- |||||||||| Mavenclad (cladribine) / EMD Serono, Lemtrada (alemtuzumab) / Sanofi
[VIRTUAL] DiseaseModifying Therapies for the Treatment of RelapsingRemitting Multiple Sclerosis: A Comparison of Their Efficacy for Reducing Relapse Rate () - Mar 6, 2021 - Abstract #ACTRIMSForum2021ACTRIMS_Forum_225;
Although treatment responses varied, as well as comparators, the evaluated injectable, infused, and oral DMTs all provided a significant clinical benefit for relapse rate reduction. Innovations in the targeting/sequential monotherapy/escalation therapy/combination therapies towards the personalization of RRMS treatment will likely improve further the outcomes of patients with RRMS; future research in this regard is warranted in clinical trial and real-world settings.
- |||||||||| Lemtrada (alemtuzumab) / Sanofi
Journal: PTPN22 Acts in a Cell Intrinsic Manner to Restrict the Proliferation and Differentiation of T Cells Following Antibody Lymphodepletion. (Pubmed Central) - Mar 4, 2021
Similarly, in man lymphopenia induced by mAb therapy, for instance Alemtuzumab as treatment for Multiple Sclerosis, can precipitate development of secondary autoimmune disease in up to 30 % of patients...Using bone marrow chimeric mice, we showed that PTPN22 influenced development of both regulatory and effector T cell functions in a cell-intrinsic manner. Overall the expansion of Tregs is likely to keep the expanded T effector populations in check and sparing Treg during therapeutic mAb depletion may be a useful strategy to prevent occurrence of secondary autoimmunity.
- |||||||||| Lemtrada (alemtuzumab) / Sanofi
Journal: Acquired haemophilia A after alemtuzumab treatment of multiple sclerosis. (Pubmed Central) - Mar 3, 2021
Overall the expansion of Tregs is likely to keep the expanded T effector populations in check and sparing Treg during therapeutic mAb depletion may be a useful strategy to prevent occurrence of secondary autoimmunity. No abstract available
- |||||||||| Lemtrada (alemtuzumab) / Sanofi
Clinical, Review, Journal: Differential Effects of MS Therapeutics on B Cells-Implications for Their Use and Failure in AQP4-Positive NMOSD Patients. (Pubmed Central) - Feb 23, 2021
While lately approved disease-modifying drugs like ocrelizumab deplete B cells directly, most MS medications were not primarily designed to target B cells...In contrast, drugs such as natalizumab and interferon-β, which lead to activation and accumulation of B cells in the peripheral blood, lack efficacy or even induce catastrophic disease activity in NMOSD. Hence, we conclude that the differential effect of MS drugs on B cells is one potential parameter determining the therapeutic efficacy or failure in antibody-dependent diseases like seropositive NMOSD.
- |||||||||| Lemtrada (alemtuzumab) / Sanofi
FDA event, Review, Journal: Molecular Effects of FDA-Approved Multiple Sclerosis Drugs on Glial Cells and Neurons of the Central Nervous System. (Pubmed Central) - Feb 20, 2021
Furthermore, we point to a possible common molecular effect of these drugs, namely a key role for NFκB signaling, causing a switch from pro-inflammatory microglia and astrocytes to anti-inflammatory phenotypes of these CNS cell types that recently emerged as central players in MS pathogenesis. This notion argues for the need to further explore the molecular mechanisms underlying MS drug action.
- |||||||||| Campath (alemtuzumab) / Sanofi, Lemtrada (alemtuzumab) / Sanofi
Clinical, PK/PD data, Journal: Lymphocyte pharmacodynamics are not associated with autoimmunity or efficacy after alemtuzumab. (Pubmed Central) - Feb 16, 2021
P3
Repopulation kinetics of the evaluated peripheral lymphocyte subsets did not predict autoimmune AE occurrence or disease activity, including return of disease activity after 2 alemtuzumab courses. Further study is needed to investigate potential antigen-level markers of treatment response.
