Adverse events with fatal outcome associated with alemtuzumab treatment in multiple sclerosis

Holmøy, Trygve; Fevang, Børre; Olsen, David B.; Spigset, Olav; Liu, Bo

doi:10.1186/s13104-019-4507-6

Cited by 37 publications

(21 citation statements)

References 17 publications

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“…Late adverse events of ALZ and AHSCT have been described after treatment of MS, including both infectious and autoimmune complications as well as treatment-related mortality. [26][27][28][29][30][31] Late adverse events of grade 3 or higher were uncommon in both cohorts. Nearly half of the patients treated with ALZ had an autoimmune adverse event, compared with 20% in the AHSCT group; this constitutes the major difference in the late adverse events between the groups.…”

Section: Discussionmentioning

confidence: 89%

Autologous haematopoietic stem cell transplantation compared with alemtuzumab for relapsing–remitting multiple sclerosis: an observational study

Zhukovsky

Sandgren

Silfverberg

et al. 2020

J Neurol Neurosurg Psychiatry

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ObjectiveTo compare outcomes after treatment with autologous haematopoietic stem cell transplantation (AHSCT) and alemtuzumab (ALZ) in patients with relapsing–remitting multiple sclerosis.MethodsPatients treated with AHSCT (n=69) received a conditioning regimen of cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulinerG (6.0 mg/kg). Patients treated with ALZ (n=75) received a dose of 60 mg over 5 days, a repeated dose of 36 mg over 3 days after 1 year and then as needed. Follow-up visits with assessment of the expanded disability status scale score, adverse events and MR investigations were made at least yearly.ResultsThe Kaplan-Meier estimates of the primary outcome measure ‘no evidence of disease activity’ was 88% for AHSCT and 37% for ALZ at 3 years, p<0.0001. The secondary endpoint of annualised relapse rate was 0.04 for AHSCT and 0.1 for ALZ, p=0.03. At last follow-up, the proportions of patients who improved, were stable or worsened were 57%/41%/1% (AHSCT) and 45%/43%/12% (ALZ), p=0.06 Adverse events grade three or higher were present in 48/69 patients treated with AHSCT and 0/75 treated with ALZ in the first 100 days after treatment initiation. The most common long-term adverse event was thyroid disease with Kaplan-Meier estimates at 3 years of 21% for AHSCT and 46% for ALZ, p=0.005.ConclusionsIn this observational cohort study, treatment with AHSCT was associated with a higher likelihood of maintaining ‘no evidence of disease activity’. Adverse events were more frequent with AHSCT in the first 100 days, but thereafter more common in patients treated with ALZ.

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Section: Discussionmentioning

confidence: 89%

Autologous haematopoietic stem cell transplantation compared with alemtuzumab for relapsing–remitting multiple sclerosis: an observational study

Zhukovsky

Sandgren

Silfverberg

et al. 2020

J Neurol Neurosurg Psychiatry

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“…Some of these alterations are attributed to the homeostatic proliferation of mature lymphocytes that the drug promotes in peripheral tissues [102]. Due to this effect, the administration of alemtuzumab has been linked with an increased susceptibility towards autoimmune comorbidities, such as autoimmune thyroid disease, membranous glomerulonephritis, autoimmune hepatitis, and immune thrombocytopenic purpura [103]. Colitis due to Clostridium was the cause of fatal outcome in one patient with RRMS who received alemtuzumab [104], whereas another patient presented with pancolitis during the first course of alemtuzumab treatment [105].…”

Section: Alemtuzumabmentioning

confidence: 99%

Microbiome in Multiple Sclerosis: Where Are We, What We Know and Do Not Know

et al. 2020

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An increase of multiple sclerosis (MS) incidence has been reported during the last decade, and this may be connected to environmental factors. This review article aims to encapsulate the current advances targeting the study of the gut–brain axis, which mediates the communication between the central nervous system and the gut microbiome. Clinical data arising from many research studies, which have assessed the effects of administered disease-modifying treatments in MS patients to the gut microbiome, are also recapitulated.

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“…With respect to the latter, subcutaneous treatment with alemtuzumab can lead to intracranial hemorrhage and secondary autoimmunity, as well as several other severe and fatal conditions. 39…”

Section: Discussionmentioning

confidence: 99%

CNS delivery of anti-CD52 antibodies modestly reduces disease severity in an animal model for multiple sclerosis

Bogie

Grajchen

Wouters

et al. 2020

Therapeutic Advances in Chronic Disease

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Background and aims: Alemtuzumab is a humanized monoclonal antibody that depletes CD52-bearing B and T lymphocytes. Clinical trials defined that systemic administration of alemtuzumab reduces disease severity in the relapsing–remitting phase of multiple sclerosis (MS). However, its efficacy in progressive MS patients is limited, which may reflect the inability of alemtuzumab to cross the reconstituted BBB in these patients. Objective: to study whether central nervous system (CNS) delivery of anti-CD52 antibodies reduces disease severity and the neuroinflammatory burden in the experimental autoimmune encephalomyelitis (EAE) model. Methods: Anti-CD52 antibodies were administered intrathecally during the acute and chronic phases of EAE. Flow cytometry and immunohistochemistry were utilized to define immunological and pathological parameters. Results: We show that subcutaneously administrated anti-CD52 antibodies completely abolish EAE disease severity. CNS delivery of anti-CD52 antibodies during both the acute and chronic phases of EAE moderately reduces disease severity and the neuroinflammatory burden. Our findings further suggest that CNS delivery of anti-CD52 antibodies impacts both the peripheral and CNS immune cell compartments in the EAE model but not in healthy mice. Conclusion: Collectively, our findings highlight the therapeutic potential of CNS delivery of alemtuzumab for the treatment of progressive as well as early MS.

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Adverse events with fatal outcome associated with alemtuzumab treatment in multiple sclerosis

Cited by 37 publications

References 17 publications

Autologous haematopoietic stem cell transplantation compared with alemtuzumab for relapsing–remitting multiple sclerosis: an observational study

Autologous haematopoietic stem cell transplantation compared with alemtuzumab for relapsing–remitting multiple sclerosis: an observational study

Microbiome in Multiple Sclerosis: Where Are We, What We Know and Do Not Know

CNS delivery of anti-CD52 antibodies modestly reduces disease severity in an animal model for multiple sclerosis

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