Tixagevimab/cilgavimab for COVID-19: real-time analysis of all 7 studies

Tixagevimab/cilgavimab for COVID-19: real-time meta analysis of 6 studies

Covid Analysis (Preprint) (meta analysis)

• Statistically significant improvements are seen for mortality, hospitalization, and cases. 5 studies from 5 independent teams in 2 different countries show statistically significant improvements in isolation (3 for the most serious outcome).

• Meta analysis using the most serious outcome reported shows 46% [17‑64%] improvement. Results are slightly worse for Randomized Controlled Trials and similar for peer-reviewed studies.

• Efficacy is variant dependent. In Vitro research suggests a lack of efficacy for omicron BA.2 [Zhou], however [Kertes] show significant efficacy with omicron. Monoclonal antibody use with variants can be associated with prolonged viral loads, clinical deterioration, and immune escape [Choudhary].

• While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 17% of tixagevimab/cilgavimab studies show zero events in the treatment arm. Multiple treatments are typically used in combination, and other treatments may be more effective.

• No treatment, vaccine, or intervention is 100% available and effective for all variants. All practical, effective, and safe means should be used. Denying the efficacy of treatments increases mortality, morbidity, collateral damage, and endemic risk.

• All data to reproduce this paper and sources are in the appendix.

Covid Analysis et al., 8/12/2022, preprint, 1 author.

Association between AZD7442 (tixagevimab-cilgavimab) administration and SARS-CoV-2 infection, hospitalization and mortality

Kertes et al., Clinical Infectious Diseases, doi:10.1093/cid/ciac625

Retrospective 825 immunocompromised individuals treated with tixagevimab-cilgavimab and 4229 untreated in Israel, showing significantly lower infection and hospitalization/death with treatment. Omicron was the dominant variant.

risk of death/hospitalization, 91.9% lower, RR 0.08, p = 0.01, treatment 1 of 825 (0.1%), control 63 of 4,299 (1.5%), NNT 74, adjusted, OR converted to RR, multivariable.

risk of case, 47.1% lower, RR 0.53, p = 0.01, treatment 29 of 825 (3.5%), control 308 of 4,299 (7.2%), NNT 27, adjusted, OR converted to RR, multivariable.

Kertes et al., 7/29/2022, retrospective, Israel, peer-reviewed, 10 authors.

Tixagevimab–cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial

Holland et al., The Lancet Respiratory Medicine, doi:10.1016/S2213-2600(22)00215-6

RCT with 710 hospitalized patients treated with tixagevimab/cilgavimab, and 707 placebo patients, showing lower mortality with treatment.

risk of death, 30.0% lower, RR 0.70, p = 0.03, treatment 61 of 710 (8.6%), control 86 of 707 (12.2%), NNT 28, day 90.

risk of no recovery, 7.4% lower, RR 0.93, p = 0.21, treatment 710, control 707, sustained recovery, day 90, primary outcome.

Holland et al., 7/8/2022, Double Blind Randomized Controlled Trial, placebo-controlled, USA, peer-reviewed, 103 authors, study period 10 February, 2021 - 30 September, 2021, trial NCT04501978 (history) (ACTIV-3-TICO).

Efficacy and safety of intramuscular administration of tixagevimab–cilgavimab for early outpatient treatment of COVID-19 (TACKLE): a phase 3, randomised, double-blind, placebo-controlled trial

Montgomery et al., The Lancet Respiratory Medicine, doi:10.1016/S2213-2600(22)00180-1

RCT 910 outpatients in the USA, 456 treated with tixagevimab/cilgavimab, showing significantly lower combined severe COVID-19/death with treatment.

risk of death, 0.2% lower, RR 1.00, p = 1.00, treatment 6 of 452 (1.3%), control 6 of 451 (1.3%), NNT 33975, all cause mortality.

risk of severe case, 50.4% lower, RR 0.50, p = 0.010, treatment 18 of 407 (4.4%), control 37 of 415 (8.9%), NNT 22, primary outcome.

risk of hospitalization, 56.7% lower, RR 0.43, p = 0.002, treatment 17 of 413 (4.1%), control 40 of 421 (9.5%), NNT 19.

Montgomery et al., 6/7/2022, Double Blind Randomized Controlled Trial, placebo-controlled, USA, peer-reviewed, mean age 46.0, 20 authors, study period 28 January, 2021 - 22 July, 2021, trial NCT04723394 (history) (TACKLE).

