Lack of effectiveness of Bebtelovimab monoclonal antibody among high-risk patients with SARS-Cov-2 Omicron during BA.2, BA.2.12.1 and BA.5 subvariants dominated era

Sridhara et al., PLOS ONE, doi:10.1371/journal.pone.0279326

Sridhara et al., Lack of effectiveness of Bebtelovimab monoclonal antibody among high-risk patients with SARS-Cov-2 Omicron.., PLOS ONE, doi:10.1371/journal.pone.0279326

Apr 2023 Source PDF

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PSM retrospective 19,778 high-risk outpatients in the USA, showing no significant difference in outcomes with bebtelovimab treatment.

Confounding by treatment propensity. This study analyzes a population where only a fraction of eligible patients received the treatment. Patients receiving treatment may be more likely to follow other recommendations, more likely to receive additional care, and more likely to receive adjuvant treatments that are not tracked in the data (e.g., nasal/oral hygiene [c19early.org, c19early.org (B)], vitamin D [c19early.org (C)], etc.) — either because the physician recommending bebtelovimab also recommended them, or because the patient seeking out bebtelovimab is more likely to be familiar with the efficacy of additional treatments. Therefore, these kind of studies may overestimate the efficacy of treatments.

Efficacy is variant dependent. In Vitro research suggests a lack of efficacy for omicron BQ.1.1 [Planas].

1. c19early.org, https://c19early.org/p.

2. c19early.org (B), https://c19early.org/ph.

3. c19early.org (C), https://c19early.org/d.

4. Planas et al., bioRxiv, doi:10.1101/2022.11.17.516888, Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies, https://www.biorxiv.org/content/10.1101/2022.11.17.516888.

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risk of death, 85.7% lower, RR 0.14, p = 0.25, treatment 0 of 1,091 (0.0%), control 3 of 1,091 (0.3%), NNT 364, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), propensity score matching, day 30.

risk of death/hospitalization, 25.0% lower, HR 0.75, p = 0.31, treatment 24 of 1,091 (2.2%), control 28 of 1,091 (2.6%), adjusted per study, propensity score matching, multivariable, Cox proportional hazards.

risk of hospitalization, 11.1% lower, RR 0.89, p = 0.78, treatment 24 of 1,091 (2.2%), control 27 of 1,091 (2.5%), NNT 364, propensity score matching, day 30RETRO.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Sridhara et al., 28 Apr 2023, retrospective, USA, peer-reviewed, 13 authors, study period 5 April, 2022 - 1 August, 2022.

Contact: btanriover@arizona.edu.

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Lack of effectiveness of Bebtelovimab monoclonal antibody among high-risk patients with SARS-Cov-2 Omicron during BA.2, BA.2.12.1 and BA.5 subvariants dominated era

Srilekha Sridhara, Ahmet B Gungor, Halil K Erol, Mohanad Al-Obaidi, Tirdad T Zangeneh, Edward J Bedrick, Venkatesh K Ariyamuthu, Aneesha Shetty, Abd A Qannus, Katherine Mendoza, Sangeetha Murugapandian, Gaurav Gupta, Bekir Tanriover

PLOS ONE, doi:10.1371/journal.pone.0279326

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants are expected to be resistant to Bebtelovimab (BEB) monoclonal antibody (MAb) and the realworld experience regarding its effectiveness is scarce. This retrospective cohort study reports a data analysis in Banner Healthcare System (a large not-for-profit organization) between 4/5/2022 and 8/1/2022 and included 19,778 Coronavirus disease-19 (COVID-19) positive (by PCR or direct antigen testing) patients who were selected from Cerner-Electronic Health Record after the exclusions criteria were met. The study index date for cohort was determined as the date of BEB MAb administration or the date of the first positive COVID-19 testing. The cohort consist of COVID-19 infected patients who received BEB MAb (N = 1,091) compared to propensity score (PS) matched control (N = 1,091). The primary composite outcome was the incidence of 30-day all-cause hospitalization and/or mortality. All statistical analyses were conducted on the paired (matched) dataset. For the primary composite outcome, the event counts and percentages were reported. Ninety-five percent Clopper-Pearson confidence intervals for percentages were computed. The study cohorts were 1:1 propensity matched without replacement across 26 covariates using an optimal matching algorithm that minimizes the sum of absolute pairwise distance across the matched sample after fitting and using logistic regression as the distance function. The pairs were matched exactly on patient vaccination status, BMI group, age group and diabetes status. Compared to the PS matched control group (2.6%; 95% confidence interval [CI]: 1.7%, 3.7%), BEB MAb use (2.2%; 95% CI: 1.4%, 3.3%) did not significantly reduce the incidence

Writing -original draft: Srilekha Sridhara, Ahmet B. Gungor, Halil K. Erol, Mohanad Al-Obaidi, Tirdad T. Zangeneh, Venkatesh K. Ariyamuthu, Aneesha Shetty, Abd A. Qannus, Katherine Mendoza, Sangeetha Murugapandian, Gaurav Gupta, Bekir Tanriover.

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