#MSCOVID19 consortia reporting increased risks of more severe disease from ocrelizumab and rituximab

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The product of success is a healthy bank balance for the manufacturers of anti-CD20 antibodies, but it also means you get the bad news when it comes to the consequence of COVID 19 infections, because you have the data. Anti-CD20 increases your risk of more severe COVID-19.

In this study which is the largest reported we have data from 657 (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19. Obviously this can’t say if it increases your risk of infection but it makes the suggestion that if you do get infected the risks for hospitalisation and intensive care are increased if you are untreated or treated with an anti-CD-20 such as ocrelizumab and rituximab.

In the study there were 515 untreated people, 474 people treated with dimethyl fumarate, 343 people treated with fingolimod, 385 people treated with natalizumab but a whopping 836 people treated with ocrelizumab and 400 people treated with rituximab. However only 56 people with alemtuzumab and 46 people treated with cladribine. This does not mean because there are more ocrelizumab COVID cases it puts you at risk of COVID, but it says ocrelizumab is a a popular treatment. Rituximab is heavily used in Sweden and they contributed 290 people to the study. The UK provided 131 and in the USA there were 1,161

It was clear that the risk factors like age, sex and co-morbidities were risk factors for hosptialisaztion, but also if you were progressive and had more disability. As some of these factors go hand in hand the data was adjusted to allow for this but still people on ocrelizumab were about twice as likely to be hosptialised compared to other DMT 1.75 (1.29-2.38) and this is supported by the finding with rituximab adjusted Odds ratio 2.43 (95% confidence limits 1.87-2.95) and about three (Ocrelizumab aOR 3.08 (1.83-5.17) to five (rituximab OR 4.69(2.49-8.83) more likely to be admited to the ICU but no influence on death.

Risk of hosptialization compared to dimethyl fumarate = 1.00. If you are above one you have more risk. The lines are for confirmed and suscpected (dashed) COVID-19 cases. If the line crosses one there is no difference but if completely above there is 95% chance that this is going to make you worst if affected.

Risk of intensive care admission compared to dimethyl fumarate = 1.00. If you are above one you have more risk. The lines are for confirmed and suscpected (dashed) COVID-19 cases. If the line crosses one there is no difference but if completely above there is 95% chance that this is going to make you worst if affected. As you can see here ocrelizumab is no worse but rituximab is still problematic. Alemtuzumab has a wide confidence interval so some people may have suffered but I suspect there are not enough points of information to be sure.

The confidence intervals for the risks for cladribine and alemtuzumab are large but they cross one and so are no more likely to be hospitalised than with dimethyl fumarate. If you had 500 people in these groups you would be more certain what happens. The other risk factor for severe covid-19 was not being treated so ensure you get vaccinated.

Associations of DMT therapies with COVID-19 severity in multiple sclerosisSteve Simpson-Yap, Edward De Brouwer, Tomas Kalincik, Nick Rijke, Jan Hillert, Clare Walton, Gilles Edan, Yves Moreau, Tim Spelman, Lotte Geys, Tina Parciak, Clément Gautrais, Nikola Lazovski, Ashkan Pirmani, Amin Ardeshirdavani, Lars Forsberg, Anna Glaser, Robert McBurney, Hollie Schmidt, Arnfin Bergmann, Stefan Braune, Alexander Stahmann, Rodden Middleton, Amber Salter, Robert J. Fox, Anneke van der Walt, Helmut Butzkueven, Raed Al-Roughani, Serkan Ozakbas, Juan I Rojas, Ingrid van der Mei, Nupur Nag, Rumen Ivanov, Guilherme Sciascia do Olival, Alice Estavo Dias, Melinda Magyari, Doralina Guimarães Brum, Maria Fernanda Mendes, Ricardo Alonso, Richard Nicholas, Johana Bauer, Anibal Chertcoff, Ana Zabalza, Georgina Arrambide, Alexander Fidao, Giancarlo Comi, Liesbet M. PeetersmedRxiv 2021.02.08.21251316; doi: https://doi.org/10.1101/2021.02.08.21251316 

Background People with multiple sclerosis (MS) are a vulnerable group for severe COVID-19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS.

Methods Data from 12 data-sources in 28 countries were aggregated. Demographic and clinical covariates were queried, alongside COVID-19 clinical severity outcomes, hospitalisation, admission to ICU, requiring artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression.

Results 657 (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analysed. Older age, progressive MS-phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.56,95%CI=1.01-2.41; aOR=2.43,95%CI=1.48-4.02) and ICU admission (aOR=2.30,95%CI=0.98-5.39; aOR=3.93,95%CI=1.56-9.89), though only rituximab was associated with higher risk of artificial ventilation (aOR=4.00,95%CI=1.54-10.39). Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.75,95%CI=1.29-2.38; aOR=2.76,95%CI=1.87-4.07) and ICU admission (aOR=2.55,95%CI=1.49-4.36; aOR=4.32,95%CI=2.27-8.23) but only rituximab with artificial ventilation (aOR=6.15,95%CI=3.09-12.27). Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.86,95%CI=1.13-3.07; aOR=2.88,95%CI=1.68-4.92) and ICU admission (aOR=2.13,95%CI=0.85-5.35; aOR=3.23,95%CI=1.17-8.91), but only rituximab with ventilation (aOR=5.52,95%CI=1.71-17.84). Importantly, associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death.

Conclusions Using the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalisation, ICU admission, and requiring artificial ventilation, and ocrelizumab with hospitalisation and ICU admission, suggesting their use may be a risk factor for more severe COVID-19.

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MouseDoctor

5 comments

Leave a Reply to Anonymous Cancel reply

    • Yes I think it tells us that the data is not that firm as you would not expect rituximab to be worse and the truths is going to be somewhere in between.

  • This seems like it might be a case of looking at the data and then deciding how to draw the curve.

    For instance, why would you normalize to Dimethyl Fumarate ?
    Why not on the untreated ?

    It would make the interpretation look different for sure.
    Are some MS drugs prophylactic ?
    Maybe the OR is not as bad for some of the sledgehammer drugs ?

    Maybe all of this blended data from different countries does not adequately decouple the regional differences in severity of disease course in the population and the percentage of people on the DMT also has a regional bias that affects the overall statistics.

    It is an interesting study, but I would not panic if I was on a DMT that was working and with higher OR.

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