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Effect of Endogenous Clostridioides difficile Toxin Antibodies on Recurrence of C. difficile Infection.

Abstract

BACKGROUND

Endogenous antibodies (eAbs) against Clostridioides (Clostridium) difficile toxins may protect against recurrence of C. difficile infection (rCDI). This hypothesis was tested using placebo group data from MODIFY (Monoclonal Antibodies for C. difficile Therapy) I and II (NCT01241552 and NCT01513239, respectively), global, randomized phase 3 trials that assessed the efficacy and safety of the antitoxin monoclonal antibodies bezlotoxumab and actoxumab in participants receiving antibiotic therapy for CDI.

METHODS

A placebo infusion (normal saline) was administered on study day 1. Serum samples were collected on day 1, week 4, and week 12, and eAb-A and eAb-B titers were measured by 2 validated electrochemiluminescence immunoassays. Rates of initial clinical cure and rCDI were summarized by eAb titer category (low, medium, high) at each time point.

RESULTS

Serum eAb titers were available from a total of 773 participants. The proportion of participants with high eAb-A and eAb-B titers increased over time. Rates of initial clinical cure were similar across eAb titer categories. There was no correlation between eAb-A titers and rCDI rate at any time point. However, there was a negative correlation between rCDI and eAb-B titer on day 1 and week 4. rCDI occurred in 22% of participants with high eAb-B titers at baseline compared with 35% with low or medium titers (P = .015).

CONCLUSIONS

Higher eAb titers against toxin B, but not toxin A, were associated with protection against rCDI. These data are consistent with the observed efficacy of bezlotoxumab, and lack of efficacy of actoxumab, in the MODIFY trials.High titers of endogenous antibodies to Clostridioides difficile toxin B, but not toxin A, were associated with reduced recurrence of C. difficile infection. These findings are consistent with efficacy data from the phase 3 MODIFY trials of bezlotoxumab and actoxumab.

Authors+Show Affiliations

Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.University of Edinburgh, Edinburgh, United Kingdom.Merck & Co., Inc., Kenilworth, New Jersey.Leeds Teaching Hospitals and University of Leeds, United Kingdom.Loyola University Chicago Stritch School of Medicine, Maywood, and. Edward Hines Jr Veterans Affairs Hospital, Hines, Illinois.Merck & Co., Inc., Kenilworth, New Jersey.Merck & Co., Inc., Kenilworth, New Jersey.Merck & Co., Inc., Kenilworth, New Jersey.Merck & Co., Inc., Kenilworth, New Jersey.Merck & Co., Inc., Kenilworth, New Jersey.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31628838

Citation

Kelly, Ciarán P., et al. "Effect of Endogenous Clostridioides Difficile Toxin Antibodies On Recurrence of C. Difficile Infection." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, 2019.
Kelly CP, Poxton IR, Shen J, et al. Effect of Endogenous Clostridioides difficile Toxin Antibodies on Recurrence of C. difficile Infection. Clin Infect Dis. 2019.
Kelly, C. P., Poxton, I. R., Shen, J., Wilcox, M. H., Gerding, D. N., Zhao, X., ... Dorr, M. B. (2019). Effect of Endogenous Clostridioides difficile Toxin Antibodies on Recurrence of C. difficile Infection. Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, doi:10.1093/cid/ciz809.
Kelly CP, et al. Effect of Endogenous Clostridioides Difficile Toxin Antibodies On Recurrence of C. Difficile Infection. Clin Infect Dis. 2019 Oct 19; PubMed PMID: 31628838.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of Endogenous Clostridioides difficile Toxin Antibodies on Recurrence of C. difficile Infection. AU - Kelly,Ciarán P, AU - Poxton,Ian R, AU - Shen,Judong, AU - Wilcox,Mark H, AU - Gerding,Dale N, AU - Zhao,Xuemei, AU - Laterza,Omar F, AU - Railkar,Radha, AU - Guris,Dalya, AU - Dorr,Mary Beth, Y1 - 2019/10/19/ PY - 2019/03/13/received PY - 2019/09/30/accepted PY - 2019/10/20/entrez PY - 2019/10/20/pubmed PY - 2019/10/20/medline KW - Clostridioides difficile KW - Clostridium difficile KW - bezlotoxumab KW - endogenous antibodies KW - recurrence JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JO - Clin. Infect. Dis. N2 - BACKGROUND: Endogenous antibodies (eAbs) against Clostridioides (Clostridium) difficile toxins may protect against recurrence of C. difficile infection (rCDI). This hypothesis was tested using placebo group data from MODIFY (Monoclonal Antibodies for C. difficile Therapy) I and II (NCT01241552 and NCT01513239, respectively), global, randomized phase 3 trials that assessed the efficacy and safety of the antitoxin monoclonal antibodies bezlotoxumab and actoxumab in participants receiving antibiotic therapy for CDI. METHODS: A placebo infusion (normal saline) was administered on study day 1. Serum samples were collected on day 1, week 4, and week 12, and eAb-A and eAb-B titers were measured by 2 validated electrochemiluminescence immunoassays. Rates of initial clinical cure and rCDI were summarized by eAb titer category (low, medium, high) at each time point. RESULTS: Serum eAb titers were available from a total of 773 participants. The proportion of participants with high eAb-A and eAb-B titers increased over time. Rates of initial clinical cure were similar across eAb titer categories. There was no correlation between eAb-A titers and rCDI rate at any time point. However, there was a negative correlation between rCDI and eAb-B titer on day 1 and week 4. rCDI occurred in 22% of participants with high eAb-B titers at baseline compared with 35% with low or medium titers (P = .015). CONCLUSIONS: Higher eAb titers against toxin B, but not toxin A, were associated with protection against rCDI. These data are consistent with the observed efficacy of bezlotoxumab, and lack of efficacy of actoxumab, in the MODIFY trials.High titers of endogenous antibodies to Clostridioides difficile toxin B, but not toxin A, were associated with reduced recurrence of C. difficile infection. These findings are consistent with efficacy data from the phase 3 MODIFY trials of bezlotoxumab and actoxumab. SN - 1537-6591 UR - https://www.unboundmedicine.com/medline/citation/31628838/Effect_of_Endogenous_Clostridioides_difficile_Toxin_Antibodies_on_Recurrence_of_C._difficile_Infection L2 - https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/ciz809 DB - PRIME DP - Unbound Medicine ER -