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

Holmøy, Trygve; Fevang, Børre; Olsen, David B.; Spigset, Olav; Bø, Lars Eirik

doi:10.21203/rs.2.11268/v1

Cited by 6 publications

(6 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The aetiology of these events remains unknown, although it might revolve around elevated BP. One of the cases developed hypertension and cytokine storm and died 5 days after the first infusion due to ICH; autopsy revealed necrotizing vasculopathy [8]. Cytokine release syndrome is a systemic inflammatory response syndrome known to occur after alemtuzumab administration and may contribute to haemorrhagic stroke [8].…”

Section: Discussionmentioning

confidence: 99%

“…One of the cases developed hypertension and cytokine storm and died 5 days after the first infusion due to ICH; autopsy revealed necrotizing vasculopathy [8]. Cytokine release syndrome is a systemic inflammatory response syndrome known to occur after alemtuzumab administration and may contribute to haemorrhagic stroke [8]. Additionally, alemtuzumab increases pro‐inflammatory cytokines 24 h after administration, targeting CD16+ monocytes, which might be the rationale for increasing BP [9].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Blood pressure changes during alemtuzumab infusion for multiple sclerosis patients

Shosha

Casserly

Tomkinson

et al. 2020

Euro J of Neurology

View full text Add to dashboard Cite

Background and purpose Blood pressure (BP) changes during alemtuzumab infusions are poorly understood. The aim of this study was to examine BP changes during alemtuzumab infusions in persons with multiple sclerosis (PwMS). Methods This was a retrospective cohort review of systolic (S) and diastolic (D) BP in PwMS receiving alemtuzumab. Results Thirty‐one patients were identified; 22 (64.5%) were women. Mean age and disease duration were 35.2 ± 7.1 and 9.2 ± 5.4 years, respectively. There was no history of hypertension or vascular events. Mean baseline SBP was 119.8 ± 15.1 mmHg, 118.8 ± 14.3 mmHg and 106.5 ± 6.1 mmHg whilst mean DBP was 75.3 ± 9.2 mmHg, 74.1 ± 12.4 mmHg and 69.2 ± 4.3 mmHg at doses 1, 6 and 9, respectively. During the first cycle, SBP increased by 19.2 ± 9.4 mmHg, with comparable percentage increases over the five infusions (16%, 22%, 17%, 11%, 13%, respectively). DBP increased by 6.2 ± 3.8 mmHg with similar percentage increases over the five infusions (8.4%, 11.5%, 5.5%, 7%, 3%). For the second cycle, SBP increased by 16.9 ± 3.2 mmHg, with similar increases over the 3 days (12%, 15%, 17%). DBP increased by 5.4 ± 4.2 mmHg (11%, 9%, 12.8%). The third cycle demonstrated increased mean and percentage of SBP and DBP by 8.9 ± 2.3 mmHg (10%, 70%, 11.8%) and 4.2 ± 1.9 mmHg (3%, 2%, 6.5%), respectively. Collectively, for 31 patients, in the first cycle, mean SBP increased from 119.8 ± 15.1 mmHg to 138.8 ± 13 mmHg (p ˂ 0.001), whilst mean DBP increased from 74.5 ± 9.2 mmHg to 79.2 ± 9.1 mmHg (p = 0.007). Overall, 17 (54.8%) patients had increasing BP by ≥20% and nine (29%) had increasing BP by ≥20 mmHg from baseline. Conclusions This demonstrates significant increases in BP during alemtuzumab infusions in PwMS.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Blood pressure changes during alemtuzumab infusion for multiple sclerosis patients

Shosha

Casserly

Tomkinson

et al. 2020

Euro J of Neurology

View full text Add to dashboard Cite

show abstract

“…These cases have included opportunistic infections, such as listeriosis, cytomegalovirus infection, pulmonary aspergilosis, and cerebral or pulmonary nocardiosis; autoimmune cytopenias; autoimmune hepatitis; autoimmune hemolytic anemia; hemophagocytic lymphohistiocytosis; acute acalculous cholecystitis; and potentially infusion-related cardiovascular and pulmonary events. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] Patients who completed the CARE-MS core studies could enter a 4-year extension [CAMMS03409 (NCT00930553)]. Previous interim analyses have shown 5-and 6-year efficacy and safety in alemtuzumab-treated patients, but did not provide outcomes beyond year 2 in patients who were first randomized to SC IFNB-1a.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of alemtuzumab over 6 years: final results of the 4-year CARE-MS extension trial

Coles

Arnold

Bass

et al. 2021

Ther Adv Neurol Disord

View full text Add to dashboard Cite

Background: In the 2-year CARE-MS I and II trials, alemtuzumab 12 mg administered on 5 consecutive days at core study baseline and on 3 consecutive days 12 months later significantly improved outcomes versus subcutaneous interferon beta-1a (SC IFNB-1a) in relapsing–remitting multiple sclerosis patients. Here, we present the final 6-year CARE-MS extension trial results (CAMMS03409), and compare outcomes over 6 years in patients randomized to both treatment groups at core study baseline. Methods: Over a 4-year extension, alemtuzumab patients (alemtuzumab-only) received as-needed additional alemtuzumab (⩾12 months apart) for disease activity after course 2. SC IFNB-1a patients who entered the extension discontinued SC IFNB-1a and received 2 alemtuzumab 12 mg courses (IFN–alemtuzumab), followed by additional, as-needed, alemtuzumab. Results: Through year 6, 63% of CARE-MS I and 50% of CARE-MS II alemtuzumab-only patients received neither additional alemtuzumab nor other disease-modifying therapy, with lasting suppression of disease activity, improved disability, and slowing of brain volume loss (BVL). In CARE-MS I patients (treatment-naive; less disability; shorter disease duration), disease activity and BVL were significantly reduced in IFN–alemtuzumab patients, similar to alemtuzumab-only patients at year 6. Among CARE-MS II patients (inadequate response to prior treatment; more disability; longer disease duration), alemtuzumab significantly improved clinical and magnetic resonance imaging outcomes, including BVL, in IFN–alemtuzumab patients; however, disability outcomes were less favorable versus alemtuzumab-only patients. Safety profiles, including infections and autoimmunities, following alemtuzumab were similar between treatment groups. Conclusion: This study demonstrates the high efficacy of alemtuzumab over 6 years, with a similar safety profile between treatment groups. ClinicalTrials.gov identifiers: NCT00530348; NCT00548405; NCT00930553

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

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

Cited by 6 publications

References 9 publications

Blood pressure changes during alemtuzumab infusion for multiple sclerosis patients

Blood pressure changes during alemtuzumab infusion for multiple sclerosis patients

Efficacy and safety of alemtuzumab over 6 years: final results of the 4-year CARE-MS extension trial

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

Contact Info

Product

Resources

About