Personalized B-cell tailored dosing of ocrelizumab in patients with multiple sclerosis during the COVID-19 pandemic

Lierop, Zoë Y. G. J. van; Toorop, Alyssa A; Ballegoij, Wouter J. C. van; Dubbelink, Tom B. G. Olde; Strijbis, Eva; Jong, Brigit A. de; Oosten, B.W. van; Moraal, Bastiaan; Teunissen, Charlotte E.; Uitdehaag, Bernard M. J.; Killestein, Joep; Kempen, Zoé L E van

doi:10.1177/13524585211028833

Cited by 39 publications

(27 citation statements)

References 9 publications

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“…Anti‐CD20 monoclonal antibodies were the DMTs most strongly associated with lack of seroconversion following the COVID‐19 vaccination. Their high efficacy and relatively favorable safety profile has offered a welcome addition to the MS DMT landscape; however, once ocrelizumab is commenced, rapid and profound B‐cell depletion occurs, with few people repopulating B‐cells prior to their 6 months interval infusion 11,12 . These drugs have previously been shown to be associated with attenuated humoral response to recall and novel vaccinations 2 .…”

Section: Discussionmentioning

confidence: 99%

COVID‐19 Vaccine Response in People with Multiple Sclerosis

Tallantyre

Vickaryous

Anderson

et al. 2021

Annals of Neurology

127

115

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Objective The purpose of this study was to investigate the effect of disease modifying therapies on immune response to severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) vaccines in people with multiple sclerosis (MS). Methods Four hundred seventy‐three people with MS provided one or more dried blood spot samples. Information about coronavirus disease 2019 (COVID‐19) and vaccine history, medical, and drug history were extracted from questionnaires and medical records. Dried blood spots were eluted and tested for antibodies to SARS‐CoV‐2. Antibody titers were partitioned into tertiles with people on no disease modifying therapy as a reference. We calculated the odds ratio of seroconversion (univariate logistic regression) and compared quantitative vaccine response (Kruskal Wallis) following the SARS‐CoV‐2 vaccine according to disease modifying therapy. We used regression modeling to explore the effect of vaccine timing, treatment duration, age, vaccine type, and lymphocyte count on vaccine response. Results Compared to no disease modifying therapy, the use of anti‐CD20 monoclonal antibodies (odds ratio = 0.03, 95% confidence interval [CI] = 0.01–0.06, p < 0.001) and fingolimod (odds ratio = 0.04; 95% CI = 0.01–0.12) were associated with lower seroconversion following the SARS‐CoV‐2 vaccine. All other drugs did not differ significantly from the untreated cohort. Both time since last anti‐CD20 treatment and total time on treatment were significantly associated with the response to the vaccination. The vaccine type significantly predicted seroconversion, but not in those on anti‐CD20 medications. Preliminary data on cellular T‐cell immunity showed 40% of seronegative subjects had measurable anti‐SARS‐CoV‐2 T cell responses. Interpretation Some disease modifying therapies convey risk of attenuated serological response to SARS‐CoV‐2 vaccination in people with MS. We provide recommendations for the practical management of this patient group. ANN NEUROL 2021

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Section: Discussionmentioning

confidence: 99%

COVID‐19 Vaccine Response in People with Multiple Sclerosis

Tallantyre

Vickaryous

Anderson

et al. 2021

Annals of Neurology

127

115

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“…Generally, based on previous reports, CD20 depleting agents have been delayed by 1-3 months during the COVID-19 pandemic, and no major rebound in disease activity has been reported [10,[22][23][24]. Specifically, a recent German report evaluated the clinical consequences of EID in RRMS patients treated with OCR during the COVID-19 pandemic, comparing patients on EID (defined as ≥ 4-week delay of dose interval) with a control group on SID during the same period (January to December 2020) [10].…”

Section: Discussionmentioning

confidence: 99%

Is It Time for Ocrelizumab Extended Interval Dosing in Relapsing Remitting MS? Evidence from An Italian Multicenter Experience During the COVID-19 Pandemic

Zanghì¹,

Avolio

Signoriello

et al. 2022

Neurotherapeutics

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In the COVID-19 pandemic era, safety concerns have been raised regarding the risk of severe infection following administration of ocrelizumab (OCR), a B-cell-depleting therapy. We enrolled all relapsing remitting multiple sclerosis (RRMS) patients who received maintenance doses of OCR from January 2020 to June 2021. Data were extracted in December 2021. Standard interval dosing (SID) was defined as a regular maintenance interval of OCR infusion every 6 months, whereas extended interval dosing (EID) was defined as an OCR infusion delay of at least 4 weeks. Three infusions were considered in defining SID vs. EID (infusions A, B, and C). Infusion A was the last infusion before January 2020. The primary study outcome was a comparison of disease activity during the A-C interval, which was defined as either clinical (new relapses) or radiological (new lesions on T1-gadolinium or T2-weighted magnetic resonance imaging (MRI) sequences). Second, we aimed to assess confirmed disability progression (CDP). A total cohort of 278 patients (174 on SID and 104 on EID) was enrolled. Patients who received OCR on EID had a longer disease duration and a higher rate of vaccination against severe acute respiratory syndrome-coronavirus 2 (p < 0.05). EID was associated with an increased risk of MRI activity during the A-C interval (OR 5.373, 95% CI 1.203–24.001, p = 0.028). Being on SID or EID did not influence CDP (V-Cramer 0.47, p = 0.342). EID seemed to be associated with a higher risk of MRI activity in our cohort. EID needs to be carefully considered for OCR-treated patients.

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“…4 Some favoured other high-efficacy treatments such as natalizumab instead of anti-CD20 therapies 5 while others successfully implemented extended-interval dosing of anti-CD20 therapies. 6,7 Van Lierop ZYGJ et al personalized ocrelizumab treatment in 159 patients by re-dosing when CD19 B-cell count was over 10 cells/μL. No patients developed relapses and only two (1.9%) had magnetic resonance imaging (MRI) activity.…”

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confidence: 99%

“…No patients developed relapses and only two (1.9%) had magnetic resonance imaging (MRI) activity. 7 PwMS and especially those receiving immunosuppressive treatments have been considered a vulnerable group since the beginning of the pandemic. How pwMS have adapted to the changes and restrictions of the pandemic has also been addressed by researchers.…”

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confidence: 99%