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

Author(s):

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.

Valerie Pourcher, MD, PhD

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.”

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