A0084 - Outcomes of Patients Receiving Bezlotoxumab for the Prevention of Recurrent Clostridioides difficile Infection – A Multicenter Study

Sunday, October 23, 2022

5:00 PM – 7:00 PM ET

Location: Crown Ballroom

Has Audio

Presenting Author(s)

Abdelkader Chaar, MD

Yale University School of Medicine
New Haven, CT

Award: Presidential Poster Award

Abdelkader Chaar, MD¹, John Damianos, MD¹, Rabia Rizwan, MD¹, Ahmad Nawaz, MD¹, Paul Feuerstadt, MD, FACG²
¹Yale University School of Medicine, New Haven, CT; ²PACT Gastroenterology Center and Yale University School of Medicine, New Haven, CT

Introduction: Clostridioides difficile infection (CDI) is the most common healthcare-associated infection in the United States (US). Treatment guidelines have evolved resulting in better outcomes however recurrent disease remains a major issue associated with significant morbidity despite best practices. Bezlotoxumab (BEZ) is a fully humanized monoclonal antibody approved by FDA in 2017 for prevention of recurrent CDI (rCDI). Limited real-world data are available regarding BEZ usage outside of clinical trials. In this multicenter study, we aim to report our experience with BEZ at a large healthcare system in northeast US.

Methods: We retrospectively reviewed all consecutive adult patients who received BEZ from 1/2017 until 12/2021 at Yale-New Haven Health System and had at least 90 days of follow up. Data collected for each patient included demographics, medical co-morbidities, adverse events to BEZ and rates of rCDI following BEZ.

Results: A total of 114 patients were included with a mean age of 67.3 years (range 25-97); 74 (64.9%) were female. There has been a recent increased utilization of BEZ with more than half of our sample (n=73, 64%) being since the beginning of COVID-19 pandemic and 38.6% in 2021 alone. Most patients were treated with vancomycin (88.6%) while 11 (9.7%) received fidaxomicin. Median time from most recent CDI episode to BEZ infusion was 22.5 days. Notably, 17.5% were not on active CDI treatment when they received BEZ. 30 (26.3%) received BEZ after initial CDI, 52 (45.6%) had one prior recurrent episode while 32 (28.1%) had 2 or more previous recurrences. Among those who received BEZ, 10 patients (8.8%) experienced 90-day rCDI, of these 9 (90%) had history of at least 1 episode of rCDI. There were no statistically significant differences in baseline characteristics between r-CDI and non-rCDI groups (Table 1). Furthermore, no statistical difference in rCDI between those who were on CDI treatment at the time of BEZ and those who completed it before BEZ [9/94 (9.6%) vs 1/20 (5.0%); p=0.511].

Discussion: Our real-life data confirms that Bezlotoxumab appears to be safe and effective in preventing rCDI in this population whether given during CDI treatment or after. BEZ represents an important treatment option in this highly morbid population. Further studies are needed to determine the benefit of early administration of BEZ after index CDI in those at risk and to consider utilization shifts following the 2021 ACG updated guideline recommendations advising it’s usage.