- |||||||||| Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi, Lemtrada (alemtuzumab) / Sanofi, autologous hematopoietic stem cell therapy / Northwestern University
[VIRTUAL] OUTCOME OF NON-MYELOABLATIVE AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR MULTIPLE SCLEROSIS: A SINGLE CENTER SUMMARY OF 511 PATIENTS (On-Demand Library) - Feb 4, 2021 - Abstract #EBMT2021EBMT_2152;
The low incidence of bacteremia may be related to the use of non-myeloablative regimens that do not cause mucositis, i.e. gut endothelium bacterial barrier remains closed, placement and removal of the large bore apheresis catheter on the same day and subsequent insertion of a PICC line in the upper inner arm on day of admission resulting in less risk of cutaneous barrier breaches, a HEPA-filtered floor, and to the use of pre-emptive antibiotics when neutropenic. On the other hand, one patient developed legionella pneumonia that was subsequently cultured from the showerhead.
- |||||||||| Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi, Lemtrada (alemtuzumab) / Sanofi, autologous hematopoietic stem cell therapy / Northwestern University
[VIRTUAL] OUTCOME OF NON-MYELOABLATIVE AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR MULTIPLE SCLEROSIS: A SINGLE CENTER SUMMARY OF 511 PATIENTS (On-Demand Library) - Feb 4, 2021 - Abstract #EBMT2021EBMT_2151;
The low incidence of bacteremia may be related to the use of non-myeloablative regimens that do not cause mucositis, i.e. gut endothelium bacterial barrier remains closed, placement and removal of the large bore apheresis catheter on the same day and subsequent insertion of a PICC line in the upper inner arm on day of admission resulting in less risk of cutaneous barrier breaches, a HEPA-filtered floor, and to the use of pre-emptive antibiotics when neutropenic. On the other hand, one patient developed legionella pneumonia that was subsequently cultured from the showerhead.
- |||||||||| Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi, Lemtrada (alemtuzumab) / Sanofi, autologous hematopoietic stem cell therapy / Northwestern University
[VIRTUAL] OUTCOME OF NON-MYELOABLATIVE AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR MULTIPLE SCLEROSIS: A SINGLE CENTER SUMMARY OF 511 PATIENTS (On-Demand Library) - Feb 4, 2021 - Abstract #EBMT2021EBMT_2150;
The low incidence of bacteremia may be related to the use of non-myeloablative regimens that do not cause mucositis, i.e. gut endothelium bacterial barrier remains closed, placement and removal of the large bore apheresis catheter on the same day and subsequent insertion of a PICC line in the upper inner arm on day of admission resulting in less risk of cutaneous barrier breaches, a HEPA-filtered floor, and to the use of pre-emptive antibiotics when neutropenic. On the other hand, one patient developed legionella pneumonia that was subsequently cultured from the showerhead.
- |||||||||| Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi, Lemtrada (alemtuzumab) / Sanofi, autologous hematopoietic stem cell therapy / Northwestern University
[VIRTUAL] OUTCOME OF NON-MYELOABLATIVE AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR MULTIPLE SCLEROSIS: A SINGLE CENTER SUMMARY OF 511 PATIENTS (On-Demand Library) - Feb 4, 2021 - Abstract #EBMT2021EBMT_2149;
The low incidence of bacteremia may be related to the use of non-myeloablative regimens that do not cause mucositis, i.e. gut endothelium bacterial barrier remains closed, placement and removal of the large bore apheresis catheter on the same day and subsequent insertion of a PICC line in the upper inner arm on day of admission resulting in less risk of cutaneous barrier breaches, a HEPA-filtered floor, and to the use of pre-emptive antibiotics when neutropenic. On the other hand, one patient developed legionella pneumonia that was subsequently cultured from the showerhead.
- |||||||||| Mavenclad (cladribine) / EMD Serono, Lemtrada (alemtuzumab) / Sanofi
Review, Journal: Multiple Sclerosis and SARS-CoV-2 Vaccination: Considerations for Immune-Depleting Therapies. (Pubmed Central) - Feb 3, 2021
In this review, we summarize the immunological effects of immune-depleting therapy and underlying considerations for the hitherto existing recommendations that suggest a restricted use of immune-deleting therapies during the pandemic. Moreover, we critically discuss open questions regarding vaccination in general and against SARS-CoV-2 in pwMS.
- |||||||||| Campath (alemtuzumab) / Sanofi, Lemtrada (alemtuzumab) / Sanofi
[VIRTUAL] An Unusual Etiology of Graves’ Disease: Alemtuzumab (On-Demand) - Feb 2, 2021 - Abstract #ENDO2021ENDO_2021;
For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO 2021.
