P0698 - Atovaquone and Proguanil vs Hepatitis A Vaccine, Hydroxychloroquine, and Mesalamine in Patients With IBD: A Propensity Score Matched Cohort Comparison of Strategically Selected Comparators

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 more treatment options are needed. Atovaquone and proguanil (A/P) are medications long-used in combination to prevent and treat malaria. A/P is most commonly prescribed prior to travel to endemic areas. Atovaquone has been shown to be effective in healing DSS-induced murine colitis; anecdotal clinical reports (JD) and a recent database study have suggested a possible protective effect of A/P in a cohort of IBD patients. We sought to compare the impact of A/P to strategically selected comparators on surrogates for IBD activity.

Methods: We performed a retrospective cohort study using TriNetX, a multi-institutional database, to compare the effects of A/P with hepatitis A vaccine (HAV), hydroxychloroquine (HCQ), and mesalamine (MES) in IBD patients. HAV was chosen to match the cohorts on being healthy enough to travel, HCQ as another antimalarial, and MES as an IBD standard of care comparator.

We identified all adult patients diagnosed with IBD from January 1, 2000 to December 31, 2019 and stratified them into 3 distinct comparison groups based on A/P use vs. HAV, HCQ, and MES. We performed 1:1 propensity score matching to balance cohorts on age, gender, race, comorbid conditions, and use of IBD advanced therapeutics.

The primary outcomes were steroid use (prednisone, methylprednisolone, budesonide), all-cause hospitalization, and advanced therapeutic use (immunomodulators, biologics, small molecules) within 1 year indexed on first exposure to the respective drugs being compared.

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 633 patients with A/P vs. HAV, 770 with A/P vs. HCQ, and 472 with A/P vs. MES and followed them for 1 year post initial exposure. The A/P group had significantly lower odds of steroid use vs. HAV (0.529), HCQ (0.425), and MES (0.476); hospitalization vs. HAV (0.346), HCQ (0.484), and MES (0.276); and advanced therapeutic use vs. HAV (0.326), HCQ (0.605), and MES (0.487). (Table 1)

Discussion: This study builds on prior real world data suggesting a protective effect of A/P in IBD patients, showing the effect persisted when compared to strategically selected comparators, and further justifies clinical trials looking at repurposing A/P for the treatment of IBD.

A/P vs HAV (n=633)
Outcome	HAV	A/P	OR (CI)	p-Value
Steroid use	275 (43.4%)	183 (28.9%)	0.529 (0.419, 0.668)	< 0.001
Hospitalization	94 (14.8%)	36 (5.7%)	0.346 (0.231, 0.517)	< 0.001
Advanced Therapeutic use	258 (25.8%)	116 (18.3%)	0.326 (0.252, 0.421)	< 0.001
A/P vs HCQ (n=770)
Outcome	HCQ	A/P	OR (CI)	p-Value
Steroid use	396 (51.4%)	239 (31%)	0.425 (0.345, 0.523)	< 0.001
Hospitalization	93 (12.1%)	48 (6.2%)	0.484 (0.336, 0.696)	< 0.001
Advanced Therapeutic use	220 (28.6%)	150 (19.5%)	0.605 (0.477, 0.767)	< 0.001
A/P vs MES (n=472)
Outcome	MES	A/P	OR (CI)	p-Value
Steroid use	223 (47.2%)	141 (29.9%)	0.476 (0.364, 0.621)	< 0.001
Hospitalization	85 (18%)	27 (5.7%)	0.276 (0.175, 0.435)	< 0.001
Advanced Therapeutic use	132 (28%)	75 (15.9%)	0.487 (0.354, 0.669)	< 0.001

Table: Table 1. Primary outcomes of steroid use, all-cause hospitalization and advanced therapeutic use within 1 year among IBD patients using A/P compared with hepatitis A vaccine (HAV), hydroxychloroquine (HCQ), and mesalamine (MES) 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. P0698 - Atovaquone and Proguanil vs Hepatitis A Vaccine, Hydroxychloroquine, and Mesalamine in Patients With IBD: A Propensity Score Matched Cohort Comparison of Strategically Selected Comparators, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.