Looks like Prophylactic SARS-CoV-2 antibodies work…Protection against COVID-19 for the immunosuppressed?

L

This would need to be approved first

ProfAngry said many months ago that perhaps the best use of an anti-SAR-COV-2 antibodies was to prevent COVID-19 is people at risk to COVID-19. This would especially be the case for someone that has made no anti-vaccine response like fingolimod or ocrelizumab. However the licenced dose is 600mg and not 1200mg (see below) but things are changing with options for people without a protetive anti-SARS CoV 2 response.

There is likely to be of benefit

Izza et al. MedrXiv 2021. https://doi.org/10.1101/2021.11.10.21265889

Background: Data show that a single dose of casirivimab and imdevimab (REGEN-COV®) is effective in treating hospitalized individuals and outpatients with COVID-19 and in post-exposure prophylaxis. We present results from a phase 1, double-blind, placebo-controlled trial evaluating the safety, tolerability, and efficacy of repeat monthly doses of subcutaneous (SC) REGEN-COV in uninfected adult volunteers who were healthy or had chronic stable medical conditions. Methods: Subjects were randomized (3:1) to SC REGEN-COV 1200 mg or placebo dosed every 4 weeks for up to 6 doses. The primary and secondary endpoints evaluated the safety, pharmacokinetics, and immunogenicity of multiple-dose administration of REGEN-COV. Efficacy was evaluated by the incidence of COVID-19 or SARS-CoV-2 seroconversion. Results: In total, 969 subjects were treated. Repeat monthly dosing of SC REGEN-COV led to a 92.4% relative risk reduction in clinically-defined COVID-19 compared to placebo (3/729 [0.4%] vs 13/240 [5.4%]; odds ratio: 0.07 [95% CI, 0.01–0.27]), and a 100% reduction in laboratory-confirmed COVID-19 (0/729 vs 10/240 [4.2%]; odds ratio 0.00). Development of anti-drug antibodies was low (<5% subjects). No grade ≥3 injection-site reactions (ISRs) or hypersensitivity reactions were reported. A slightly higher percentage of subjects reported TEAEs with REGEN-COV (54.9%) than placebo (48.3%), due to ISRs (all grade 1-2). Serious adverse events were rare and occurred at similar percentages in the REGEN-COV and placebo groups. No deaths were reported in the 6-month treatment period. Conclusions: Repeated monthly administration of 1200 mg SC REGEN-COV was well-tolerated with low immunogenicity, and showed a substantial risk reduction in COVID-19 occurrence. (ClinicalTrials.gov identifier, NCT04519437)

The information below is extracted from

https://www.england.nhs.uk/coronavirus/publication/casirivimab-and-imdevimab-for-patients-hospitalised-due-to-covid-19/

Exprected from the Interim Clinical Commissioning Policy: Casirivimab and imdevimab for patients hospitalised due to COVID-19 Ovember 4 2021

In the UK

Casirivimab and imdevimab is recommended to be available as a treatment
option for COVID-19 through routine commissioning for hospitalised adults and children
(aged 12 years and above)

1) Patients hospitalised for acute COVID-19 illness: to be treated at the off-label dose of
2.4g

2) Patients with hospital-onset COVID-19: to be treated at a dose of 1.2g, in line with the
conditional marketing authorisation

Eligibility criteria
Patients must meet all of the eligibility criteria and none of the exclusion criteria under one of
the following pathways3 4
:
1) Patients hospitalised with acute COVID-19
Hospitalised patients are eligible to be considered for casirivimab and imdevimab if:
• SARS-CoV-2 infection is confirmed or where
a multidisciplinary team (MDT) has a high level of confidence that the clinical and/or
radiological features suggest that COVID-19 is the most likely diagnosis

AND
• Hospitalised specifically for the management of acute symptoms of COVID-19

AND
Negative for baseline serum anti-spike (anti-S) antibodies against SARS-CoV-2

There are also criteria for Patients with hospital-onset COVID-19

Exclusion criteria
The following patients are not eligible for treatment:
• Children weighing less than 40kg
• Children aged under 12 years
• Known hypersensitivity reaction to the active substances or to any of the excipients of
casirivimab and imdevimab listed in the Summary of Product Characteristics (SmPC)
• Previously received treatment in hospital with casirivimab and imdevimab at the 2.4g
(combined) dose or higher during this course of infection

Serum antibody status
Patients may be tested for anti-S1 or anti-S2 antibodies using any validated quantitative or
qualitative anti-S assay that measures either IgG or total antibody levels. Serostatus should
be established in line with the pre-determined thresholds relevant to the assay being used by
the testing laboratory. Quantitative assays with pre-specified thresholds for seropositivity
should return clear binary (i.e. either ‘negative’ or ‘positive’) results based on these
thresholds. For quantitative assays without a formal threshold for serostatus, clinical
decision-making should guide treatment decisions.

In immunocompromised groups, very low ‘positive’ levels of anti-S antibody on a quantitative
assay (within the bottom 10% of the assay’s positive range) should be interpreted in the
context of clinical decision-making and laboratory advice and a decision to treat may still be
made by the MDT on a case-by-case basis.

Providers will be required to report anti-S antibody levels in treated patients, and the corresponding reference range of the local assay, for central monitoring.

In immunodeficient patients on replacement immunoglobulin (intravenous or subcutaneous),
the positive detection of anti-S antibodies should be regarded as a ‘positive of unknown
significance’. Patients on replacement immunoglobulin testing positive only for anti-S (and
negative for anti-N antibodies) should therefore be considered to be seronegative for SARSCoV-2, and MDT assessment should judge their eligibility for nMAB treatment.

Should evidence for passive transmission of anti-N antibodies through replacement immunoglobulin
emerge in the future, the detection of anti-N antibodies should also be regarded as a
‘positive of unknown significance’.

Therefore if you are on a DMT of concern it would help if you knew your serological status, i.e. positivity to the COVID-19 vaccines or past infection

If there are concerns or questions around laboratory sensitivity or cut-offs these should be
discussed in the first instance with local laboratory leads who will have access to
comparative and performance data from the EQA scheme participation

Summary or medical product characteritistics (SmPC) can be found here.

Pregnancy and women of childbearing potential
The RECOVERY trial included women who were pregnant or breastfeeding, and no serious
adverse events were reported see the SmPC for details

Therefore if you are on a DMT it would be handy to know your vaccination (remembering that antibody levels wane with time but if you were negative at the start you are likely to negative months later.

See DoctorRuths Study. COVID-19 Vaccine Response in People with Multiple Sclerosis

https://doi.org/10.1002/ana.26251

About the author

MouseDoctor

1 comment

  • How likely would NHS approve this treatment for immunosuppressed? Are most pwMS ummunosuppressed enough as per regulatory people’s point of view?

    I feel unlikely this will be offered to the majority of pwMS.

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