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The International Journal of... Mar 2019Sporadic inclusion body myositis is the most common inflammatory myopathy over the age of 50. The aetiopathogenesis of the disease remains unclear and to the day there... (Review)
Review
BACKGROUND
Sporadic inclusion body myositis is the most common inflammatory myopathy over the age of 50. The aetiopathogenesis of the disease remains unclear and to the day there is no effective treatment.
OBJECTIVES
The aim of the present review is to present the latest data on the new insights and developments in the treatment of sporadic inclusion body myositis, focusing on Bimagrumab and Alemtuzumab.
METHODS
For the purpose of the review we searched multiple internet databases in order to find the most recent studies and clinical trials on the safety, tolerability and efficacy of Bimagrumab and Alemtuzumab in sporadic inclusion body myositis.
RESULTS
We found four trials on Bimagrumab, with one of them being an extension phase III study, and one small series trial on Alemtuzumab. The first clincopathological trial on Bimagrumab showed promising evidence, which were partially confirmed by the double-blinded controlled multicentre trial, however the primary endpoint of improving 6-m walking distance or improving the muscle strength has not been reached. The evidence from the Alemtuzumab trial was also promising, but the risk of bias of the study was relatively high, because it was open labelled, the number of patient was low and the yearly disease progression was much higher than in other recent studies.
CONCLUSIONS
Although both Bimagrumab and Alemtuzumab were well tolerated and showed promising results, the Bimagrumab trial did not reach the primary endpoint, and the Alemtuzumab trial has a relatively high risk of bias and the results need to be interpreted with caution.
Topics: Alemtuzumab; Antibodies, Blocking; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Humans; Immunologic Factors; Myositis, Inclusion Body
PubMed: 30238817
DOI: 10.1080/00207454.2018.1527329 -
Multiple Sclerosis and Related Disorders Jan 2020
Topics: Adult; Alemtuzumab; Cerebrovascular Disorders; Cohort Studies; Cytokine Release Syndrome; Female; Humans; Immunologic Factors; Male; Multiple Sclerosis, Relapsing-Remitting
PubMed: 32172992
DOI: 10.1016/j.msard.2019.101412 -
JAMA Neurology Jun 2016
Topics: Alemtuzumab; Humans; Interferon-beta; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting
PubMed: 27042804
DOI: 10.1001/jamaneurol.2016.0259 -
BMC Neurology Sep 2020Identifying causes of alemtuzumab induced respiratory symptoms in Multiple Sclerosis (MS) patients is crucial.
BACKGROUND
Identifying causes of alemtuzumab induced respiratory symptoms in Multiple Sclerosis (MS) patients is crucial.
CASE PRESENTATION
We report a case of diffuse alveolar damage (DAD) in a patient with MS after the first course of alemtuzumab treatment. A 42-year-old female developed progressive non-productive cough and exertional dyspnea 2 months after alemtuzumab treatment. DAD was diagnosed histopathologically by lung biopsy. The patient recovered completely, alemtuzumab was not continued.
CONCLUSIONS
Our case highlights another pathomechanism for non-infective lung-disorders in alemtuzumab treated MS patients. DAD is a potential, albeit rare side effect of alemtuzumab, broadening the spectrum of non-infective lung disorders that should be considered in the diagnostic work-up.
Topics: Adult; Alemtuzumab; Antineoplastic Agents, Immunological; Female; Humans; Lung Diseases, Interstitial; Multiple Sclerosis, Relapsing-Remitting; Pulmonary Alveoli
PubMed: 32967641
DOI: 10.1186/s12883-020-01934-7 -
Journal of Neurology Nov 2018Alemtuzumab is a humanized anti-CD52 monoclonal antibody approved in more than 65 countries for the treatment of relapsing-remitting multiple sclerosis (RRMS). Compared... (Review)
Review
Alemtuzumab is a humanized anti-CD52 monoclonal antibody approved in more than 65 countries for the treatment of relapsing-remitting multiple sclerosis (RRMS). Compared with subcutaneous interferon-beta-1a, alemtuzumab significantly reduced clinical disease activity and the rate of brain volume loss, and improved disability outcomes in patients with active RRMS who were either treatment naive (CARE-MS I study) or who had an inadequate response (≥ 1 relapse after ≥ 6 months of treatment) to prior therapy (CARE-MS II study). Adverse events (AEs) associated with alemtuzumab include infusion-associated reactions, infections, and autoimmunity. The most commonly reported autoimmune AEs observed with alemtuzumab involve the thyroid gland, followed by immune thrombocytopenia and nephropathies. A monitoring program was designed and implemented to facilitate the early detection of autoimmune events to ensure timely and adequate management. The aim of this article is to provide physicians (including neurologists, general practitioners, endocrinologists, hematologists, and nephrologists who may be less familiar with the symptoms and treatment of autoimmune events), with practical real-world recommendations for the monitoring and management of autoimmunity associated with alemtuzumab treatment.