- |||||||||| Campath (alemtuzumab) / Sanofi, Lemtrada (alemtuzumab) / Sanofi
[VIRTUAL] Alemtuzumab-Induced Hypothyroidism Presenting in Pregnancy - the First 2 Reported Cases (On-Demand) - Feb 2, 2021 - Abstract #ENDO2021ENDO_1922;
Conclusion To optimise pregnancy outcomes, we recommend that women previously treated with alemtuzumab should be screened monthly for thyroid dysfunction during a subsequent pregnancy. The neonatal team should be alert to transient neonatal thyroid dysfunction, which, like spontaneous alloimmune neonatal thyroid disease, appears to settle spontaneously.
- |||||||||| Tysabri (natalizumab) / Biogen, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Clinical, Journal: Effect of switching from natalizumab to moderate- vs high-efficacy DMT in clinical practice. (Pubmed Central) - Jan 30, 2021
Of the patients included in the study, 48.6% switched to Mod DMT (dimethyl fumarate, n = 130; fingolimod, n = 140) vs 23.4% who switched to HET (ocrelizumab, n = 106; rituximab, n = 17; alemtuzumab, n = 7)...By 24 months post-NTZ, there was no difference in the annualized relapse rate (OR = 1.44, 95% CI [0.69-1.59], p = 0.334) or time to first clinical relapse (HR = 2.12, 95% CI [0.87-5.17], p = 0.090), although switchers to Mod DMT had higher gadolinium-enhancing (GdE) lesions (OR = 3.62, 95% CI [1.56-5.21], p = 0.005), earlier time to first GdE lesion (HR = 6.67, 95% CI [2.06-9.16], p = 0.002), lower proportion with the absence of disease activity (OR = 0.41, 95% CI [0.21-0.71], p = 0.004), and higher risk of disability progression on T25FW (OR = 1.83, 95% CI [1.06-3.02], p = 0.043) and 9-HPT (OR = 1.81, 95% CI [1.05-3.56], p = 0.044). Patients switching from NTZ to Mod DMT vs HET were at relatively increased risk of disease activity within the first 6 months of NTZ withdrawal that was sustained at 24 months, yielding greater disability progression.
- |||||||||| Tysabri (natalizumab) / Biogen, Lemtrada (alemtuzumab) / Sanofi
Clinical, Journal, Adverse events: Comparison of Pharmaceutical Effect of Alemtuzumab and Natalizumab and Their Side Effects in Treatment of Various Stages of Multiple Sclerosis Patients. (Pubmed Central) - Jan 30, 2021
According to the results, the efficacy of Natalizumab in treating RRMS patients was better than Alemtuzumab, while there were no significant differences between other stages of MS patients. Also, the autologous hematopoietic stem cell transplantation method is more effective than Alemtuzumab and Natalizumab to use as the best treatment for patients with MS can give a theoretical and clinical guide for various stages of MS treatment and provide them to specialists.
- |||||||||| Lemtrada (alemtuzumab) / Sanofi
[VIRTUAL] Vaccination Responses in Setting of Different Types of MS DMTs (Scientific Program Auditorium) - Jan 27, 2021 - Abstract #ACTRIMSForum2021ACTRIMS_Forum_47;
Cell-depleting therapies, including those that deplete B-cells (egaCD20, cladribine, alemtuzumab) are likely not to impact pre-existing humoralimmunity, but expected to attenuate vaccine induced antibody responses. We will review the variousconsiderations which, while awaiting more definitive data, may provide somehelpful guidance in striving to provide people living with MS with protectionfrom COVID-19 while maintaining control of their MS disease activity.
