Longitudinal humoral response in MS patients treated with cladribine tablets after receiving the second and third doses of SARS-CoV-2 mRNA vaccine

Brill, Livnat; Rechtman, Ariel; Shifrin, Alla; Rozenberg, Ayal; Афанасьєв, С. М.; Zveik, Omri; Haham, Nitzan; Levin, Neta; Vaknin‐Dembinsky, Adi

doi:10.1016/j.msard.2022.103863

Cited by 7 publications

(7 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with other studies involving different pwMS ( 8 , 32 – 34 ), the first main result of our study was that pwMS treated with DMTs develop a positive humoral immune response to the mRNA vaccine, which does not differ significantly from that observed in HD. Moreover, an increase in humoral response in pwMS following the third dose of BNT162b2 mRNA vaccine was seen.…”

Section: Discussionsupporting

confidence: 91%

Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine

et al. 2022

View full text Add to dashboard Cite

BackgroundThe mRNA vaccines help protect from COVID-19 severity, however multiple sclerosis (MS) disease modifying therapies (DMTs) might affect the development of humoral and T-cell specific response to vaccination.MethodsThe aim of the study was to evaluate humoral and specific T-cell response, as well as B-cell activation and survival factors, in people with MS (pwMS) under DMTs before (T0) and after two months (T1) from the third dose of vaccine, comparing the obtained findings to healthy donors (HD). All possible combinations of intracellular IFNγ, IL2 and TNFα T-cell production were evaluated, and T-cells were labelled “responding T-cells”, those cells that produced at least one of the three cytokines of interest, and “triple positive T-cells”, those cells that produced simultaneously all the three cytokines.ResultsThe cross-sectional evaluation showed no significant differences in anti-S antibody titers between pwMS and HD at both time-points. In pwMS, lower percentages of responding T-cells at T0 (CD4: p=0.0165; CD8: p=0.0022) and triple positive T-cells at both time-points compared to HD were observed (at T0, CD4: p=0.0007 and CD8: p=0.0703; at T1, CD4: p=0.0422 and CD8: p=0.0535). At T0, pwMS showed higher plasma levels of APRIL, BAFF and CD40L compared to HD (p<0.0001, p<0.0001 and p<0.0001, respectively) and at T1, plasma levels of BAFF were still higher in pwMS compared to HD (p=0.0022).According to DMTs, at both T0 and T1, lower anti-S antibody titers in the depleting/sequestering-out compared to the enriching-in pwMS subgroup were found (p=0.0410 and p=0.0047, respectively) as well as lower percentages of responding CD4+ T-cells (CD4: p=0.0394 and p=0.0004, respectively). Moreover, the depleting/sequestering-out subgroup showed higher percentages of IFNγ-IL2-TNFα+ T-cells at both time-points, compared to the enriching-in subgroup in which a more heterogeneous cytokine profile was observed (at T0 CD4: p=0.0187; at T0 and T1 CD8: p =0.0007 and p =0.0077, respectively).ConclusionIn pwMS, humoral and T-cell response to vaccination seems to be influenced by the different DMTs. pwMS under depleting/sequestering-out treatment can mount cellular responses even in the presence of a low positive humoral response, although the cellular response seems qualitatively inferior compared to HD. An understanding of T-cell quality dynamic is needed to determine the best vaccination strategy and in general the capability of immune response in pwMS under different DMT.

show abstract

Section: Discussionsupporting

confidence: 91%

Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine

et al. 2022

View full text Add to dashboard Cite

show abstract

“…In one study, IgG levels were significantly lower 1 month after the vaccine dose compared with healthy controls, 29 whereas in a different study, IgG levels were comparable between patients treated with cladribine and untreated patients. 28 In addition, among a small subset of patients treated with cladribine tablets during phase IV of the MAGNIFY-MS (Evaluation of the onset of action in highly active MS; ClinicalTrials.gov identifier: NCT03364036) and CLOCK-MS (Cladribine tablets: Collaborative study to evaluate impact on central nervous system biomarkers in multiple sclerosis; ClinicalTrials.gov Identifier: NCT03963375) studies who received vaccination for seasonal influenza and varicella zoster virus as standard care, seroprotective antibody titres were either maintained or increased following vaccination.…”

Section: Safety Of Cladribine Tablets In Multiple Sclerosismentioning

confidence: 82%

“…7 Most patients are expected to recover to either normal lymphocyte counts or grade 1 lymphopenia within 9 months. 7 Published pharmacovigilance data to date do not indicate a more serious disease course or more severe outcomes for patients treated with cladribine tablets who acquire COVID-19 compared with the general population or other patients with MS. 24 Evidence indicates that patients receiving cladribine tablets can produce antibodies in response to COVID-19 vaccination; [25][26][27][28][29] data from a meta-analysis of observational studies indicated that 97.2% of patients receiving cladribine had positive COVID-19 antibody results. 28 Furthermore, following the second and third vaccination with a COVID-19 mRNA vaccine, a sustained positive humoral response has been observed in patients with MS receiving cladribine tablets.…”

