19 augustus 2021: Zie ook dit artikel: https://kanker-actueel.nl/monoklonaal-antilichaam-vir-7831-geeft-85-procent-minder-ziekenhuisopnames-of-overlijden-bij-patienten-met-het-coronavirus-covid-19-in-vroeg-stadium-in-vergelijking-met-placebo.html

19 augustus 2021: Bron: Universiteit van Oxfort

De Randomized Evaluation of COVID-19 Therapy (RECOVERY)-studie heeft aangetoond dat de combinatie van 2 monoklonale middelen, casirivimab en imdevimab, ook wel REGEN-COV genoemd, het risico op overlijden vermindert wanneer het wordt toegediend aan patiënten die in het ziekenhuis zijn opgenomen met ernstige COVID-19 en die zelf daarvoor geen natuurlijke antilichaamrespons - antistoffen tegen het coronavirus hebben ontwikkeld.

Eerdere onderzoeken bij niet in het ziekenhuis opgenomen COVID-19-patiënten hebben aangetoond dat de behandeling de virale belasting vermindert, de tijd tot het verdwijnen van symptomen verkort en het risico op ziekenhuisopname of overlijden aanzienlijk vermindert. RECOVERY is de eerste studie die groot genoeg is om definitief te bepalen of deze behandeling de mortaliteit vermindert bij patiënten die in het ziekenhuis zijn opgenomen met ernstige COVID-19.

Tussen 18 september 2020 en 22 mei 2021 werden 9785 patiënten die in het ziekenhuis waren opgenomen met COVID-19 willekeurig toegewezen aan de gebruikelijke zorg plus de antilichaamcombinatiebehandeling (casirivimab 4g met imdevimab 4g via intraveneuze infusie) of alleen gebruikelijke zorg als onderdeel van de RECOVERY-studie.

Hiervan was ongeveer een derde seronegatief bij baseline (dwz ze hadden zelf geen antistoffen ontwikkeld), de helft was seropositief (dwz ze hadden al wel antistoffen ontwikkeld) en een zesde had een onbekende serostatus.

Onder patiënten die alleen de gebruikelijke zorg kregen, was de mortaliteit na 28 dagen tweemaal zo hoog bij degenen die seronegatief waren (30%) vs. degenen die seropositief waren (15%) bij deelname aan het onderzoek


Alle verdere details van de studie zijn te vinden in dit artikel van de universiteit van Oxfort: 

RECOVERY trial Regeneron’s monoclonal antibody combination reduces deaths for hospitalised COVID-19 patients

The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial has demonstrated that the investigational antibody combination developed by Regeneron reduces the risk of death when given to patients hospitalised with severe COVID-19 who have not mounted a natural antibody response of their own.

Between 18 September 2020 and 22 May 2021, 9785 patients hospitalised with COVID-19 were randomly allocated to receive usual care plus the antibody combination treatment (casirivimab 4g with imdevimab 4g by intravenous infusion) or usual care alone as part of the RECOVERY trial. Of these, about one-third were seronegative at baseline (ie they had not mounted a natural antibody response of their own), one-half were seropositive (ie they had already developed natural antibodies), and one-sixth had unknown serostatus. Among patients who received usual care alone, 28-day mortality was twice as high in those who were seronegative (30%) vs. those who were seropositive (15%) at study entry. Follow-up is complete for 99% of participants and preliminary results are announced today.

Among patients who were seronegative at baseline (the primary analysis population for this comparison), the antibody combination significantly reduced the primary outcome of 28-day mortality by one-fifth compared with usual care alone (24% of patients in the antibody combination group died vs 30% of patients in the usual care group; rate ratio 0·80; 95% confidence interval 0·70–0·91; p=0·001). Thus, for every 100 such patients treated with the antibody combination, there would be six fewer deaths.

There was clear evidence that the effect of treatment in seronegative patients differed from that in seropositive patients (test for heterogeneity p=0·001). When combining the larger seropositive group (as well as those with unknown status) with the seronegative patients, there was no longer a significant effect on 28-day mortality (overall 20% of patients in the antibody combination group died vs 21% of patients in the usual care group; rate ratio 0·96; 95% confidence interval 0·86–1·03; p=0·17).

