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Multiple Sclerosis and Related Disorders Jul 2020Medications are indicated to minimize adverse reactions with alemtuzumab treatment for multiple sclerosis, but polypharmacy can be problematic. We characterized...
Medications are indicated to minimize adverse reactions with alemtuzumab treatment for multiple sclerosis, but polypharmacy can be problematic. We characterized prescriptions filled by 160 individuals before, during and after first infusion of alemtuzumab (Dec/2013-Jun/2017). Ninety-five percent of individuals filled ≥1 prescription(s) before alemtuzumab across 87 unique drug classes, averaging 5.3 prescriptions/person over 47 weeks. During the infusion period, 90% filled ≥1 prescription(s) for 40 new drug classes, averaging 2.2 prescriptions/person over 5 weeks. Twenty-four percent refilled ≥1 of these prescription(s) after alemtuzumab across 17 drug classes, averaging 0.3 refills/person over 24 weeks. There was substantial medication burden throughout the study.
Topics: Adult; Alemtuzumab; British Columbia; Drug Prescriptions; Female; Humans; Immunologic Factors; Male; Middle Aged; Multiple Sclerosis; Polypharmacy; Prospective Studies
PubMed: 32403069
DOI: 10.1016/j.msard.2020.102086 -
The New England Journal of Medicine Jun 2019
Topics: Aged; Alemtuzumab; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Arrhythmias, Cardiac; Female; Humans; Melanoma; Myocarditis; Programmed Cell Death 1 Receptor
PubMed: 31189042
DOI: 10.1056/NEJMc1903064 -
Annals of Hematology Nov 2023
Topics: Humans; Multiple Sclerosis; Alemtuzumab; Hemophilia A; Antineoplastic Agents, Immunological
PubMed: 37481472
DOI: 10.1007/s00277-023-05370-8 -
Frontiers in Immunology 2019Treatment with alemtuzumab is followed by an early increase in Treg frequencies. Whether naïve and memory subsets are differentially affected and how depletion...
Treatment with alemtuzumab is followed by an early increase in Treg frequencies. Whether naïve and memory subsets are differentially affected and how depletion influences dysfunctional MS-Treg is unclear. In this study, we analyzed the effect of alemtuzumab on regulatory T-cells (Treg) in patients with multiple sclerosis (MS). For this purpose 182 blood samples from 25 MS patients were taken shortly before treatment and serially for up to 24 months after two alemtuzumab cycles. We studied Treg by flow cytometry (quantitation, phenotypical characterization), real-time polymerase chain reaction (T-cell receptor (TCR) excision circles [TREC] content), CDR3-spectratyping (clonal distribution), and proliferation assays (suppressive function). CD52-mediated cytolysis of Treg and conventional T-cells was determined by a complement-dependent cytolysis assay. Our studies revealed that 1 week post-alemtuzumab, Treg were depicted at constant frequencies among CD4 T-cells. In contrast, Treg frequencies were massively increased at month 1. Post-depletional Treg exhibited a CD45RO memory phenotype, a skewed TCR repertoire, and contained minimum TREC numbers. Naïve Treg, thymic markers, and TCR-variability commenced to rise after 6 months but did not attain baseline levels. , Treg exhibited higher susceptibility to lysis than Tcon. Treg suppressive function constantly increased within 1 year when co-cultured with syngeneic T-cells, but remained stable against allogeneic T-cells from normal donors. Our findings suggest that (1) Treg are not spared from alemtuzumab-mediated depletion and thymopoiesis does not considerably contribute to long-term recovery, (2) either homeostatic proliferation and/or conversion from residual Tcon contributes to Treg expansion during the early post-treatment phase (3) the enhanced inhibitory effect of Treg following alemtuzumab is due to altered composition and reactivity of post-depletional Tcon.
Topics: Adolescent; Adult; Alemtuzumab; Antineoplastic Agents, Immunological; Biomarkers; CD4 Lymphocyte Count; Cytotoxicity, Immunologic; Female; Humans; Immunologic Memory; Immunomodulation; Immunophenotyping; Lymphocyte Depletion; Male; Middle Aged; Multiple Sclerosis; Receptors, Antigen, T-Cell; T-Lymphocytes, Regulatory; Treatment Outcome; Young Adult
PubMed: 31214176
DOI: 10.3389/fimmu.2019.01204 -
Clinical Endocrinology Sep 2022Alemtuzumab-induced autoimmune thyroid events (AIATEs) are the most common adverse effects observed in relapsing-remitting multiple sclerosis (RRMS) patients. This study...
