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Anti-CD20 Therapy for MS and NMOSD Linked to Lower COVID-19 Antibody Response

Disease Spotlight | <b>Disease Spotlight: NMOSD</b>

Among independent variables including DMT group, time from COVID-19 infection, total IgG level, age, sex, obesity, and COVID-19 severity, only the anti-CD20 group was associated with decreased odds of positive serology.

Despite observing a high SARS-CoV-2 seroconversion rate among patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD), those treated with an anti-CD20 therapy had a seroconversion rate 2 times as low as untreated patients or patients receiving a non-anti-CD20 disease modifying therapy (DMT). According to the study authors, these findings, while heterogenous in nature, warrant monitoring the long-term risk of reinfection and specific vaccination strategies for patients within these populations.1

Senior author Valerie Pourcher, MD, PhD, associate professor, Hôpital de la Pitié Salpêtrière, and colleagues collected blood samples of 119 patients (115 MS, 4 NMOSD; mean age, 43 years) diagnosed with COVID-19 between February 19, 2020, and February 26, 2021. Index of anti-S lgA, anti-N lgG; titer of anti-S IgG; and levels of IgG, IgA, and IgM were compared between groups of patients with several DMTs using 1-way analysis of variance (ANOVA) and subsequent t-test for 1-by-1 group comparisons if needed.

Overall, seroconversion rate was 80.6% (n = 96) within 5 months (standard deviation [SD], 3.4) after infection. Specific subanalysis showed that those on anti-CD20 therapies had lower anti-S IgG positivity (P <.001), lower anti-S IgG titer (P <.001), lower anti-S IgA positivity (P = .05), and a lower anti-N IgG positivity (P <.001) in comparison to other DMT groups. Notably, there were no observed differences on such outcomes between the other DMT subgroups.

"Postvaccination serological follow-up studies will be necessary to investigate the potential effect of anti-CD20 and other DMTs on humoral response to SARS-CoV-2 vaccine and eventually to adapt the vaccine strategy,” Pourcher et al wrote. "Importantly, the association between the time from last anti-CD20 infusion and the seroconversion may lead to recommend anti-COVID-19 vaccination timing as far as possible from anti-CD20 infusion, for example, starting from 4 months after infusion.”

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Among the 3 levels of DMTs (anti-CD20, n = 21; other DMTs, n = 77; no DMT, n = 21), only 47.6% (n = 10) of those on anti-CD20 had at least 1 SARS-CoV-2 Ig positivity, in comparison to 85.7% (n = 66) for patients on other DMTs and 95.2% (n = 20) for patients not on DMTs (P <.001).

After finding no correlation between time from COVID-19 and anti-S IgG titer (P = .82), investigators performed linear regressions to test whether this finding holds at the level of each DMT group. Not only did patients on anti-CD20 show a higher rate of anti-S IgG decrease over time, but a trend was found for an interaction between time and DMT group (P = .06) for these patients compared with the 2 other groups after adding the variable “time by DMT group.”

Among independent variables including DMT group, time from COVID-19, total IgG level, age, sex, obesity, and COVID-19 severity, only those on anti-CD20 therapies were associated with a decreased odd of positive serology (odds ratio, 0.07 [95% CI, 0.01-0.69]; P = .02).

Using the same variables, found that being on an anti-CD20 was associated with a decreased anti-S IgG titer (estimate, –1.06 [95% CI, –1.79 to –0.34]; P = .004), while hospitalization for COVID-19 was also associated with a decreased anti-S IgG titer (estimate, –0.97 [95% CI, –1.86 to –0.08]; P = .03). Additionally, total IgG level was also positively associated with anti-S IgG titer (estimate, 0.16 [95% CI, 0-0.32]; P = .05). Although not significant, investigators did observe a positive association between obesity and anti-S IgG titer (estimate, 0.89 [95% CI, –0.09 to 1.81]; P = .08).

There has been previous research published regarding anti-CD20 use among patients with MS throughout the COVID-19 pandemic. A study from Sormani et al showed that anti-CD20 agents such as ocrelizumab (Ocrevus; Genentech) or rituximab (Rituxan; Genentech/Biogen) may lead to an increased risk of severe COVID-19. Methylprednisolone treatment within the last month was also associated with a worse outcome.2Humoral response of patients with MS who have received mRNA-COVID-19 vaccines while being treated with DMTs were also identified by another group of researchers earlier this year. They found that only cladribine (Mavenclad; EMD Serono) was the only DMT to not impair humoral response.3

REFERENCES
1. Louapre C, Ibrahim M, Maillart E, et al. Anti-CD20 therapies decrease humoral immune response to SARS-CoV-2 in patients with multiple sclerosis or neuromyelitis optica spectrum disorders. J Neurol Neurosurg Psychiatry. Published online August 2, 2021. doi: 10.1136/jnnp-2021-326904
2. Sormani MP, Rossi ND, Schiavetti I, et al. Disease‐modifying therapies and coronavirus disease 2019 severity in multiple sclerosis. Ann Neurol. 2021; 89(4). doi: 10.1002/ana.26028
3. Achiron A, Mandel M, Dreyer-Alster S, et al. Humoral immune response to COVID-19 mRNA vaccine in patients with multiple sclerosis treated with high-efficacy disease-modifying therapies. Ther Adv Neurol Disord. Published online April 22, 2021. doi: 10.1177/17562864211012835