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Randomized Controlled Trial
. 2023 Jan 3;6(1):e2253570.
doi: 10.1001/jamanetworkopen.2022.53570.

Assessment of Quality of Life Among Patients With Recurrent Clostridioides difficile Infection Treated with Investigational Oral Microbiome Therapeutic SER-109: Secondary Analysis of a Randomized Clinical Trial

Kevin W Garey  1 , Jinhee Jo  1 , Anne J Gonzales-Luna  1 , Brittany Lapin  2 , Abhishek Deshpande  2 , Elaine Wang  3 , Brooke Hasson  3 , Sissi V Pham  4 , Shirley P Huang  4 , Pat Ray Reese  5 , Henry Wu  6 , Elizabeth Hohmann  7 , Paul Feuerstadt  8   9 , Caterina Oneto  10 , Charles S Berenson  11 , Christine Lee  12   13 , Barbara McGovern  3 , Lisa vonMoltke  3
Affiliations
Randomized Controlled Trial

Assessment of Quality of Life Among Patients With Recurrent Clostridioides difficile Infection Treated with Investigational Oral Microbiome Therapeutic SER-109: Secondary Analysis of a Randomized Clinical Trial

Kevin W Garey et al. JAMA Netw Open. .

Erratum in

  • Error in Visual Abstract.
    [No authors listed] [No authors listed] JAMA Netw Open. 2023 Feb 1;6(2):e234174. doi: 10.1001/jamanetworkopen.2023.4174. JAMA Netw Open. 2023. PMID: 36826823 Free PMC article. No abstract available.

Abstract

Importance: Recurrent Clostridioides difficile infection (CDI) is a debilitating disease leading to poor health-related quality of life (HRQOL), loss of productivity, anxiety, and depression. The potential association of treatment with HRQOL has not been well evaluated.

Objectives: To explore the association of SER-109 compared with placebo on HRQOL in patients with recurrent CDI up to week 8.

Design, setting, and participants: This study was a secondary analysis of a randomized, double-blind, placebo-controlled trial that took place at 56 sites in the US and Canada from July 2017 to April 2020 and included 182 patients randomized to SER-109 or placebo groups.

Interventions: SER-109 or placebo (4 capsules once daily for 3 days) following antibiotics for CDI.

Main outcomes and measures: Exploratory analysis of HRQOL using the disease specific Clostridioides difficile Quality of Life Survey (Cdiff32) assessed at baseline, week 1, and week 8.

Results: In this study, 182 patients (109 [59.9%] female; mean age, 65.5 [16.5] years) were randomized to SER-109 (89 [48.9%]) or placebo (93 [51.1%]) groups and were included in the primary and exploratory analyses. Baseline Cdiff32 scores were similar between patients in the SER-109 and placebo groups (52.0 [18.3] vs 52.8 [18.7], respectively). The proportion of patients with overall improvement from baseline in the Cdiff32 total score was higher in the SER-109 arm than placebo at week 1 (49.4% vs 26.9%; P = .012) and week 8 (66.3% vs 48.4%; P = .001).Greater improvements in total and physical domain and subdomain scores were observed in patients in the SER-109 group compared with placebo as early as week 1, with continued improvements observed at week 8. Among patients in the placebo group, improvements in HRQOL were primarily observed in patients with nonrecurrent CDI while patients in the SER-109 group reported improvements in HRQOL, regardless of clinical outcome.

Conclusions and relevance: In this secondary analysis of a phase 3 clinical trial, SER-109, an investigational microbiome therapeutic was associated with rapid and steady improvement in HRQOL compared with placebo through 8 weeks, an important patient-reported outcome.

Trial registration: ClinicalTrials.gov Identifier: NCT03183128.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Garey reported receiving grants from Seres Therapeutics during the conduct of the study and receiving grants from Summit, Acurx Pharmaceuticals, and Paratek Pharmaceuticals outside the submitted work. Dr Gonzales-Luna reported receiving grants from Seres Therapeutics during the conduct of the study. Dr Lapin reported receiving grants from Seres Therapeutics during the conduct of the study. Dr Deshpande reported receiving grants from Seres Therapeutics and Clorox and receiving personal fees from Merck as consultant outside the submitted work. Dr Hasson reported being a shareholder at Seres Therapeutics during the conduct of the study. Drs Pham, Huang, Reese, and Wu reported receiving personal fees from Seres Therapeutics during the conduct of the study. Dr Reese reported reporting for Aesara outside the submitted work. Dr Hohmann reported receiving grants from Seres and Tend during the conduct of the study, and receiving personal fees from Gilead Sciences, Kowa Pharmaceuticals America, and UptoDate unrelated authoring outside the submitted work. Dr Feuerstadt reported receiving grants from Seres Therapeutics during the conduct of the study and receiving personal fees from Seres Therapeutics, Ferring/Rebiotix, Summit Therapeutics Consulting, Takeda Pharmaceuticals outside the submitted work. Dr Oneto reported serving on the speaker’s bureau for Abbvie, BMS, Pfizer, and Salix and having research collaborations with Rebiotix, Seres Therapeutics, Abbvie, Salix, Intercept, Exact Sciences, Janssen, and Vedanta outside the submitted work. Dr Lee reported receiving grants from Rebiotix, Seres, Merck and Summit Therapeutics and serving on the advisory board at Rebitoix outside the submitted work. Dr McGovern reported being a stockholder of Seres Therapeutics during the conduct of the study. Dr von Moltke reported receiving personal fees from Seres Therapeutics during the conduct of the study and outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Change From Baseline at Week 1 and Week 8 in Cdiff32 Score by Treatment Group, ITT Population
P values above bars represent change from baseline within each treatment group. Brackets represent between treatment group comparisons. Cdiff32 indicates Clostridioides difficile Quality of Life Survey; ITT, intent to treat.
Figure 2.
Figure 2.. Week 8 Disease-Specific HRQOL Outcome Status (Defined by 10-Point Change) in Postbaseline Cdiff32 HRQOL Questionnaire by Treatment Arm, ITT Population
Week 8 disease-specific HRQOL outcome status, characterized as (1) improved, defined by an increase from baseline of at least 10 points; (2) unchanged, defined as a change from baseline of less than 10 points in either direction; or (3) worsened, defined by a decrease from baseline of at least 10 points, in Cdiff32 scores (total, mental, physical, and social/relationship domains) in SER-109 vs placebo treatment arms. Brackets represent between treatment group comparisons. Cdiff32 indicates Clostridioides difficile Quality of Life Survey; HRQOL, health-related quality-of-life; ITT, intent to treat.
Figure 3.
Figure 3.. Change in Cdiff32 HRQOL Score From Baseline to Week 8 by On-study Recurrence Status, ITT Population
P values above bars represent change from baseline within each treatment group. Brackets represent between treatment group comparisons. Cdiff32 indicates Clostridioides difficile Quality of Life Survey; HRQOL, health-related quality-of-life; ITT, intent to treat.
Figure 4.
Figure 4.. Change From Baseline at Week 8 in Cdiff32 HRQOL Questionnaire by On-study Recurrence Status in the Placebo and SER-109 Arms, ITT Population
P values above each bar represents change from baseline within each treatment group. Brackets represent between treatment group comparisons. Cdiff32 indicates Clostridioides difficile Quality of Life Survey; HRQOL, health-related quality-of-life; ITT, intent to treat.
See this image and copyright information in PMC

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