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0 0.5 1 1.5 2+ Mortality 93% Improvement Relative Risk Death/hospitalization 56% primary Hospitalization 48% Hospitalization/ER 40% SQ vs. IV death 53% SQ vs. IV death/hosp. -71% SQ vs. IV hospitalization -79% SQ vs. IV ER/hosp. 15% Casirivimab/i..  McCreary et al.  LATE TREATMENT Is late treatment with casirivimab/imdevimab beneficial for COVID-19? Prospective study of 2,185 patients in the USA (Jul - Oct 2021) Lower mortality (p=0.009) and death/hosp. (p=0.00031) McCreary et al., medRxiv, December 2021 Favors casirivimab/im.. Favors control

Association of subcutaneous or intravenous route of administration of casirivimab and imdevimab monoclonal antibodies with clinical outcomes in COVID-19

McCreary et al., medRxiv, doi:10.1101/2021.11.30.21266756
Dec 2021  
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Prospective study comparing subcutaneous and intravenous casirivimab/imdevimab, and comparing to a PSM matched control set, showing significantly lower mortality and hospitalization with treatment. Controls were matched with EUA-eligible risk factors only, authors were unable to determine symptom severity.
Efficacy is variant dependent. In Vitro research suggests a lack of efficacy for omicron Liu, Sheward, Tatham, VanBlargan.
risk of death, 93.0% lower, RR 0.07, p = 0.009, treatment 1 of 652 (0.2%), control 29 of 1,304 (2.2%), NNT 48, propensity score matching.
risk of death/hospitalization, 56.0% lower, RR 0.44, p < 0.001, treatment 22 of 652 (3.4%), control 101 of 1,304 (7.7%), NNT 23, propensity score matching, primary outcome.
risk of hospitalization, 48.0% lower, RR 0.52, p = 0.005, treatment 22 of 652 (3.4%), control 85 of 1,304 (6.5%), NNT 32, propensity score matching.
risk of hospitalization/ER, 40.0% lower, RR 0.60, p = 0.003, treatment 40 of 652 (6.1%), control 133 of 1,304 (10.2%), NNT 25, propensity score matching.
SQ vs. IV death, 53.0% lower, RR 0.47, p = 0.52, treatment 1 of 969 (0.1%), control 3 of 1,216 (0.2%), NNT 697, adjusted per study.
SQ vs. IV death/hosp., 71.0% higher, RR 1.71, p = 0.06, treatment 27 of 969 (2.8%), control 21 of 1,216 (1.7%), adjusted per study.
SQ vs. IV hospitalization, 79.0% higher, RR 1.79, p = 0.046, treatment 27 of 969 (2.8%), control 20 of 1,216 (1.6%), adjusted per study.
SQ vs. IV ER/hosp., 15.0% lower, RR 0.85, p = 0.38, treatment 47 of 969 (4.9%), control 71 of 1,216 (5.8%), NNT 101, adjusted per study.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
McCreary et al., 1 Dec 2021, prospective, USA, preprint, 27 authors, study period 14 July, 2021 - 26 October, 2021, average treatment delay 6.0 days.
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This PaperCasirivimab/i..All
Association of subcutaneous or intravenous route of administration of casirivimab and imdevimab monoclonal antibodies with clinical outcomes in COVID-19
PharmD, BCPS, BCIDP Erin K Mccreary, J Ryan Bariola, MD Richard J Wadas, Judith A Shovel, Mary Kay Wisniewski, Michelle Adam, BS Debbie Albin, MS Tami Minnier, MD Mark Schmidhofer, MBA Russell Meyers, MD Oscar C Marroquin, MBA Kevin Collins, PhD William Garrard, Lindsay R Berry, PhD Scott Berry, PhD Amy M Crawford, PhD Anna Mcglothlin, MS Kelsey Linstrum, MS Anna Nakayama, MS Stephanie K Montgomery, MD Graham M Snyder, MD Donald M Yealy, MD MPH Derek C Angus, PhD Paula L Kip, MD MSc Christopher W Seymour, MD MPH David T Huang, PhD Kevin E Kip
Findings: Among 1,956 propensity-matched adults, outpatients who received casirivimab and imdevimab subcutaneously had a 28-day rate of hospitalization or death of 3.4% (n=652) compared to 7.8% (n=1,304) in non-treated controls [risk ratio 0.44 (95% confidence interval: 0.28 to 0.68, p < .001)]. Among 2,185 outpatients who received subcutaneous (n=969) or intravenous (n=1,216) casirivimab and imdevimab, the 28-day rate of hospitalization/death was 2.8% vs. 1.7%, respectively, which resulted in an adjusted risk difference of 1.5% (95% confidence interval: -0.5% to 3.5%, p=.14). The 28-day adjusted risk differences comparing subcutaneous to intravenous route for death, ICU admission, and mechanical ventilation were 0.3% or less, although the 95% confidence intervals were wide. Meaning: Subcutaneously administered casirivimab and imdevimab is associated with reduced hospitalization or death amongst outpatients with mild to moderate COVID-19 compared to no treatment, and has a small, adjusted risk difference compared to patients treated intravenously.
Treated and Nontreated Analysis
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Gov, Uk, Patient information leaflet for Ronapreve
Huang, Mccreary, Bariola, The UPMC OPTIMISE-C19 (OPtimizing Treatment and Impact of Monoclonal antIbodieS through Evaluation for COVID-19) trial: a structured summary of a study protocol for an open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization, Trials, doi:10.1186/s13063-021-05316-3
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Reitz, Seymour, Vates, Strategies to Promote ResiliencY (SPRY): a randomised embedded multifactorial adaptative platform (REMAP) clinical trial protocol to study interventions to improve recovery after surgery in high-risk patients, BMJ Open, doi:10.1136/bmjopen-2020-037690
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Late treatment
is less effective
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