P0697 - Impact of Atovaquone and Proguanil on Steroid Use, Hospitalization, and Advanced Therapeutic Use in Patients With IBD: A Propensity Matched Cohort Study

Sunday, October 22, 2023

3:30 PM – 7:00 PM PT

Location: Exhibit Hall

Has Audio

Presenting Author(s)

Joseph David, MD

University of Arizona College of Medicine
Phoenix, AZ

Ahmed Nadeem, MD¹, Jaime A. Perez, PhD², Stephen B.. Hanauer, MD, FACG³, Parambir S. Dulai, MD⁴, William Sandborn, MD⁵, Aidan J. David, ⁶, Gregory Cooper, MD⁷, Jonathan Leighton, MD⁸, Miguel Regueiro, MD⁹, Emad Mansoor, MD¹⁰, Joseph David, MD¹¹
¹Cleveland Clinic, Cleveland, OH; ²University Hospitals Clinical Research Center, Cleveland, OH; ³Northwestern University Feinberg School of Medicine, Chicago, IL; ⁴Feinberg School of Medicine, Northwestern University, Chicago, IL; ⁵University of California, San Diego School of Medicine, La Jolla, CA; ⁶Case Western Reserve University, Cleveland, OH; ⁷Case Western Reserve/UHCMC, Cleveland, OH; ⁸Mayo Clinic College of Medicine, Scottsdale, AZ; ⁹Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH; ¹⁰Case Western Reserve University / University Hospitals, Cleveland, OH; ¹¹University of Arizona College of Medicine, Phoenix, AZ

Introduction: The prevalence of inflammatory bowel disease (IBD) is rising globally, and many patients don’t respond to or are intolerant of current therapies. Atovaquone and proguanil (A/P) are antimalarial agents long-used in combination to prevent and treat malaria. Atovaquone has recently been shown to be effective in healing DSS-induced murine colitis, and anecdotally in ulcerative colitis (UC) (by JD). We therefore sought to evaluate the impact of A/P on surrogates for IBD activity utilizing a large population database.

Methods: We performed a retrospective cohort study using TriNetX, a multi-institutional database to assess the effects of A/P on IBD patients. We identified all adult patients diagnosed with UC, Crohn’s disease (CD), and IBD (both UC & CD patients), between January 1, 2000 to December 31, 2020. Within each of these study populations, we stratified patients into two cohorts based on A/P use. For each of the three cohort comparisons, we performed 1:1 propensity score matching to balance cohorts on age, gender, race, comorbid conditions, and use of IBD advanced therapeutics to control for baseline disease severity.

The primary outcomes were steroid use (prednisone, methylprednisolone, budesonide), all-cause hospitalization, and advanced therapeutic use (immunomodulators, biologics, and small molecules) within 1 year indexed on first A/P exposure for the A/P cohort, or the diagnosis of UC, CD or IBD for the no A/P cohort.

Estimates of odds ratios (OR) and 95% confidence intervals (CI) were used to describe the outcome risks. P-values of α < 0.05 were considered statistically significant. Differences between groups were calculated using independent t-test or chi-square.

Results: After matching, we identified 361 CD, 407 UC and 905 IBD patients in each of their respective A/P and no A/P cohorts.

The A/P group had significantly lower odds of steroid use for CD (0.721) and IBD (0.654), and trended lower for UC (0.747) at 1 year compared to the no A/P group.

The A/P group had significantly lower odds of hospitalization for CD (0.176), UC (0.285) and IBD (0.242) at 1 year compared to the no A/P group.

The A/P group had significantly lower odds of advanced therapeutic use for CD (0.702) and IBD (0.700) and trended lower for UC (0.719) at 1 year compared to the no A/P group. (Table 1)

Discussion: This study provides real world data that A/P could have a protective effect in IBD patients and justifies clinical trials looking at repurposing A/P for the treatment of IBD.

Crohn’s Disease (n=361)
Outcome	No A/P	A/P	OR (CI)	p-Value
Steroid Use	132 (36.6%)	106 (29.4%)	0.721 (O.528, 0.985)	< 0.001
Hospitalization	79 (21.9%)	17 (4.7%)	0.176 (0.102, 0.305)	< 0.001
Advanced Therapeutic Use	97 (26.9%)	74 (20.5%)	0.702 (0.497, 0.991)	< 0.001
Ulcerative Colitis (n=407)
Outcome	No A/P	A/P	OR (CI)	p-Value
Steroid Use	136 (33.4%)	111 (27.3%)	0.747 (0.554, 1.009)	0.057
Hospitalization	68 (16.7%)	22 (5.4%)	0.285 (0.172, 0.471)	< 0.001
Advanced Therapeutic Use	51 (12.5%)	38 (9.3%)	0.719 (0.461, 1.121)	0.144
IBD (n=905)
Outcome	No A/P	A/P	OR (CI)	p-Value
Steroid Use	351 (38.8%)	265 (29.3%)	0.654 (0.537, 0.795)	< 0.001
Hospitalization	182 (20.1%)	52 (5.7%)	0.242 (0.175, 0.335)	< 0.001
Advanced Therapeutic Use	210 (23.2%)	158 (17.5%)	0.700 (0.556, 0.882)	0.002

Table: Table 1. Primary outcomes of steroid use, all-cause hospitalization and advanced therapeutic use within 1 year among CD, UC and All-IBD patients in the No A/P and A/P cohorts, after propensity score matching.