For the seronegative patients, the duration of hospital stay was four days shorter (median 13 days vs. 17 days) among those allocated to the antibody combination than the usual care group, and the proportion of patients discharged alive by day 28 was greater (64% vs. 58%; rate ratio 1·19, 95% confidence interval 1·08 to 1·30). Among the seronegative patients not on invasive mechanical ventilation at baseline, the risk of progressing to the composite endpoint of invasive mechanical ventilation or death was lower among those allocated to the antibody combination than the usual care group (30% vs. 37%; risk ratio 0·83, 95% confidence interval 0·75 to 0·92). No such benefits were seen in the overall study population (combining patients with negative, positive, or unknown serostatus).

Originele publicatie die nog niet peer reviewed is staat hier: 

Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial


RECOVERY Collaborative GroupPeter W HorbyMarion MafhamLeon PetoMark CampbellGuilherme Pessoa-AmorimEnti SpataNatalie StaplinJonathan R EmbersonBenjamin PrudonPaul HineThomas BrownChristopher A GreenRahuldeb SarkarPurav DesaiBryan YatesTom BewickSimon TiberiTim FeltonJ Kenneth BaillieMaya H BuchLucy C ChappellJeremy N DaySaul N FaustThomas JakiKatie JefferyEdmund JuszczakWei Shen LimAlan MontgomeryAndrew MumfordKathryn RowanGuy ThwaitesDavid M WeinreichRichard HaynesMartin J Landray

SUMMARY

Background REGEN-COV is a combination of 2 monoclonal antibodies (casirivimab and imdevimab) that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike protein. We aimed to evaluate the efficacy and safety of REGEN-COV in patients admitted to hospital with COVID-19.

Methods In this randomised, controlled, open-label platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Eligible and consenting patients were randomly allocated (1:1) to either usual standard of care alone (usual care group) or usual care plus a single dose of REGEN-COV 8g (casirivimab 4g and imdevimab 4g) by intravenous infusion (REGEN-COV group). The primary outcome was 28-day mortality assessed first among patients without detectable antibodies to SARS-CoV-2 at randomisation (seronegative) and then in the overall population. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936).

Findings Between 18 September 2020 and 22 May 2021, 9785 patients were randomly allocated to receive usual care plus REGEN-COV or usual care alone, including 3153 (32%) seronegative patients, 5272 (54%) seropositive patients and 1360 (14%) patients with unknown baseline antibody status. In the primary efficacy population of seronegative patients, 396 (24%) of 1633 patients allocated to REGEN-COV and 451 (30%) of 1520 patients allocated to usual care died within 28 days (rate ratio 0·80; 95% CI 0·70-0·91; p=0·0010). In an analysis involving all randomised patients (regardless of baseline antibody status), 944 (20%) of 4839 patients allocated to REGEN-COV and 1026 (21%) of 4946 patients allocated to usual care died within 28 days (rate ratio 0·94; 95% CI 0·86-1·03; p=0·17). The proportional effect of REGEN-COV on mortality differed significantly between seropositive and seronegative patients (p value for heterogeneity = 0·001).

Interpretation In patients hospitalised with COVID-19, the monoclonal antibody combination of casirivimab and imdevimab (REGEN-COV) reduced 28-day mortality among patients who were seronegative at baseline.

Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).

Competing Interest Statement

David M Weinreich is Senior Vice President, Global Clinical Development, Regeneron Pharmaceuticals Inc. and holds stock/stock options in Regeneron Pharmaceuticals. No other authors have competing interests.

Clinical Trial

The trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936).

Clinical Protocols

https://www.recoverytrial.net

Funding Statement

UK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056). Casirivimab/imdevimab (REGEN-COV2) was provided free of charge by Regeneron Pharmaceuticals Inc.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The trial is conducted in accordance with the principles of the International Conference on Harmonisation-Good Clinical Practice guidelines and approved by the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the Cambridge East Research Ethics Committee (ref: 20/EE/0101).

All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

Footnotes

  • * The writing committee and trial steering committee are listed at the end of this manuscript and a complete list of collaborators in the Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial is provided in the Supplementary Appendix.

Paper in collection COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv


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