Section: Safety Of Cladribine Tablets In Multiple Sclerosismentioning

confidence: 99%

“…28 Furthermore, following the second and third vaccination with a COVID-19 mRNA vaccine, a sustained positive humoral response has been observed in patients with MS receiving cladribine tablets. 29 It is still unclear whether patients with MS receiving cladribine tablets have immunoglobulin (Ig) G levels comparable to healthy patients. All comparisons versus placebo.…”

Section: Safety Of Cladribine Tablets In Multiple Sclerosismentioning

confidence: 99%

See 1 more Smart Citation

Cladribine Tablets: A Review of the Practical Considerations in Multiple Sclerosis Nursing Practice

Thomas¹,

Barker²,

Brownlee³

et al. 2022

US Neurology

View full text Add to dashboard Cite

Nurses specializing in the care of patients with multiple sclerosis (MS) are uniquely positioned to provide personalized care. Patients prescribed cladribine tablets (taken for ≤10 days per year for 2 years), indicated for adults with highly active relapsing MS in the EU and Australia, can benefit from an active partnership with their healthcare professionals, including MS nurses, who can promote an understanding of and the adherence to treatment. In clinical studies, patients treated with cladribine tablets had lower annual relapse rates, greater odds of being relapse free, a longer time to sustained progression of disability and a significant reduction in radiological disease activity compared with patients receiving placebo. Patients should be advised that, although everyone will have a different experience, the safety of cladribine tablets is supported by 16 years of clinical trial and post-approval data. Furthermore, there is no indication of a more serious disease course or more severe outcomes for patients with MS treated with cladribine tablets who acquire coronavirus disease 2019 compared with the general population or other patients with MS. This article presents practical considerations that may help achieve a greater understanding of the potential benefits and drawbacks of MS treatment, build the patient–nurse relationship, encourage shared decision-making and ultimately may improve care.

show abstract

“…While pregnancy must be ruled out during the treatment periods, women with optimized disease control can conceive 6 months after the last dose [30]. The treatment-free period also offers a window for vaccinations, albeit first real-world data suggest a vaccination response following cladribine treatment regardless of the time of application and the lymphocyte count [31,32]. The concept of pulsed selective immune reconstitution therapy has a lower treatment burden, less cumulative risk, a favorable risk-benefit ratio, and attested high treatment convenience due to short courses of oral application.…”

Section: Evidence Review Of Long-term Efficacy and Benefits Of Pulsed...mentioning

confidence: 99%

Long-term management of multiple sclerosis patients treated with cladribine tablets beyond year 4

Meuth

Bayas

Kallmann³

et al. 2022

Expert Opinion on Pharmacotherapy

View full text Add to dashboard Cite

Introduction:Oral cladribine is a highly effective pulsed selective immune reconstitution therapy licensed for relapsing multiple sclerosis (RMS) since 2017. A full treatment course comprises two treatment cycles given 1 year apart, followed by two treatment-free years. The management of cladribine-treated patients beyond year 4 needs to be addressed as patients have now passed the initial 4 years since European Medical Agency approval. Areas covered: A panel of neurologists and a neuroradiologist experienced in MS treatment/monitoring evaluated clinical trial data and real-world evidence and proposed recommendations for the management of cladribine-treated patients beyond year 4. Expert opinion: Continuous monitoring of disease activity during the treatment-free period is important. Subsequent management depends on the presence or absence of inflammatory disease activity, determined in the absence of consistent guidelines via practice-driven neurological decision criteria. Persisting or newly occurring inflammatory disease activity is an indication for further treatment, i.e. either re-initiation of cladribine or switching to another highly effective disease-modifying therapy. The decision to retreat or switch should be based on clinical and radiological evaluation considering disease course, treatment history, and safety aspects. In the absence of disease activity, either retreatment can be offered, or the treatment-free period can be extended under structured monitoring.

show abstract

Longitudinal humoral response in MS patients treated with cladribine tablets after receiving the second and third doses of SARS-CoV-2 mRNA vaccine

Cited by 7 publications

References 27 publications

Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine

Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine

Cladribine Tablets: A Review of the Practical Considerations in Multiple Sclerosis Nursing Practice

Long-term management of multiple sclerosis patients treated with cladribine tablets beyond year 4

Contact Info

Product

Resources

About