- |||||||||| Lemtrada (alemtuzumab) / Sanofi
Trial completion date, Trial primary completion date: LEMTRADA Pregnancy Registry in Multiple Sclerosis (clinicaltrials.gov) - Jan 27, 2021
P=N/A, N=204, Recruiting,
We will review the variousconsiderations which, while awaiting more definitive data, may provide somehelpful guidance in striving to provide people living with MS with protectionfrom COVID-19 while maintaining control of their MS disease activity. Trial completion date: Nov 2022 --> Nov 2026 | Trial primary completion date: Nov 2022 --> Nov 2026
- |||||||||| Lemtrada (alemtuzumab) / Sanofi
Journal: Stem cell transplantation and alemtuzumab - options for "early reprogramming" in multiple sclerosis? (Pubmed Central) - Jan 26, 2021
Trial completion date: Nov 2022 --> Nov 2026 | Trial primary completion date: Nov 2022 --> Nov 2026 Autologous hematopoietic stem cell transplantation (aHSCT) has been repeatedly studied for treating multiple sclerosis (MS), yet evidence remains complicated as treatment was often administered to heterogenic patient collectives and in later stages of MS.
- |||||||||| Lemtrada (alemtuzumab) / Sanofi
Journal, IO biomarker: Age-Related Lymphocyte Output During Disease-Modifying Therapies for Multiple Sclerosis. (Pubmed Central) - Jan 23, 2021
Autologous hematopoietic stem cell transplantation (aHSCT) has been repeatedly studied for treating multiple sclerosis (MS), yet evidence remains complicated as treatment was often administered to heterogenic patient collectives and in later stages of MS. This observational study indicated that different age-related changes of the new T and B lymphocyte production could be one of the reasons for the emergence, in the real-world setting, of adverse events not otherwise observed in clinical trials; thus, caution is advised when choosing disease-modifying therapies for multiple sclerosis patients.
- |||||||||| Lemtrada (alemtuzumab) / Sanofi
Clinical, Journal: Pneumocystis pneumonia in a patient treated with alemtuzumab for relapsing multiple sclerosis. (Pubmed Central) - Jan 21, 2021
We report a patient who developed PJP two months after receiving the first course of Lemtrada, and fully recovered after receiving cotrimoxazole treatment. We should remain vigilant of opportunistic infections in patients who develop pneumonitis and evaluate the need for PJP prophylaxis during Lemtrada treatment.
- |||||||||| Lemtrada (alemtuzumab) / Sanofi
Clinical, Journal: Switching from fingolimod to alemtuzumab in patients with highly active relapsing-remitting multiple sclerosis: Α case series. (Pubmed Central) - Jan 21, 2021
We should remain vigilant of opportunistic infections in patients who develop pneumonitis and evaluate the need for PJP prophylaxis during Lemtrada treatment. Alemtuzumab appears to be an effective and safe short-term therapeutic option both as a rescue therapy for the disease flare-up associated with fingolimod withdrawal, as well as for the reversal of the deteriorating course observed in patients who fail treatment with fingolimod.
- |||||||||| Lemtrada (alemtuzumab) / Sanofi
Journal: The impact of diagnostic criteria and treatments on the 20-year costs for treating relapsing-remitting multiple sclerosis. (Pubmed Central) - Jan 21, 2021
Alemtuzumab appears to be an effective and safe short-term therapeutic option both as a rescue therapy for the disease flare-up associated with fingolimod withdrawal, as well as for the reversal of the deteriorating course observed in patients who fail treatment with fingolimod. DMTs remain the main responsible for increased medical direct costs in MS, whilst improved diagnostic skills and subsequent patient profiling can at least in part mitigate costs for MS treatment and management.
- |||||||||| Lemtrada (alemtuzumab) / Sanofi
Journal: Alemtuzumab significantly improves posterior fossa syndrome presented as a relapse of multiple sclerosis. (Pubmed Central) - Jan 21, 2021
DMTs remain the main responsible for increased medical direct costs in MS, whilst improved diagnostic skills and subsequent patient profiling can at least in part mitigate costs for MS treatment and management. Our case highlights the significant and rapid effect of Alemtuzumab therapy on both cognitive and motor symptoms occurring during a MS relapse with atypical neuroradiological localization.
- |||||||||| Lemtrada (alemtuzumab) / Sanofi
[VIRTUAL] The use of Autologous Haematopoietic Stem Cell Transplants in patients with Relapsing Remitting Multiple Sclerosis (RRMS): A Meta‐Analysis () - Jan 5, 2021 - Abstract #BSHI2020BSH-I_270;
Objective To investigate the safety and efficacy of administering autologous haematopoietic stem cell transplants (AHSCT) in patients who have been diagnosed with relapsing remitting multiple sclerosis (RRMS) as an alternative to current disease modifying therapies (DMTs) such as Alemtuzumab and Interferons...The benefits are seen particularly in younger patients, particularly those with a lower EDSS, a shorter disease duration and patients who have not yet progressed to secondary progressive MS. With this study along with additional trials, particularly with adverse effects and long‐term outcomes beyond 5 years as primary outcomes, it is hoped that AHSCT with become a mainstream treatment for patients with early‐stage RRMS.
