Publications by authors named "Zoe van Kempen"

Importance: Increasing numbers of people with multiple sclerosis (MS) use disease-modifying therapy (DMT). Long-term stable disease while taking such medications provides a rationale for considering DMT discontinuation given patient burden, costs, and potential adverse effects of immunomodulating therapy.

Objective: To investigate whether first-line DMT can be safely discontinued in patients with long-term stable MS.

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Background: Biomarkers of neuronal and axonal damage (serum neurofilament light (sNfL) and serum glial fibrillary acidic protein (sGFAP)) may provide insight into the aetiology of natalizumab wearing-off symptoms (WoSs).

Objectives: We investigated the longitudinal association between and predictive value of sNfL and sGFAP and the occurrence of WoS in MS patients treated with natalizumab.

Methods: We performed longitudinal measurements of sNfL and sGFAP in NEXT-MS trial participants who completed a questionnaire about WoS.

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Article Synopsis
  • Serum neurofilament light (sNfL) serves as a biomarker for neuro-axonal damage in multiple sclerosis (MS) but its clinical usage is still limited; this study assessed how its implementation affects clinical decisions at the MS Center Amsterdam.
  • Over the study period (August 2021-December 2022), sNfL was evaluated in various contexts, with a notable change in clinical decisions in 19.3% of cases, especially when assessing new symptoms or when higher sNfL levels were present.
  • The findings suggest that integrating sNfL into clinical practice improved decision-making certainty and potentially adjusted expectations regarding MRI activity, indicating its potential value in patient care while calling for further research
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Background: Higher age is associated with less inflammatory disease activity in relapsing-remitting multiple sclerosis (RRMS). It is unknown whether age itself or disease duration underlies this association.

Objectives: This study investigated the effects of age, disease duration, and inflammatory disease activity in people with RRMS.

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Article Synopsis
  • * Ongoing randomized controlled trials are exploring different approaches to dosing ocrelizumab, including higher doses, personalized B-cell dosing, and potential treatment discontinuation.
  • * The proposed roadmap aims to use trial outcomes to improve understanding and effectiveness of anti-CD20 therapies, addressing existing knowledge gaps in MS treatment.
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Background: Several studies reported lower drug concentrations with subcutaneous natalizumab compared to intravenous natalizumab. With the emergence of extended interval dosing, gaining more insight into lower concentrations after subcutaneous administration is essential.

Methods: We compared serum trough concentrations between subcutaneous and intravenous administration within a matched cohort (n = 50).

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Background: Despite impaired humoral response in patients treated with immunosuppressants (ISPs), recent studies found similar severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection compared to controls. One potential explanation is the rapid generation of humoral response on infection, but evidence is lacking.

Objectives: We investigated the longitudinal dynamics of the SARS-CoV-2 antibody repertoire after SARS-CoV-2 delta and omicron breakthrough infection in patients with immune-mediated inflammatory diseases (IMIDs) receiving ISP therapy and controls.

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Article Synopsis
  • mRNA vaccines effectively protect against SARS-CoV-2 in healthy individuals, but their effectiveness in multiple sclerosis (MS) patients treated with ocrelizumab (OCR) is unclear.
  • A study found that 63% of OCR-treated MS patients did not produce detectable antibodies after vaccination, and they showed lower antibody responses compared to healthy subjects.
  • The research suggests that scheduling vaccinations carefully for OCR-treated patients can improve their immune responses, highlighting potential markers (CD38 and HLA-DR) for assessing vaccine efficacy in these patients.
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Background: The noninflammatory immunoglobulin G4 (IgG4) is linked to tolerance and is unique to humans. Although poorly understood, prolonged antigenic stimulation and IL-4-signaling along the T helper 2-axis may be instrumental in IgG4 class switching. Recently, repeated SARS-CoV-2 mRNA vaccination has been linked to IgG4 skewing.

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Background: Extended interval dosing (EID) of natalizumab treatment is increasingly used in multiple sclerosis. Besides the clear anti-inflammatory effect, natalizumab is considered to have neuroprotective properties as well.

Objectives: This study aimed to study the longitudinal effects of EID compared to standard interval dosing (SID) and natalizumab drug concentrations on brain atrophy.

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One reason for a lack of response to rituximab as well as infusion-related anaphylactic adverse events is the development of antidrug Abs to rituximab. Besides rituximab, a number of other therapeutic Abs targeting CD20 are nowadays available as alternatives. In this study, we investigated the potential cross-reactivity of (human) anti-rituximab Abs to three other anti-CD20 mAbs: ofatumumab, obinutuzumab, and ocrelizumab.