Topics: Alemtuzumab; Autoimmunity; Disease Management; Humans; Immunologic Factors; Monitoring, Immunologic; Multiple Sclerosis, Relapsing-Remitting; Practice Guidelines as Topic
PubMed: 29525836
DOI: 10.1007/s00415-018-8822-y -
Journal of Cardiovascular Pharmacology... Sep 2019The use of alemtuzumab for induction therapy in orthotopic heart transplantation remains controversial, despite its observed benefits in other transplant populations.... (Comparative Study)
Comparative Study
The use of alemtuzumab for induction therapy in orthotopic heart transplantation remains controversial, despite its observed benefits in other transplant populations. This study aimed to evaluate whether alemtuzumab conferred a lower risk of rejection while reducing toxicities commonly attributed to standard immunosuppression in orthotopic heart transplantation. We included adult patients who underwent orthotopic heart transplantation and received induction therapy with alemtuzumab (n = 26) or standard immunosuppression (n = 26). The primary end point was freedom from grade ≥2 rejection at 12 months. Baseline characteristics were similar between the groups with the exception of poorer renal function in the alemtuzumab group ( < .05). The primary end point of freedom from grade ≥2 rejection at 12 months was not different between alemtuzumab and standard therapy (76.9% vs 96.2%, = .077), likely due to similarities in the rates of antibody-mediated rejection in the 2 groups. However, grade ≥2 acute cellular rejection was considerably lower with alemtuzumab (0% vs 19.2%, = .02), as was acute cellular rejection of any severity (50% vs 7.7%, = .004). Deterioration in renal function was significantly greater among patients receiving standard therapy as evidenced by decreases in glomerular filtration rate (-25.6 vs -9.2 mL/min, = .032). No differences in hematologic or infectious complications were observed. In conclusion, alemtuzumab reduced several important rejection-related outcomes while ameliorating the toxicities associated with standard immunosuppression therapy, making it a promising agent for induction in orthotopic heart transplantation.
Topics: Adult; Aged; Alemtuzumab; Drug Therapy, Combination; Female; Graft Rejection; Graft Survival; Heart Transplantation; Humans; Immunosuppressive Agents; Kidney; Kidney Diseases; Male; Middle Aged; Progression-Free Survival; Retrospective Studies; Risk Factors; Time Factors
PubMed: 31035777
DOI: 10.1177/1074248419841635 -
International Journal of Environmental... Jul 2021Alopecia Universalis (AU) is the most severe form of Alopecia Areata and is caused by cytotoxic T-cells reacting with follicular autoantigens, producing complete loss of... (Review)
Review
Alopecia Universalis (AU) is the most severe form of Alopecia Areata and is caused by cytotoxic T-cells reacting with follicular autoantigens, producing complete loss of scalp and body hair. Alemtuzumab is a highly efficacious monoclonal antibody used in the treatment of Multiple Sclerosis (MS), but it causes secondary autoimmunity in up to 40% of patients. Many factors are believed to contribute to this process, but pathogenic mechanisms are not well clear. To date, three cases of AU after treatment with Alemtuzumab have been reported. In this paper we report the cases of two patients who developed AU 12 months after the second cycle of Alemtuzumab, with a review of the literature. One year after the end of the second cycle, two female patients in their thirties experienced complete hair loss. The first case was temporally associated with a significant drop in vitamin D (VD) levels. The second case was accompanied by joint swelling. Both patients had thyroid alterations and showed no hair regrowth after a 2-year follow-up. AU must be considered among the secondary autoimmune manifestations of Alemtuzumab treatment. We emphasize the need for appropriate patient screening and thorough clinical surveillance for factors predisposing patients to secondary autoimmunity.
Topics: Alemtuzumab; Alopecia; Alopecia Areata; Female; Follow-Up Studies; Humans; Multiple Sclerosis
PubMed: 34299789
DOI: 10.3390/ijerph18147338 -
Journal of Neuroimmunology May 2023Immune responses in the central nervous system (CNS) are highly compartmentalized and cerebrospinal fluid (CSF) in particular often reflects CNS pathology better than...
BACKGROUND AND OBJECTIVES
Immune responses in the central nervous system (CNS) are highly compartmentalized and cerebrospinal fluid (CSF) in particular often reflects CNS pathology better than peripheral blood. While CSF leukocytes are known to be distinct from blood, the immediate effects of peripheral leukocyte depletion on CSF leukocytes have not been studied in humans.