- |||||||||| Mavenclad (cladribine) / EMD Serono, Lemtrada (alemtuzumab) / Sanofi
Clinical, Review, Journal: Safety of Newer Disease Modifying Therapies in Multiple Sclerosis. (Pubmed Central) - Jan 2, 2021
However, they are associated with safety concerns and subsequent monitoring requirements. Adverse events are initially observed in phase 2 and 3 clinical trials, and further long-term data are collected in phase 3 extension studies, case series, and post-marketing reports, which highlight the need to periodically re-evaluate and adjust monitoring strategies to optimize treatment safety in an individualized approach.
- |||||||||| Lemtrada (alemtuzumab) / Sanofi
Clinical, Journal: COVID-19 in a multiple sclerosis (MS) patient treated with alemtuzumab: Insight to the immune response after COVID. (Pubmed Central) - Dec 31, 2020
Adverse events are initially observed in phase 2 and 3 clinical trials, and further long-term data are collected in phase 3 extension studies, case series, and post-marketing reports, which highlight the need to periodically re-evaluate and adjust monitoring strategies to optimize treatment safety in an individualized approach. This report shows that MS patients with mild depletion of B and T cells can mount an antiviral response against COVID-19 and produce IgG.
- |||||||||| Kesimpta (ofatumumab subcutaneous) / Novartis, Genmab, Zeposia (ozanimod) / BMS, Lemtrada (alemtuzumab) / Sanofi
Journal: Ozanimod (Zeposia) for multiple sclerosis. (Pubmed Central) - Dec 30, 2020
This report shows that MS patients with mild depletion of B and T cells can mount an antiviral response against COVID-19 and produce IgG. No abstract available
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Review, Journal: A new era for monoclonal antibodies with applications in neurology (Review). (Pubmed Central) - Dec 29, 2020
These innovative therapies are more effective and can treat previously untreatable diseases. As better understanding of the pathogenic mechanisms of neurological diseases is gained, additional mAbs are expected to be developed at a lower cost and with better safety profile compared with current treatment options.
- |||||||||| Lemtrada (alemtuzumab) / Sanofi
Trial completion: TOPAZ: Phase IIIB-IV Long-Term Follow-up Study for Patients Who Participated in CAMMS03409 (clinicaltrials.gov) - Dec 28, 2020
P4, N=812, Completed,
As better understanding of the pathogenic mechanisms of neurological diseases is gained, additional mAbs are expected to be developed at a lower cost and with better safety profile compared with current treatment options. Active, not recruiting --> Completed
- |||||||||| Lemtrada (alemtuzumab) / Sanofi
Trial completion date, Trial termination, Trial primary completion date: Assessing the Induction of Long-term Immune Regulation Following Treatment With Lemtrada (clinicaltrials.gov) - Dec 17, 2020
P=N/A, N=97, Terminated,
Thereby, the understanding of the mechanisms of action of alemtuzumab will improve its efficacy and safety for present and future patients. Trial completion date: Sep 2023 --> Nov 2020 | Recruiting --> Terminated | Trial primary completion date: Sep 2022 --> Nov 2020; Study funding was terminated.
- |||||||||| Lemtrada (alemtuzumab) / Sanofi
Review, Journal: The Role of TH17 Cells in Multiple Sclerosis: Therapeutic Implications. (Pubmed Central) - Dec 16, 2020
Fingolimod and alemtuzumab induce a paramount decrease in central memory T cells, which harbour the majority of peripheral TH17 cells, while the efficacy of natalizumab, dimethyl fumarate and importantly hematopoietic stem cell therapy correlates with TH17.1 cell inhibition...Moreover, recovery rates of TH cells best correlate with long-term efficacy after therapeutical immunodepletion. We conclude that central memory TH17.1 cells play a pivotal role in MS pathogenesis and they represent a major target of MS therapeutics.
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