Real-world Effectiveness and Tolerability of Monoclonal Antibody Therapy for Ambulatory Patients With Early COVID-19
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Abstract
Background
Neutralizing monoclonal antibodies (MAbs) are a promising therapy for early coronavirus disease 2019 (COVID-19), but their effectiveness has not been confirmed in a real-world setting.
Methods
In this quasi-experimental pre-/postimplementation study, we estimated the effectiveness of MAb treatment within 7 days of symptom onset in high-risk ambulatory adults with COVID-19. The primary outcome was a composite of emergency department visits or hospitalizations within 14 days of positive test. Secondary outcomes included adverse events and 14-day mortality. The average treatment effect in the treated for MAb therapy was estimated using inverse probability of treatment weighting and the impact of MAb implementation using propensity-weighted interrupted time series analysis.
Results
Pre-implementation (July–November 2020), 7404 qualifying patients were identified. Postimplementation (December 2020–January 2021), 594 patients received MAb treatment and 5536 did not. The primary outcome occurred in 75 (12.6%) MAb recipients, 1018 (18.4%) contemporaneous controls, and 1525 (20.6%) historical controls. MAb treatment was associated with decreased likelihood of emergency care or hospitalization (odds ratio, 0.69; 95% CI, 0.60–0.79). After implementation, the weighted probability that a given patient would require an emergency department visit or hospitalization decreased significantly (0.7% per day; 95% CI, 0.03%–0.10%). Mortality was 0.2% (n = 1) in the MAb group compared with 1.0% (n = 71) and 1.0% (n = 57) in pre- and postimplementation controls, respectively. Adverse events occurred in 7 (1.2%); 2 (0.3%) were considered serious.
Conclusions
MAb treatment of high-risk ambulatory patients with early COVID-19 was well tolerated and likely effective at preventing the need for subsequent emergency department or hospital care.
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SciScore for 10.1101/2021.03.15.21253646: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Clinical eligibility for MAb was defined by the CSC committee as the following: 1) at or above the risk score threshold (set at ≥7.5 points, which identified approximately the top decile of estimated risk among COVID-19 positive patients), 2) laboratory-confirmed COVID-19 by nucleic acid amplification test or antigen detection, 3) symptomatic disease with symptom onset within no more than 7 days. Randomization To aid in comparing these results to those from randomized trials, we used the Chatellier method of estimating the number needed to treat (NNT) from the odds ratio. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. SciScore for 10.1101/2021.03.15.21253646: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Clinical eligibility for MAb was defined by the CSC committee as the following: 1) at or above the risk score threshold (set at ≥7.5 points, which identified approximately the top decile of estimated risk among COVID-19 positive patients), 2) laboratory-confirmed COVID-19 by nucleic acid amplification test or antigen detection, 3) symptomatic disease with symptom onset within no more than 7 days. Randomization To aid in comparing these results to those from randomized trials, we used the Chatellier method of estimating the number needed to treat (NNT) from the odds ratio. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Setting and Data Repository: Intermountain Healthcare is a regional integrated healthcare system that provides care to more than 1.5 million patients each year. Intermountain Healthcaresuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our study has several limitations. First, despite a target trial emulation design and complementary causal inference analyses, it is impossible to fully mitigate biases inherent to observational data. We recognize that in the post-implementation group, unmeasurable or unmeasured confounding factors may influence the estimates for counterfactual treatment effect. This is addressed by the interrupted time series analysis, and we are reassured that this complementary analysis does corroborate the ATT estimate. However, it is possible that unmeasured factors influenced these estimates. Although such interventions are uncommon for ambulatory patients in our health system, we were unable to measure concomitant prescription of other repurposed therapies such as corticosteroids. In addition, date of symptom onset was not available precluding use as inclusion criterion for control group patients. Although our integrated health system provides care for more than two-thirds of all COVID-19 hospitalizations in our region, it is possible that some patients may have been admitted to an ED or hospital outside of our system after testing, resulting in outcome misclassification. Despite intentional and programmatic efforts at both the state and integrated healthcare network level to address healthcare disparities in MAb delivery, we did observe a significantly lower rate of MAb infusion to patients from communities of color. This can be partially understood by the dramatic intercurrent declin...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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