Variable	All patients (N=114)	90-Day Recurrent CDI		p-value
Variable	All patients (N=114)	Yes (n=10)	No (n=104)	p-value
Age (years), mean ± SD	67.3 ± 14.3	67.2 ± 13.2	67.3 ± 14.4	0.936
Age (years), median [range]	68.5 [25 – 97]	67.5 [42 – 86]	69 [25 – 97]	0.936
Female, n (%)	74 (64.9)	7 (70.0)	67 (64.4)	0.724
Race, n (%)				0.048
White	96 (84.2)	7 (70)	89 (85.6)
African American	9 (7.9)	3 (30.0)	6 (5.8)
Asian	1 (0.9)	0 (0.0)	1 (1.0)
Unknown	8 (7.0)	0 (0.0)	8 (7.7)
Risk factors for recurrent CDI
Age ≥ 65 years, n (%)	67 (58.8)	6 (60.0)	61 (58.65)	0.934
Co-morbidities / Immunosuppression, n (%)
Active malignancy on chemotherapy	28 (24.6)	3 (30.0)	25 (24.0)	0.676
Organ transplant	27 (23.7)	3 (30.0)	24 (23.1)	0.623
On high dose steroids	4 (3.5)	1 (10.0)	3 (2.9)	0.243
Biologics/Immunomodulators	6 (5.3)	1 (10.0)	5 (4.8)	0.482
Hemodialysis	9 (7.9)	2 (20.0)	7 (6.7)	0.137
History of heart failure, n (%)	36 (31.6)	4 (40.0)	32 (30.8)	0.549
Charlson co-morbidity index, mean ± SD	4.9 ± 2.5	4.1 ± 2.0	4.9 ± 2.6	0.271
Charlson co-morbidity index ≥3, n (%)	91 (79.8)	8 (80.0)	83 (79.8)	0.988
Treatment of most recent CDI episode, n (%)				0.738
Vancomycin fixed dose	35 (31.0)	3 (30.0)	32 (31.1)
Vancomycin taper	60 (53.1)	6 (60.0)	54 (52.4)
Fidaxomicin	11 (9.73)	0 (0.0)	11 (10.7)
Vancomycin taper + Nitazoxanide	4 (3.5)	1 (10.0)	3 (2.9)
Vancomycin + Fidaxomicin	2 (1.8)	0 (0.0)	2 (1.9)
Vancomycin chronic suppressive therapy	1 (.09)	0 (0.0)	1 (1.1)
Received BEZ while on CDI treatment, n (%)				0.511
Yes	94 (82.5)	9 (90.0)	85 (81.7)
No	20 (17.5)	1 (10.0)	19 (18.3)
Days from most recent CDI to BEZ, median [range]	22.5 [4 – 426]	20 [7 – 69]	22 [4 – 426]	0.904
Days from starting SoC to BEZ median [range]	21 [3 – 211]	16 [7 – 67]	21.5 [3 – 211]	0.740
CDI history
Primary CDI	30 (26.3)	1 (10.0)	29 (27.9)	0.220
No. of CDI recurrences ever
1	52 (45.6)	6 (60.0)	46 (44.2)	0.339
≥2	32 (28.1)	3 (30.0)	29 (27.9)	0.887
Time to recurrence (days), median [range]	--	35 [4 – 76]		--
Adverse events to BEZ	· 1 Patient experienced mild allergic reaction (tongue swelling, itching and headache), required monitoring in the ED for less than 24 hours. · 1 Patient admitted with CHF exacerbation within 30 days of BEZ (although felt to be due to non-compliance with diuretics).
90-day recurrent CDI following BEZ	10 (8.8)			--
Year of BEZ administration
2017	7 (6.1)			--
2018	11 (6.6)			--
2019	26 (22.8)			--
2020	26 (22.8)			--
2021	44 (38.6)			--

Table: Table 1: Baseline variables comparing recurrent CDI patients and nonrecurrent patients after a single dose of Bezlotoxumab.
Abbreviations: BEZ: Bezlotoxumab, SoC: Standard of care, CDI: Clostridioides difficile infection, SD: Standard deviation

Disclosures:

Abdelkader Chaar indicated no relevant financial relationships.

John Damianos indicated no relevant financial relationships.

Rabia Rizwan indicated no relevant financial relationships.

Ahmad Nawaz indicated no relevant financial relationships.

Paul Feuerstadt: Ferring/Rebiotix Pharmaceuticals – Advisory Committee/Board Member, Consultant, Speakers Bureau. Merck and Co – Consultant. Seres Therapeutics – Advisory Committee/Board Member, Consultant. Takeda Pharmaceuticals – Advisory Committee/Board Member.

Abdelkader Chaar, MD¹, John Damianos, MD¹, Rabia Rizwan, MD¹, Ahmad Nawaz, MD¹, Paul Feuerstadt, MD, FACG². A0084 - Outcomes of Patients Receiving Bezlotoxumab for the Prevention of Recurrent Clostridioides difficile Infection – A Multicenter Study, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.