METHODS
We here analyzed CSF and blood from two relapsing-remitting multiple sclerosis (RRMS) patients early after peripheral leukocyte depletion with the anti-CD52 antibody alemtuzumab compared to untreated RRMS and control patients using single cell RNA-sequencing.
RESULTS
As expected for alemtuzumab, most leukocyte lineages including T cells were synchronously depleted from CSF and blood, while - surprisingly - pDCs were maintained in CSF but depleted from blood by alemtuzumab. Transcriptionally, genes associated with migration were elevated only in the CSF after alemtuzumab. Predicted cellular interactions indicated a central role of pDCs and enhanced migration signaling in the CSF after alemtuzumab.
DISCUSSION
The CSF and blood compartments are thus partially uncoupled, emphasizing that the CNS is only partially accessible even for treatments profoundly affecting the blood.
Topics: Humans; Alemtuzumab; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Central Nervous System
PubMed: 37062182
DOI: 10.1016/j.jneuroim.2023.578088 -
Immunotherapy Feb 2022We report on the presentation and outcome of a 28-year-old female who developed red cell aplasia following alemtuzumab therapy for relapsing remitting multiple...
We report on the presentation and outcome of a 28-year-old female who developed red cell aplasia following alemtuzumab therapy for relapsing remitting multiple sclerosis. The patient also developed synchronous immune thrombocytopenia and immune neutropenia, but not aplastic anemia. This patient received high dose steroids, intravenous immunoglobulin (iv.Ig), rituximab, red cell transfusions, vincristine, G-CSF, cyclosporin and mycophenolate to treat the combination of cytopenias over a period of 6 months with subsequent improvement in bone marrow function. While alemtuzumab has several recognized autoimmune complications, little is known about the potential hematological side effects. The combination of red cell aplasia, immune thrombocytic purpura and autoimmune neutropenia has not previously been described in the literature following alemtuzumab immunotherapy and highlights the importance of monthly blood monitoring post alemtuzumab administration.
Topics: Adrenal Cortex Hormones; Adult; Alemtuzumab; Antineoplastic Agents, Immunological; Cyclosporine; Female; Granulocyte Colony-Stimulating Factor; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Multiple Sclerosis, Relapsing-Remitting; Mycophenolic Acid; Neutropenia; Purpura, Thrombocytopenic, Idiopathic; Red-Cell Aplasia, Pure; Rituximab; Treatment Outcome; Vincristine
PubMed: 34743591
DOI: 10.2217/imt-2021-0163 -
Neurology(R) Neuroimmunology &... Nov 2020To determine whether the punctuated administration of low-dose rituximab, temporally linked to B-cell hyperrepopulation (defined when the return of CD19 B cells...
OBJECTIVE
To determine whether the punctuated administration of low-dose rituximab, temporally linked to B-cell hyperrepopulation (defined when the return of CD19 B cells approximates 40%-50% of baseline levels as measured before alemtuzumab treatment inception), can mitigate alemtuzumab-associated secondary autoimmunity.
METHODS
In this hypothesis-driven pilot study, 10 patients received low-dose rituximab (50-150 mg/m), a chimeric anti-CD20 monoclonal antibody, after either their first or second cycles of alemtuzumab. These patients were then routinely assessed for the development of autoimmune disorders and safety signals related to the use of dual monoclonal antibody therapy.
RESULTS
Five patients received at least 1 IV infusion of low-dose rituximab, following alemtuzumab therapy, with a mean follow-up of 41 months. None of the 5 patients developed secondary autoimmune disorders. An additional 5 patients with follow-up over less than 24 months received at least 1 infusion of low-dose rituximab treatment following alemtuzumab treatment. No secondary autoimmune diseases were observed.
CONCLUSIONS
An anti-CD20 "whack-a-mole" B-cell depletion strategy may serve to mitigate alemtuzumab-associated secondary autoimmunity in MS by reducing the imbalance in B- and T-cell regulatory networks during immune reconstitution. We believe that these observations warrant further investigation.
CLASSIFICATION OF EVIDENCE
This study provides Class IV evidence that for people with MS, low-dose rituximab following alemtuzumab treatment decreases the risk of alemtuzumab-associated secondary autoimmune diseases.
Topics: Adult; Alemtuzumab; Autoimmune Diseases; B-Lymphocytes; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Immunologic Factors; Male; Middle Aged; Multiple Sclerosis; Outcome Assessment, Health Care; Pilot Projects; Rituximab
PubMed: 32769201
DOI: 10.1212/NXI.0000000000000868