#MSCOVID19 Whilst two swallows may make a summer…but it seems two COVID-19 papers make a bummer….for anti-CD20 therapy

Council removes Banksy artwork after complaints of racism | Art and design  | The Guardian
Banksy and the Swallow

bummer = a disappointing or unpleasant situation or experience.

When it all started the Great and the Good (Neuro) experts looked at the different DMT and thought about the risks

Disease-Modifying Therapies During the COVID-19 Outbreak: A Narrative Review of International and National Recommendations Smathorn et al.  International Journal of MS Care (2020) 22 (4): 151–157.https://doi.org/10.7224/1537-2073.2020-037

“There is significant agreement among most experts’ recommendations from a variety of sources based on collective clinical experience. However, the recommendations will likely evolve because sufficient clinical data are limited. Several ongoing registries will help provide information for future recommendations”.

They predicted the highly active DMT would make things worse. Luckily the the data suggests this view was not quite right

In France the data came in that there was not much of an impact, but the larger talian data set has surfaced as a pre print and they..Somarni et al. Disease Modifying Therapies and COVID-19 Severity in Multiple sclerosis SSRN http://dx.doi.org/10.2139/ssrn.3631244 said CD20 depleting antibodies (Ocrelizumab) increase the risk of developing COVID-19 by 1.84 (95%CI 1.31-2.56) times. So that is one swallow. So now a new study from Iran

Sahraian MA et al. Evaluation of the rate of COVID-19 infection, hospitalization and death among Iranian patients with multiple sclerosis Mult scler Rel Disord. https://doi.org/10.1016/j.msard.2020.102472

CD20-depleting antibody (Rituximab) was associated with increase rate of COVID-19 infection but not with hospitalization rate. The risk of developing COVID19 was 1.85 (95% CI 1.37-2.33). So the second Swallow or is this the third because another study from Iran, examining other patients reported the same thing.

Safavi F et al B-cell depleting therapies may affect susceptibility to acute respiratory illness among patients with multiple sclerosis during the early COVID-19 epidemic in Iran. Mult Scler Relat Disord. 2020;43:102195. Again it was shown that rituximab increase the risk of COVID-19 with an Odds ratio 1.59.

Then maybe a forth swallow as the Swedish experience research.org/2020/05/mscovid19-swedish-experience suggests odds ratio of 1.73. I suspect before we know it, it will be a flock

The Swallows have arrived

Late breaking Nws at ACTRIMS

SS02.04 – First results of the COVID-19 in MS Global Data Sharing Initiative suggest anti-CD20 DMTs are associated with worse COVID-19 outcomes

Presentation NumberSS02.04Presentation TopicCOVID-19Lecture Time11:21 – 11:33

What is the biology behind this B cells and risk?

CD20 therapies (rituximab, ocrelizumab, ofatumumab etc) maintain your B cells at a low level.

It is now known that (a) B cell depletion can inhibit the generation of B cell responses to vaccines and (b) in some cases inhibit the B cell responses to SARS-CoV-2

(c) Cross reactive immunity to cold causing cornoviruses provide protection against SARS-CoV-2.

CD20-depletion could stop these responses

Alternatively (d) B cell depletion causes hypogammaglobulinaemia (loss of antibodies) in some people. This can be associated with (e) loss of vaccine responses.

Therefore immunity to cold-coronavirus may be lost, exposing one to symptomatic COVID-19

THis could a increase your risk of not being able to defend against the first few viral particles and so increase your viral load allowing you to be come infected in the first place or becoming symptomatic once you are infected.

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  • It’s interesting to note the uncertainty that persists, both in terms of different conclusions reached by differing ‘authorities’ and the choice of words, ‘MAY increase’.

    • May is a scientifici training you never say “does” but when the recommendations were made the idea was based on immune suppression. I think natalizumab was the interesting one as they alll said OK but inflammed lung upregulates VCAM-1 and monocyctes express CD49d/VLA-4. In the italian data it is significant P=0.02

  • Thanks for your work! It’s so helfpul!

    I had my last dose Ocrevus last month (the fifth overall). I asked the immunologist about my B cell level. He said is generally not lowered. What does that mean? That Ocrevus does not work? Or that there are people who has no strongly lowered level but Ocrevus works anyway?

    • If your B cells count is not lowered you have to ask is the antibody working, however you also have to ask when were the bloods taken. As we have shown your memory B cells can be be depleted for longer than your total CD19 population but I would urge everyone taking a depleting treatment to ensure that their depleting antibody is doing what it is supposed to do. If it stops depleting you may have anti-drug antibodies

      • Is it known that people with Ocrevus/ Rituximab develop anti-drug antibodies? Never heard that in terms of Ocrevus.

        Blood was taken before Infusion, 6 months after last dose.

        • Never heard of that with ocrevus is because the manufacturers have convinced the world tha they don’t exist…FDA website “The incidence of immunogenicity was approximately 1%. Out of 1311 patients treated with ocrelizumab, 12 (~1%) tested positive for treatmentemergent ADAs, of which 2 patients tested positive for neutralizing
          antibodies. Patients with neutralizing antibodies showed faster clearance of ocrelizumab and faster B-cell repletion in 2 patients. There was no impact
          on safety and efficacy in all the patients with of treatment-emergent ADAs”…..Really give it time

          Never heard of that with rituximab…you are not reading enough

          6.4 Immunogenicity
          As with all therapeutic proteins, there is a potential for immunogenicity. The observed incidence of antibody (including neutralizing antibody) positivity in an assay is highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Rituxan with the incidence of antibodies to other products may be

          Using an ELISA assay, anti-human anti-chimeric antibody (HACA)…..A total of 273/2578 (11%) patients with RA tested positive for HACA at any time after receiving
          Rituxan. HACA positivity was not associated with increased infusion reactions or other adverse reactions. Upon further treatment, the proportions of patients with infusion reactions were similar between HACA positive and negative patients, and most reactions were mild to moderate. Four
          HACA positive patients had serious infusion reactions, and the temporal relationship between
          HACA positivity and infusion reaction was variable.

          A total of 23/99 (23%) Rituxan-treated patients with GPA and MPA tested positive for HACA by
          18 months. The clinical relevance of HACA formation in Rituxan-treated patients is unclear.

          Blood was taken 6 months after last dose is when B cells have repopulated and is nothing to worry about, about 5% of people will be back to normal CD18 levels by 6 months…maybe good news you could sneak in a COVID vaccination before infusion and you may have enough cells to make a decent antibody response.

  • Hi MD – as usual just checking in with any new anti CD20 data to check

    – does it affect mortality from Covid-19?
    – are we still looking at older, co-morbid more progressive patients for the highest risk?
    – is it worse in people who have been on for longer as Prof G recently suggested?

    Thanks for bringing us up to date as usual!

  • What is meant by “ WORSE COVID-19 OUTCOMES”. I understand the increased chances (2x) of catching COVID and
    being symptomatic…Is that the “outcome” being referred to here or are they referring to increased chance of severe disease course, hospitalization and death?

    • Most people that catch SARS-COV-2 are asymptomatic, This may be 50-80% of people. So a subtle change in immunity may increase the viral load abit to make you get that cough/fever etc. In these cases it is the rik of being symptomatic, there may be a small but higher chance of hospitalisation.

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