patients with ulcerative colitis (UC) on tofacitinib from population-based observational studies is limited

Methods: A retrospective cohort study was conducted using TriNetX, a multi-institutional database of more than 70 million patients from 49 healthcare organizations in the USA. We compared the 1-, 2- and 3-year risk of MACE, malignancy, opportunistic infections (OIs) and venous thromboembolism (VTE) between patients with UC on tofacitinib and other biologic agents (control cohort). Sub-group analysis was performed based on type of biologic agent which included TNFi, vedolizumab, and ustekinumab. Exclusion criteria included patients who were on the biologic agent for less than 3 months or had a prior history of any adverse event. 1:1 propensity-score matching was performed for age, gender, race, ethnicity, other autoimmune diseases, primary thrombophilia and all known risk factors for MACE between all the cohorts. Adjusted odds ratios (aOR) with 95% confidence interval (CI) were calculated to express the risk of each adverse event

Results: Of a total of 94,321 patients with UC, 1056 patients received tofacitinib (mean age 47 +/- 16, 53% male), 4,285 received an TNFi, 2,402 patients received vedolizumab (VDZ), and 1,335 received ustekinumab. There was no difference in the 1-, 2-, and 3-year risk of MACE, malignancy, OIs, and VTE between patients on tofacitinib compared to other biologic agents . In sub-group analysis, there was no difference in the 1-, 2- and 3-year risk of MACE, malignancy and VTE between patients on tofacitinib compared individually to TNFi, vedolizumab and ustekinumab (Table 1). There is an increased 1-year risk of OIs in patients on tofacitinib compared to TNFi and vedolizumab, and an increased 1-, 2- and 3-year risk of OIs compared to ustekinumab

Discussion: In our propensity-matched cohort study of patients with UC, tofacitinib does not confer a higher risk of MACE, malignancy, and VTE than other biologic agents. Further studies are needed to understand the dose-related effect of tofacitinib on the risk of these adverse events

Drug class	Outcome	Year	aOR	95% CI
TNFi
	MACE	1	0.87	0.46-1.62
		2	0.98	0.56-1.69
		3	1.22	0.63-2.37
	Malignancy
		1	0.93	0.50-1.76
		2	1.08	0.61-1.89
		3	1.61	0.71-3.64
	OI
		1	1.55	1.01-2.37
		2	1.32	0.91-1.93
		3	1.24	0.79-1.94
	VTE
		1	1.18	0.63-2.20
		2	1.06	0.61-1.84
		3	1.56	0.78-3.13
Vedolizumab
	MACE
		1	0.83	0.45-1.55
		2	0.97	0.55-1.70
		3	0.96	0.51-1.82
	Malignancy
		1	1.17	0.60-2.30
		2	1.18	0.66-2.10
		3	0.89	0.42-1.88
	OI
		1	1.82	1.15-2.87
		2	1.33	0.90-1.96
		3	1.42	0.86-2.32
	VTE
		1	1.58	0.76-3.28
		2	1.3	0.71-2.35
		3	2.1	0.97-4.52
Ustekinumab
	MACE	1	1.63	0.73-3.62
		2	2.06	0.99-4.30
		3	1.78	0.80-3.99
	Malignancy
		1	1.03	0.53-1.99
		2	1.32	0.68-2.57
		3	0.82	0.38-1.74
	OI
		1	1.91	1.14-3.20
		2	2.33	1.36-4.01
		3	2.23	1.12-4.44
	VTE
		1	1.97	0.91-4.24
		2	1.85	0.85-4.02
		3	1.55	0.69-3.350

Table: Risk of adverse events between patients on tofacitinib compared to TNFi, vedolizumab and ustekinumab
*aOR: adjusted odds ratio

Disclosures:

Gursimran Kochhar: GIE Medical – Advisor or Review Panel Member. Lilly Pharma – Advisor or Review Panel Member.

Aakash Desai indicated no relevant financial relationships.

Raymond Cross: Abbvie – Advisory Committee/Board Member, Consultant. BMS – Advisory Committee/Board Member. Fzata – Consultant. Janssen – Advisory Committee/Board Member, Grant/Research Support. Magellan Health – Consultant. Pfizer – Advisory Committee/Board Member, Consultant. Samsung bioepis – Consultant. Takeda – Advisory Committee/Board Member.

Francis Farraye: Adiso Therapeutics – DSMB. BMS – Advisory Committee/Board Member. Braintree Labs – Advisory Committee/Board Member. GSK – Advisory Committee/Board Member. IBD Educational Group – Advisory Committee/Board Member. Innovation Pharmaceuticals – Stock Options. Iterative Scopes – Advisory Committee/Board Member. Janssen – Advisory Committee/Board Member. Lilly – DSMB. Pfizer – Advisory Committee/Board Member. Sebela – Advisory Committee/Board Member. Theravance – DSMB.

Stephen Hanauer: Abbvie – Advisor or Review Panel Member, Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. allergan – Consultant, Grant/Research Support. Amgen – Consultant, Grant/Research Support. Arena – Advisor or Review Panel Member, Advisory Committee/Board Member. BMS – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. Boehringer-Ingelheim – Advisor or Review Panel Member, Advisory Committee/Board Member. gilead – Consultant, Grant/Research Support. gossamer – Advisor or Review Panel Member. gsk – Consultant, Grant/Research Support. Janssen – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. lilly – Grant/Research Support. Merck – Consultant. Novartis – Consultant. Pfizer – Advisor or Review Panel Member, Advisory Committee/Board Member, Speakers Bureau. prometheus – Advisory Committee/Board Member, Consultant, Grant/Research Support. Protagonist – Advisor or Review Panel Member, Advisory Committee/Board Member. seres – Consultant. seres therapeutics – Consultant. Takeda – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant, Speakers Bureau.

Parambir Dulai: BMS – Consultant. DigbiHealth – Stock Options. Gilead – Consultant. Janssen – Consultant. Lily – Consultant. Novartis – Consultant. Pfizer – Consultant, Grant/Research Support. PreciDiag – Royalties. Takeda – Consultant, Grant/Research Support.

Gursimran S. Kochhar, MD¹, Aakash Desai, MD², Raymond Cross, MD³, Francis A. Farraye, MD, MSc⁴, Stephen B. Hanauer, MD⁵, Parambir S. Dulai, MD⁵. A0389 - Risk of Tofacitinib-Related Adverse Events in Patients With Ulcerative Colitis: A Nationwide Propensity-Matched Cohort Study, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.