Tixagevimab/Cilgavimab for Prevention of COVID-19 during the Omicron Surge: Retrospective Analysis of National VA Electronic Data

Young-Xu et al., medRxiv, doi:10.1101/2022.05.28.22275716 (Preprint)

PSM retrospective 1,848 immunocompromised patients given tixagevimab/cilgavimab prophylaxis, showing lower mortality, hospitalization, and cases.

risk of death, 64.0% lower, HR 0.36, p = 0.004, treatment 1,733, control 6,354.

risk of death/hospitalization/cases, 69.0% lower, HR 0.31, p < 0.001, treatment 17 of 1,733 (1.0%), control 206 of 6,354 (3.2%), NNT 44.

risk of hospitalization, 87.0% lower, HR 0.13, p = 0.04, treatment 1,733, control 6,354.

risk of case, 66.0% lower, HR 0.34, p = 0.03, treatment 1,733, control 6,354.

Young-Xu et al., 5/29/2022, retrospective, propensity score matching, USA, preprint, 10 authors.

Intramuscular AZD7442 (Tixagevimab–Cilgavimab) for Prevention of Covid-19

Levin et al., New England Journal of Medicine, doi:10.1056/NEJMoa2116620

PrEP RCT with 3,441 tixagevimab/cilgavimab patients and 1,731 control patients, showing lower risk of symptomatic cases with treatment.

risk of death, 85.7% lower, RR 0.14, p = 0.11, treatment 0 of 3,441 (0.0%), control 2 of 1,731 (0.1%), NNT 866, relative risk is not 0 because of continuity correction due to zero events.

risk of symptomatic case, 82.1% lower, RR 0.18, p < 0.001, treatment 11 of 3,441 (0.3%), control 31 of 1,731 (1.8%), NNT 68, 6 months.

risk of symptomatic case, 76.3% lower, RR 0.24, p < 0.001, treatment 8 of 3,441 (0.2%), control 17 of 1,731 (1.0%), NNT 133, median 83 days followup.

Levin et al., 4/20/2022, Double Blind Randomized Controlled Trial, placebo-controlled, multiple countries, peer-reviewed, 24 authors, study period 21 November, 2020 - 22 March, 2021, trial NCT04625725 (history) (PROVENT).

Fact sheet for healthcare providers: emergency use authorization for Evusheld (tixagevimab co-packaged with cilgavimab)

FDA (Preprint)

PEP RCT with 749 tixagevimab/cilgavimab patients and 372 control patients, showing lower risk of symptomatic cases with treatment, without statistical significance. STORM CHASER. NCT04625972.

risk of symptomatic case, 39.5% lower, RR 0.60, p = 0.07, treatment 28 of 749 (3.7%), control 23 of 372 (6.2%), NNT 41, from graph, day 180.

risk of symptomatic case, 32.8% lower, RR 0.67, p = 0.23, treatment 23 of 749 (3.1%), control 17 of 372 (4.6%), NNT 67.

FDA et al., 12/8/2021, Double Blind Randomized Controlled Trial, placebo-controlled, multiple countries, preprint, 1 author, trial NCT04625972 (history).

PROVENT: Phase 3 Study of Efficacy and Safety of AZD7442 (Tixagevimab/Cilgavimab) for Pre-exposure Prophylaxis of COVID-19 in Adults

Levin et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofab466.1646 (Preprint)

PrEP RCT with 3,441 tixagevimab/cilgavimab patients and 1,731 control patients, showing lower risk of symptomatic cases with treatment. Followup data is from [fda.gov].

1. fda.gov, https://www.fda.gov/media/154701/download.

risk of death, 85.7% lower, RR 0.14, p = 0.11, treatment 0 of 3,441 (0.0%), control 2 of 1,731 (0.1%), NNT 866, relative risk is not 0 because of continuity correction due to zero events.

risk of symptomatic case, 76.3% lower, RR 0.24, p < 0.001, treatment 8 of 3,441 (0.2%), control 17 of 1,731 (1.0%), NNT 133.

Levin et al., 12/8/2021, Double Blind Randomized Controlled Trial, placebo-controlled, multiple countries, preprint, 19 authors, trial NCT04625725 (history) (PROVENT).

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