There are now hundreds of papers on COVID-19 and multiple sclerosis and it has become boring for most people, but we need to keep an eye out for what the current information is showing, as it may help you or your neuro choose what you are going to do next.
The World of MS got together to share their information because with larger numbers, clarity appeared. Early glimpses was based on about 2,000 confirmed or suspected cases Simpson-Yap et al. Neurology. 2021;97:e1870-e1885. This suggested that “rituximab/ocrelizumab use may be a risk factor for more severe COVID-19”
We have moved on and now there are about five and a half thousand cases, so about double the original number reprted previously. So besides the effects of features affecting the general population we continue to see that progressive MS, and higher disability are associated with more severe COVID-19. The conclusions are the same the study “confirms that the use of anti-CD20 medication (both ocrelizumab and rituximab),……………..are associated with more severe course of COVID-19”.
In the orginal study they compared the other drugs to dimethyl fumarate but in this new study they compare to glatiramer acetate and concluded that ocelizumab and rituximab increased the risk of hospitalizationby 4-7% (see below), which seems a small increase compared to doubling risk for rituximab based on the odds ratio reported previously.
But in the original study there was a small increased (albeit non-significant) risk of hospitalization with glatiramer acetate compared to dimethyl fumarate. So let’s try and look at the same data and doing some calculations on the back of an envelope, so there seems to be a doubling of hospitalisation risk with anti-CD20 depleting antibodies compared to dimethyl fumarate, maybe be looking worse for occrelizumab than before, but in reality for this outcome rituximab and ocrelizumab look about the same. It would be hard to see why rituximab should be worse than ocrelizumab in this respect from a biological point of view
Data from suspected and confirmed cases (Table 2 covid cases/total Simpson Yap et al. 2021 and etable 6 covid cases Simpson Yap et al. 2021)
So isn’t it interesting the way you describe and percieve risk. Here I suspect the view is to down play the risk, as we sense that the risk is low and we don’t want to alarm people. So maybe they should change how we describe genetic risk as we often hear of doubling risk but 1 cases in 10,000,000 people does not seem that much different to 2 in 10,000,000. You worry if you have the gene in the first scenario but not the in the second scenario. I suspect the media would not be interested in a lot of genetic/epidemiology papers if the second way of reporting was the norm.
Interestingly fingolimod did not show increased risk of hospitalization compared to dimethyl fumarate (or glatiramer acetate for that matter) and was a 3-4 times reduced risk of hospitalization compared to anti-CD20 antibodies. Now remember that both fingolimod and the anti-CD20 depleting antibodies inhibit COVID-19 vaccinate iduced antibody responses and there is a peripheral T cell response after CD20-treatment but not fingolimod treatment.
How could that be in anti-CD20 has higher COVID-19 riskes than fingolimod?
Have a read of this preprint
Baker D, Forte E, Pryce G, Kang AS, James LJ, Giovannoni G, Schmierer K. The impact of sphinogosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination. Available at SSRN: https://ssrn.com/abstract=4200732.
Simpson-Yap S, Pirmani A, Kalincik T, De Brouwer E, Geys L, Parciak T, Helme A, Rijke N, Hillert JA, Moreau Y, Edan G, Sharmin S, Spelman T, McBurney R, Schmidt H, Bergmann AB, Braune S, Stahmann A, Middleton RM, Salter A, Bebo B, Van der Walt A, Butzkueven H, Ozakbas S, Boz C, Karabudak R, Alroughani R, Rojas JI, van der Mei IA, Sciascia do Olival G, Magyari M, Alonso RN, Nicholas RS, Chertcoff AS, de Torres AZ, Arrambide G, Nag N, Descamps A, Costers L, Dobson R, Miller A, Rodrigues P, Prčkovska V, Comi G, Peeters LM. Updated Results of the COVID-19 in MS Global Data Sharing Initiative: Anti-CD20 and Other Risk Factors Associated With COVID-19 Severity. Neurol Neuroimmunol Neuroinflamm. 2022 Aug 29;9(6):e200021. doi: 10.1212/NXI.0000000000200021.
Background and objectives: Certain demographic and clinical characteristics, including the use of some disease-modifying therapies (DMTs), are associated with severe acute respiratory syndrome coronavirus 2 infection severity in people with multiple sclerosis (MS). Comprehensive exploration of these relationships in large international samples is needed.
Methods: Clinician-reported demographic/clinical data from 27 countries were aggregated into a data set of 5,648 patients with suspected/confirmed coronavirus disease 2019 (COVID-19). COVID-19 severity outcomes (hospitalization, admission to intensive care unit [ICU], requiring artificial ventilation, and death) were assessed using multilevel mixed-effects ordered probit and logistic regression, adjusted for age, sex, disability, and MS phenotype. DMTs were individually compared with glatiramer acetate, and anti-CD20 DMTs with pooled other DMTs and with natalizumab.
Results: Of 5,648 patients, 922 (16.6%) with suspected and 4,646 (83.4%) with confirmed COVID-19 were included. Male sex, older age, progressive MS, and higher disability were associated with more severe COVID-19. Compared with glatiramer acetate, ocrelizumab and rituximab were associated with higher probabilities of hospitalization (4% [95% CI 1-7] and 7% [95% CI 4-11]), ICU/artificial ventilation (2% [95% CI 0-4] and 4% [95% CI 2-6]), and death (1% [95% CI 0-2] and 2% [95% CI 1-4]) (predicted marginal effects). Untreated patients had 5% (95% CI 2-8), 3% (95% CI 1-5), and 1% (95% CI 0-3) higher probabilities of the 3 respective levels of COVID-19 severity than glatiramer acetate. Compared with pooled other DMTs and with natalizumab, the associations of ocrelizumab and rituximab with COVID-19 severity were also more pronounced. All associations persisted/enhanced on restriction to confirmed COVID-19.
Discussion: Analyzing the largest international real-world data set of people with MS with suspected/confirmed COVID-19 confirms that the use of anti-CD20 medication (both ocrelizumab and rituximab), as well as male sex, older age, progressive MS, and higher disability are associated with more severe course of COVID-19.
COI: Dr Ruth (Barts MS) is an author. The UK input seems to have reduced from the total data that is dominated by responses from Sweden and North America
Disclaimer. These are the views of the Author