OBJECTIVE
Alemtuzumab-induced autoimmune thyroid events (AIATEs) are the most common adverse effects observed in relapsing-remitting multiple sclerosis (RRMS) patients. This study aims to explore the clinical and biochemical characteristics of such AIATEs, and to examine the risk factors for their occurrence, particularly for the worst clinical phenotype of fluctuating Graves' disease (GD).
DESIGN, PATIENTS, MEASUREMENTS
We retrospectively analysed a real-life single-centre consecutive series of 57 RRMS patients treated with alemtuzumab whose clinical and biochemical parameters were collected before starting the treatment and then monthly during their follow-up.
RESULTS
AIATEs developed in 39% of patients a mean 17 months ± 11 after the first cycle of alemtuzumab. The most common AIATEs were GD (64%), followed by Hashimoto's thyroiditis with hypothyroidism (23%), TSH-receptor-antibody (TRAb)-positive hypothyroidism (9%), and silent thyroiditis (4%). GD showed a fluctuating course in 57% of cases. Baseline positivity for anti-thyroperoxidase antibodies, and higher absolute titers of anti-thyroglobulin and anti-thyroperoxidase antibodies correlated significantly with the risk of developing AIATEs, but TRAb positivity did not. Higher TRAb titers at the time of GD being diagnosed correlated strongly with a greater risk of the fluctuating GD phenotype. On ROC curve analysis, we found that a cut-off of 7.3 IU/L could be used to predict the risk of developing a fluctuating GD, with a positive predictive value of 100%.
CONCLUSIONS
TRAb levels measured with commercial automatic methods at the time of a patient being diagnosed with alemtuzumab-induced GD emerged as a novel biomarker for predicting a fluctuating disease phenotype, with an influence on subsequent therapeutic decisions and patients' follow-up.
Topics: Alemtuzumab; Graves Disease; Humans; Hypothyroidism; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Retrospective Studies; Thyroiditis
PubMed: 34724236
DOI: 10.1111/cen.14616 -
European Thyroid Journal Apr 2024Secondary thyroid autoimmunity, especially Graves' disease (GD), frequently develops in patients with multiple sclerosis (MS) following alemtuzumab treatment (ALTZ;...
INTRODUCTION
Secondary thyroid autoimmunity, especially Graves' disease (GD), frequently develops in patients with multiple sclerosis (MS) following alemtuzumab treatment (ALTZ; anti-CD52). Thyroid eye disease (TED) can also develop, and rituximab (RTX; anti-CD20) is a suitable treatment.
CASE PRESENTATION
A 37-year-old woman with MS developed steroid-resistant active moderate-to-severe TED 3 years after ALTZ, that successfully responded to a single 500 mg dose of i.v. RTX. Before RTX peripheral B-cells were low, and were totally depleted immediately after therapy. Follow-up analysis 4 years post ALTZ and 1 year post RTX showed persistent depletion of B cells, and reduction of T regulatory cells in both peripheral blood and thyroid tissue obtained at thyroidectomy.
CONCLUSION
RTX therapy successfully inactivated TED in a patient with low B-cell count derived from previous ALTZ treatment. B-cell depletion in both thyroid and peripheral blood was still present 1 year after RTX, indicating a likely cumulative effect of both treatments.
Topics: Female; Humans; Adult; Rituximab; Graves Ophthalmopathy; Alemtuzumab; Antibodies, Monoclonal, Murine-Derived; Graves Disease; Multiple Sclerosis
PubMed: 38471303
DOI: 10.1530/ETJ-23-0236 -
Experimental and Clinical... Oct 2023Alemtuzumab is a monoclonal antibody against CD52 that is being increasingly used in renal transplantation as a lymphocyte-depleting agent. Data on alemtuzumab use in...
Alemtuzumab is a monoclonal antibody against CD52 that is being increasingly used in renal transplantation as a lymphocyte-depleting agent. Data on alemtuzumab use in resistant rejection episodes are scarce, especially in children. Here, we present a 14-year-old renal transplant patient with acute cellular and humoral rejection who was treated with pulse steroids, plasmapheresis, and intravenous immunoglobulin with no success. He had 2 previous rejection episodes that were treated with antithymocyte globulin. In the third episode, alemtuzumab was given as a rescue therapy, and the patient benefited from the treatment. No complications were observed. Alemtuzumab can be a treatment option in pediatric patients with refractory rejection episodes.