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Hirayama disease is a self-limiting cervical motor neuron disease, usually affecting the spinal cord at level C7-T1. We share an unusual case of Hirayama disease in a young man affecting roots C4-C6. He presented in coma due to diaphragm weakness and hypercapnic respiratory failure.

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Background: Extended interval dosing (EID) of natalizumab is a promising strategy to optimise treatment in multiple sclerosis (MS). Personalised EID by therapeutic drug monitoring can enable further extension of treatment intervals.

Methods: The NEXT-MS trial is an investigator-initiated prospective phase IV non-randomised study.

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Background: Humoral responses after SARS-CoV-2 vaccination are greatly impaired in multiple sclerosis (MS) patients on fingolimod. Effects of repeated vaccination and infections on long-term responses are unclear.

Methods: Prospective study in 60 MS patients on fingolimod measuring humoral responses after up to four vaccinations and 8 months after fourth vaccination.

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Background: Recent studies suggest that extended interval dosing of ocrelizumab, an anti-B cell therapy, does not affect its clinical effectiveness in most patients with multiple sclerosis (MS). However, it remains to be established whether certain B cell subsets are differentially repopulated after different dosing intervals and whether these subsets relate to clinical efficacy.

Methods: We performed high-dimensional single-cell characterization of the peripheral immune landscape of patients with MS after standard (SID; n = 43) or extended interval dosing (EID; n = 37) of ocrelizumab and in non-ocrelizumab-treated (control group, CG; n = 28) patients with MS, using mass cytometry by time of flight (CyTOF).

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Background: There is a need in Relapsing-Remitting Multiple Sclerosis (RRMS) treatment for biomarkers that monitor neuroinflammation, neurodegeneration, treatment response, and disease progression despite treatment.

Objective: To assess the value of serum glial fibrillary acidic protein (sGFAP) as a biomarker for clinical disease progression and brain volume measurements in natalizumab-treated RRMS patients.

Methods: sGFAP and neurofilament light (sNfL) were measured in an observational cohort of natalizumab-treated RRMS patients at baseline, +3, +12, and +24 months and at the last sample follow-up (median 5.

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Background: Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressants (ISPs) may have impaired long-term humoral immune responses and increased disease activity after SARS-CoV-2 infection. We aimed to investigate long-term humoral immune responses against SARS-CoV-2 and increased disease activity after a primary SARS-CoV-2 infection in unvaccinated IMID patients on ISPs.

Methods: IMID patients on active treatment with ISPs and controls (i.

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Background: Focal inflammatory disease activity in relapsing-remitting multiple sclerosis (RRMS) diminishes with increasing age. Here we use patient-level data from randomised controlled trials (RCTs) of natalizumab treatment in RRMS to investigate the association of age and inflammatory disease activity.

Methods: We used patient-level data from the AFFIRM (natalizumab vs placebo in relapsing-remitting MS, NCT00027300) and SENTINEL (natalizumab plus interferon beta vs interferon beta in relapsing remitting MS, NCT00030966) RCTs.

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Background And Purpose: Inflammatory disease activity in multiple sclerosis (MS) decreases with advancing age. Previous work found a decrease in contrast-enhancing lesions (CELs) with age. Here, we describe the relation of age and magnetic resonance imaging (MRI) measures of inflammatory disease activity during long-term follow-up in a large real-world cohort of people with relapse onset MS.

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Background: The majority of patients with multiple sclerosis on ocrelizumab have B-cell depletion after standard interval dosing of 26 weeks. With B-cell-guided dosing patients receive their next dose when B-cell repopulation occurs. Prediction of B-cell repopulation using ocrelizumab concentrations could aid in personalising treatment regimes.

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Background: Natalizumab is effective in the treatment of multiple sclerosis (MS). In 2021, the European Medicines Agency approved the subcutaneous (SC) variant of natalizumab which can be used instead of intravenous administration. However, the course of drug levels varies between administration routes, and the Food and Drug Administration rejected the request for approval of natalizumab SC for reasons that were not disclosed.

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For patients with immune-mediated inflammatory diseases (IMIDs), concerns exist about increased disease activity after vaccination. We aimed to assess changes in disease activity after SARS-CoV-2 vaccination in patients with IMIDs, and determine risk factors for increased disease activity. In this substudy of a prospective observational cohort study (Target-to-B!), we included patients with IMIDs who received a SARS-CoV-2 vaccine.

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Background: It is unclear which patients with multiple sclerosis (MS) are most susceptible for omicron breakthrough infections.

Methods: We assessed omicron breakthrough infections in vaccinated patients with MS with and without disease-modifying therapies enrolled in an ongoing large prospective study. We longitudinally studied humoral responses after primary and booster vaccinations and breakthrough infections.

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