Disclosures:

Ahmed Nadeem indicated no relevant financial relationships.

Jaime Perez indicated no relevant financial relationships.

Stephen Hanauer: AbbVie – Consultant, Speakers Bureau. Allergan – Advisor or Review Panel Member, Consultant. Amgen – Consultant. arena – Advisor or Review Panel Member, Consultant. BMS – Advisor or Review Panel Member, Consultant, Speakers Bureau. Boehringer Ingelheim – Consultant, participating in Data and Safety Monitoring Boards. Celgene – Consultant. Celltrion – Consultant. Fresenius Kabi – Consultant. Genentech – Consultant, Grant/Research Support. Gilead – Consultant, Grant/Research Support. Gossamer – Advisor or Review Panel Member. GSK – Consultant, Grant/Research Support. InDex – Advisor or Review Panel Member. Intercept – Advisor or Review Panel Member. Janssen – Consultant, Speakers Bureau. Lilly – Consultant, Speakers Bureau. Merck – Consultant. Morphic – Consultant. Novartis – Consultant. Pfizer – Consultant, Speakers Bureau. Progenity – Consultant. Prometheus – Advisor or Review Panel Member, Consultant, Grant/Research Support. Protagonist – Advisor or Review Panel Member, Consultant. Salix – Consultant. Samsung Bioepis – Consultant. Seres – Consultant. Takeda – Consultant, Grant/Research Support, Speakers Bureau. TTL Pharma – Consultant. Ventyx – Advisor or Review Panel Member.

Parambir S. Dulai: Abbvie – Consultant. Abivax – Consultant. Adiso Therapeutics, Inc – Consultant. Bristol Myers Squibb – Consultant, Grant/Research Support. GlaxoSmithKline – Consultant. Janssen – Consultant, Grant/Research Support. Lilly – Consultant. Pfizer – Consultant, Grant/Research Support. PreciDiag – Royalties. Roivant – Consultant. Takeda – Consultant, Grant/Research Support.

William Sandborn: Abbvie – Consultant. Abivax – Consultant. Alfasigma – Consultant. Alimentiv – Consultant. BeiGene – Consultant, Stock-publicly held company(excluding mutual/index funds). Biora (Progenity) – Consultant, Spouse - stock, Stock-privately held company. Celltrion – Consultant. Forbion – Consultant. Genentech (Forbion) – Consultant. Gossamer Biosciences – Consultant, Stock-publicly held company(excluding mutual/index funds). Index Pharmaceuticals – Consultant. Iveric Bio – Spouse - consultant, stock options. Prometheus Biosciences – Advisory Committee/Board Member, Consultant, Spouse - employee, stock, stock options, Stock Options, Stock-publicly held company(excluding mutual/index funds). Prometheus Laboratories – Advisory Committee/Board Member, Consultant, Spouse - stock, stock options, Stock Options, Stock-privately held company. Protagonists Therapeutics – Consultant. Shoreline Biosciences – Advisory Committee/Board Member, Consultant, Employee, Stock-privately held company. Ventyx Biosciences – Advisory Committee/Board Member, Consultant, Employee, Spouse - stock, stock options, Stock Options, Stock-publicly held company(excluding mutual/index funds). Vimalan – Consultant, Spouse - stock, stock options, Stock-privately held company. Vivreon Gastrosciences – Consultant, Stock-privately held company.

Aidan David indicated no relevant financial relationships.

Gregory Cooper indicated no relevant financial relationships.

Jonathan Leighton: ANX – Advisor or Review Panel Member. Braintree – Advisor or Review Panel Member. Fresenius Kabi – Advisor or Review Panel Member. SEI Healthcare – Advisor or Review Panel Member.

Miguel Regueiro: AbbVie – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Alfasigma – Advisory Committee/Board Member, Consultant. Allergan – Advisory Committee/Board Member, Consultant. Amgen – Advisory Committee/Board Member, Consultant. Bristol Myers Squibb – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Celgene – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Eli Lilly – Advisory Committee/Board Member, Consultant. Genentech – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Gilead Sciences – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Janssen – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Miraca Labs – Advisory Committee/Board Member, Consultant. Pfizer Inc – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Prometheus – Advisory Committee/Board Member, Consultant. Salix – Advisory Committee/Board Member, Consultant. Seres – Advisory Committee/Board Member, Consultant. Takeda – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Target RWE – Advisory Committee/Board Member, Consultant. UCB – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Wolters Kluwer Health – Royalties.

Emad Mansoor indicated no relevant financial relationships.

Joseph David indicated no relevant financial relationships.

Ahmed Nadeem, MD¹, Jaime A. Perez, PhD², Stephen B.. Hanauer, MD, FACG³, Parambir S. Dulai, MD⁴, William Sandborn, MD⁵, Aidan J. David, ⁶, Gregory Cooper, MD⁷, Jonathan Leighton, MD⁸, Miguel Regueiro, MD⁹, Emad Mansoor, MD¹⁰, Joseph David, MD¹¹. P0697 - Impact of Atovaquone and Proguanil on Steroid Use, Hospitalization, and Advanced Therapeutic Use in Patients With IBD: A Propensity Matched Cohort Study, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.