D0354 - The Risk of Depression and All-Cause Mortality in Ulcerative Colitis Patients Maintained on Tofacitinib and Using Cannabis: A Population-Based Longitudinal Study

Tuesday, October 25, 2022

10:00 AM – 12:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

Sara Ghoneim, MD

University of Nebraska Medical Center
Omaha, NE

Sara Ghoneim, MD¹, Nabil El Hage Chehade, MD², Sherif Saleh, MD², Aun R. Shah, MD, MRCP¹, Faruq Pradhan, MD¹, Arnold Forlemu, MD¹, Pius Ekong, PhD³, Alexander T. Hewlett, DO¹
¹University of Nebraska Medical Center, Omaha, NE; ²MetroHealth Medical Center, Cleveland, OH; ³California Department of Public Health, Sacramento, CA

Introduction: Tofactinib is used to treat moderate-to-severe ulcerative colitis (UC). We aim to investigate the risk of major depressive disorder (MDD) in patients with UC using tofacitinib.

Methods: We queried a multicenter database (Explorys Inc) incorporating records from 26 major healthcare systems in the United States. Using systemized nomenclature of clinical medical terms (SNOMED-CT) adult patients diagnosed with UC from January 2010-November 2021 were identified. Among this cohort, race, gender, tofacitinib, cannabis, and tobacco use were examined. Primary and secondary outcomes were risk of MDD and all-cause mortality during December 2020-November 2021. Associations were estimated via gender-stratified multivariable logistic regression models. An interaction term was introduced to test the presence of effect modification.

Results: Out of 205540 adult patients diagnosed with UC, 3095 (1.51%) used cannabis and 37265 (18.13%) used tobacco. 360 UC patients were maintained on tofacitinib between 2018-2021. Among cannabis users, the prevalence of MDD was 9.05% (71.32% females, 28.67% males). UC patients with MDD had increased all-cause mortality compared to those without MDD, 1.11% vs 0.01%. After adjusting for confounding in the multivariate analysis, cannabis use was an independent risk factor for MDD adjusted odds ratio (aOR) 3.87 (95%CI: 3.94-4.43, P< 0.001). UC patients using tofacitinib had higher odds of MDD diagnosis aOR 3.78 (95%CI: 2.51-5.71, P< 0.001). Smokers had higher risk of MDD compared to nonsmokers aOR 1.91 (95%CI: 1.77-2.04, P< 0.001). Whites had significantly lower risk of MDD compared to non-whites aOR 0.85 (95%CI: 0.79-0.91, P< 0.001). Males had significantly lower risk of MDD compared to females aOR 0.54 (95%CI: 0.50-0.58, P< 0.001). However, males risk of MDD significantly increased if they were also cannabis users aOR 1.48 (95%CI: 1.14-1.93; P< 0.001). Compared to males, females with UC had higher risk of MDD if they were using tofacitinib aOR 5.39 (95%CI: 3.54-8.21, P< 0.001). Overall, all-cause mortality was significantly higher in UC patients with MDD aOR 54.98 (95%CI, 34.55-87.49, P< 0.001). The odds of death increased by 0.5% above baseline in UC patients with MDD if they were prescribed tofacitinib.

Discussion: Cannabis use among UC patients is strongly associated with a diagnosis of MDD. UC patients (especially females) using tofacitinib have higher odds of being diagnosed with MDD. All-cause mortality is higher in UC patients if they are diagnosed with MDD.

Figure: Figure. Multivariable logistic regression analysis of possible predictors for major depressive disorder (MDD) in patients with ulcerative colitis. Subgroup analysis stratified by gender. Forrest plot showing adjusted odds (OR); 95% confidence interval.

	MDD Diagnosis (N=1,495)			Absence of MDD Diagnosis (N=204,045)
Characteristics	Total (N)	Prevalence (%)	95% CI	Total (N)	Prevalence (%)	95% CI
Tofacitinib use
Yes	25	0.62	0.41-0.91	335	0.16	0.14-0.18
No	4,020	99.38	99.08-99.58	201,160	99.84	99.81-99.85
Cannabis use
Yes	280	6.92	6.17-7.74	2,815	1.39	1.34-1.44
No	3,765	93.07	92.25-93.82	198,680	98.61	98.55-98.65
Gender
Male	1,160	28.68	27.30-30.09	84,560	41.97	41.75-42.18
Female	2,885	71.32	69.90-72.69	116,935	58.03	57.81-58.24
Race
White	2,995	74.04	72.66-75.37	153,520	76.19	76.00-76.37
Non-White	1,050	25.96	24.62-27.33	47,975	23.81	23.62-23.99
Tobacco use
Yes	1,270	31.39	29.98-32.84	35,995	17.86	17.69-18.03
No	2,775	68.6	67.15-70.01	165,500	82.13	81.96-82.31
All-cause mortality
Yes	45	1.11	0.83-1.48	35	0.01	0.01-0.02
No	4,000	98.89	98.51-99.16	201,460	99.98	99.97-99.99

Table: Baseline characteristics of patients with ulcerative colitis included in the study. CI, confidence interval; MDD, major depressive disorder.

Disclosures:

Sara Ghoneim indicated no relevant financial relationships.

Nabil El Hage Chehade indicated no relevant financial relationships.

Sherif Saleh indicated no relevant financial relationships.

Aun Shah indicated no relevant financial relationships.

Faruq Pradhan indicated no relevant financial relationships.

Arnold Forlemu indicated no relevant financial relationships.

Pius Ekong indicated no relevant financial relationships.

Alexander Hewlett indicated no relevant financial relationships.

Sara Ghoneim, MD¹, Nabil El Hage Chehade, MD², Sherif Saleh, MD², Aun R. Shah, MD, MRCP¹, Faruq Pradhan, MD¹, Arnold Forlemu, MD¹, Pius Ekong, PhD³, Alexander T. Hewlett, DO¹. D0354 - The Risk of Depression and All-Cause Mortality in Ulcerative Colitis Patients Maintained on Tofacitinib and Using Cannabis: A Population-Based Longitudinal Study, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.