Topics: Male; Humans; Child; Adolescent; Alemtuzumab; Kidney Transplantation; Immunosuppressive Agents; Antibodies, Monoclonal, Humanized; Immunosuppression Therapy; Graft Rejection
PubMed: 30806200
DOI: 10.6002/ect.2018.0203 -
Neurology Feb 2018
Topics: Alemtuzumab; Antibodies, Monoclonal; Disease Progression; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Multiple Sclerosis
PubMed: 29352097
DOI: 10.1212/WNL.0000000000004969 -
Frontiers in Immunology 2020Rabbit anti-thymocyte globulin (rATG) is currently the treatment of choice for glucocorticoid-resistant, recurrent, or severe acute allograft rejection (AR). However,... (Comparative Study)
Comparative Study
Rabbit anti-thymocyte globulin (rATG) is currently the treatment of choice for glucocorticoid-resistant, recurrent, or severe acute allograft rejection (AR). However, rATG is associated with severe infusion-related side effects. Alemtuzumab is incidentally given to kidney transplant recipients as treatment for AR. In the current study, the outcomes of patients treated with alemtuzumab for AR were compared with that of patients treated with rATG for AR. The patient-, allograft-, and infection-free survival and adverse events of 116 alemtuzumab-treated patients were compared with those of 108 patients treated with rATG for AR. Propensity scores were used to control for differences between the two groups. Patient- and allograft survival of patients treated with either alemtuzumab or rATG were not different [hazard ratio (HR) 1.14, 95%-confidence interval (CI) 0.48-2.69, = 0.77, and HR 0.82, 95%-CI 0.45-1.5, = 0.52, respectively). Infection-free survival after alemtuzumab treatment was superior compared with that of rATG-treated patients (HR 0.41, 95%-CI 0.25-0.68, < 0.002). Infusion-related adverse events occurred less frequently after alemtuzumab treatment. Alemtuzumab therapy may therefore be an alternative therapy for glucocorticoid-resistant, recurrent, or severe acute kidney transplant rejection.
Topics: Adult; Alemtuzumab; Allografts; Antilymphocyte Serum; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Retrospective Studies
PubMed: 32719676
DOI: 10.3389/fimmu.2020.01332 -
Neurology(R) Neuroimmunology &... Jul 2020To test the hypothesis that antidrug antibodies (ADAs) against alemtuzumab could become relevant after repeated treatments for some individuals, possibly explaining...
OBJECTIVE
To test the hypothesis that antidrug antibodies (ADAs) against alemtuzumab could become relevant after repeated treatments for some individuals, possibly explaining occasional treatment resistance.
METHODS
Recombinant alemtuzumab single-chain variable fragment antibody with a dual tandem nanoluciferase reporter linker was made and used to detect binding ADAs. Alemtuzumab immunoglobulin G Alexa Fluor 488 conjugate was used in a competitive binding cell-based assay to detect neutralizing ADAs. The assays were used to retrospectively screen, blinded, banked serum samples from people with MS (n = 32) who had received 3 or more cycles of alemtuzumab. Lymphocyte depletion was measured between baseline and about 1 month postinfusion.
RESULTS
The number of individuals showing limited depletion of lymphocytes increased with the number of treatment cycles. Lack of depletion was also a poor prognostic feature for future disease activity. ADA responses were detected in 29/32 (90.6%) individuals. Neutralizing antibodies occurred before the development of limited depletion in 6/7 individuals (18.8% of the whole sample). Preinfusion, ADA levels predicted limited, postinfusion lymphocyte depletion.
CONCLUSIONS
Although ADAs to alemtuzumab have been portrayed as being of no clinical significance, alemtuzumab-specific antibodies appear to be clinically relevant for some individuals, although causation remains to be established. Monitoring of lymphocyte depletion and the antidrug response may be of practical value in patients requiring additional cycles of alemtuzumab. ADA detection may help to inform on retreatment or switching to another treatment.
Topics: Adult; Alemtuzumab; Antibodies; Female; Humans; Immunologic Factors; Male; Middle Aged; Multiple Sclerosis; Outcome Assessment, Health Care; Retrospective Studies
PubMed: 32499328
DOI: 10.1212/NXI.0000000000000767