MSCOVID19. Anti-CD20 more mud coming your way and its deadly mud.

M

Anti-CD20 has been the go to drug in MS in recent years. Cladribine works in a similar way but has be tarred by its past and mud slung to suggest a cancer link during the trials, which was later shown to be chance, has stuck in the minds of neuros. The cancer risk was less than found in the early ocrelizumab trials but the mud didn’t stick there because it was countered.

The mud for anti-CD20 is called COVID-19. Anti-CD20 drugs have taken abit of a kicking when it comes to news in COVID-19, it blunted vaccine responses and influences COVID-19 severity. This view is countered, but like an elastic band it keeps bouncing back over and over again. So here is another one from the USA. So as COVID-19 is not going away anytime some would this influence your choice?

COVID-19 Outcomes Among Users of CD20 Inhibitors for Immune-Mediated Diseases: A Comparative Cohort StudyPatel, N. J., D’Silva, K. M., Hsu, T. Y.- T., DiIorio, M. A., Fu, X., Cook, C. E., Prisco, L. C., Martin, L. W., Vanni, K. M. M., Zaccardelli, A., Zhang, Y., Sparks, J. A., Wallace, Z. S.MedRXiv 10.1101/2021.08.05.21261643 

Objective: Patients with immune-mediated diseases treated with CD20 inhibitors may have worse COVID-19 outcomes due to impaired humoral immunity, but differences versus the general population are unknown.

Methods: We identified patients with immune-mediated diseases who received CD20 inhibitors within one year prior to the index date of PCR-confirmed COVID-19 between January 31, 2020, and January 31, 2021. Comparators with COVID-19 were matched up to 5:1 by age, sex, and PCR date. Hazard ratios (HRs) and 95% confidence intervals (CIs) for hospitalization, mechanical ventilation, and death in CD20 inhibitor users versus comparators were estimated using Cox regression.

Results: We identified 114 cases with COVID-19 who had received CD20 inhibitors for immune-mediated diseases (mean age 55 years, 70% female) and 559 matched comparators with COVID-19 (mean age 54 years, 70% female). CD20 inhibitor-treated cases had higher mortality (aHR 2.16; 95% CI: 1.03 to 4.54) than matched comparators. Risks of hospitalization (aHR 0.88; 95% CI: 0.62 to 1.26) and mechanical ventilation (aHR 0.82; 95% CI: 0.36 to 1.87) were similar. Similar trends were seen in analyses according to type of indication (e.g., rheumatic or neurologic disease) and duration of CD20 inhibitor use (<1 or ≥1 year), and after excluding patients with interstitial lung disease, cancer, and those on glucocorticoids prior to COVID-19 diagnosis. Conclusions: Patients who received CD20 inhibitors for immune-mediated diseases prior to COVID-19 had higher mortality following COVID-19 than matched comparators, highlighting the urgent need to mitigate excess risks in CD20 inhibitor users during the ongoing pandemic.

Among the immune-mediated disease patients who received a CD20 inhibitor, 90 (79%) received rituximab and 26 (23%) received ocrelizumab; two patients had received rituximab initially but were later switched to ocrelizumab (Table 2). The most common indication for CD20 inhibitor use was rheumatic disease (54 [47%]), followed by neurologic conditions (43 [38%]) (Table 2). The duration of CD20 inhibitor use was <1 year in 33 (29%) patients, 1-3 years in 51 (45%), and >3 years in 30 (26%).

Now this is disturbing as it implies CD20 antibodies impact on life, but I must say that we need to carefully control this as people with disability and comrobidities are more likely to use anti CD20 as it is licenced for progressive MS and they may have more risk factors for a bad time. Other studies and a number of other studies have not supported this. If we look at another preprint it says this

Simpson Yap et al. Associations of DMT therapies with COVID-19 severity in multiple sclerosis doi: https://doi.org/10.1101/2021.02.08.21251316

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), No associations were observed between DMTs and death.

There were over 700 people taking anti-CD20. However, I wonder who every happened to this paper?

I suspect it was binned by the journals it was submitted to and now I think some of the cortributors have published their own cohorts and gone their separate ways.

But rather than one piece of mud, it will be a volley of mud trickling away

Salter A, Fox RJ, Newsome SD, et al. Outcomes and risk factors associated with SARS‐CoV‐2 infection in a North American registry of patients with multiple sclerosis. JAMA Neurol. 2021;e210688.

Spelman T, Forsberg L, McKay K, Glaser A, Hillert J. Increased rate of hospitalisation for COVID-19 among rituximab-treated multiple sclerosis patients: A study of the Swedish multiple sclerosis registry. Mult Scler. 2021 Jul 2:13524585211026272. doi: 10.1177/13524585211026272.

However it does suggest that the work by Patel may not make it.

What are they doing in Sweden?

Landtblom AM, Berntsson SG, Boström I, Iacobaeus E. Multiple sclerosis and COVID-19: The Swedish experience. Acta Neurol Scand. 2021 Sep;144(3):229-235. doi: 10.1111/ane.13453.

About the author

MouseDoctor

3 comments

  • Thank you for this, and all the other posts. As a pwms having had 4 full doses of Ocrelizumab over 2 years, would it be worth trying to swap to a different DMT given that COVID isn’t going anywhere any time soon? Is this a conversation we, as patients on anti CD20 DMTs should be having with our neurologists or after 2 years of treatment should we instead try to mitigate our risk now through things we can control such as exercise and healthy eating?

    • We need to see vaccinated data, quoting MD antibodies aren’t that important ;). You have a better trained T-cell army because of Ocrelizumab.

  • on Ocrevus, MS nurse says I should be out and about meeting friends, family and that I am at no more risk of catching/being ill with, than everybody else. Said I shouldn’t postpone next infusion cos they have no idea when boosters are coming out ( I believe the Gov has already said it starts next month and immunosupressed are in the first of the two groups). I know T-cells might kind of protect me, but I am sitting here with my mouth agape after talking to her.

    Do these people never read any of the studies/papers that are coming out?

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