Immune thrombocytopenia in alemtuzumab-treated MS patients: Incidence, detection, and management

Cuker, Adam; Bass, Ann D; Nadj, Congor; Agius, Mark; Steingo, Brian; Selmaj, Krzysztof; Thoits, Timothy; Guerreiro, Alexandre; Wijmeersch, Bart Van; Ziemssen, Tjalf; Meuth, Sven G.; LaGanke, Christopher; Thangavelu, Karthinathan; Rodriguez, C. E.; Baker, Darren P.; Margolin, David; Jannsens, Ann

doi:10.1177/1352458518816612

Cited by 41 publications

(33 citation statements)

References 31 publications

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“…11 Throughout the alemtuzumab clinical development program for MS (up to 12 years, depending on the study), ITP occurred in ~2% of patients, and the incidence of nephropathies was 0.34%. 14,15 In CARE-MS II, patient-reported outcome (PRO) measures were used to evaluate the impact of alemtuzumab on patients' health-related quality of life (HRQL). At 2 years, the alemtuzumab group showed statistically significant improvements compared with SC IFNB-1a on PRO scores.…”

Section: Impact Of Alemtuzumab On Health-related Quality Of Life Overmentioning

confidence: 99%

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Impact of alemtuzumab on health-related quality of life over 6 years in CARE-MS II trial extension patients with relapsing-remitting multiple sclerosis

et al. 2019

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Background: In CARE-MS II (Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis; NCT00548405), alemtuzumab (12 mg/day; baseline: 5 days; 12 months later: 3 days) significantly improved health-related quality of life (HRQL) outcomes versus subcutaneous interferon beta-1a (SC IFNB-1a) in relapsing-remitting multiple sclerosis (RRMS) patients over 2 years. Patients completing CARE-MS II could enter a 4-year extension study (NCT00930553). Objective: The aim of this study is to assess 6-year HRQL outcomes in alemtuzumab-treated CARE-MS II patients, including those with highly active disease (HAD). Methods: During extension, patients could receive additional alemtuzumab for clinical/magnetic resonance imaging (MRI) activity or other disease-modifying therapies per investigator’s discretion. Assessments include Functional Assessment of Multiple Sclerosis (FAMS), 36-Item Short-Form Health Survey (SF-36), and EQ-5D visual analog scale (EQ-VAS). Results: Alemtuzumab-treated patients improved or stabilized all HRQL measures over 6 years with significant improvements from baseline at all time points on EQ-VAS and for up to 5 years on FAMS, SF-36 MCS, and SF-36 PCS. Alemtuzumab-treated patients with HAD showed significant improvements versus baseline at Year 2 on all HRQL measures, and significant improvements versus SC IFNB-1a on SF-36 PCS and EQ-VAS; however, the improvements did not reach the threshold for clinical relevance. Conclusion: Alemtuzumab-treated CARE-MS II patients improved or stabilized HRQL versus baseline over 6 years. This is the first study to show long-term HRQL benefits in patients with HAD.

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Section: Impact Of Alemtuzumab On Health-related Quality Of Life Overmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of alemtuzumab on health-related quality of life over 6 years in CARE-MS II trial extension patients with relapsing-remitting multiple sclerosis

et al. 2019

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“…Immune-mediated thrombocytopenia occurs in approximately 2% of MS patients treated with alemtuzumab [21]. It usually responds well to standard treatment with corticosteroids, although the fatal case reported here indicates that this is not always the case.…”

Section: Discussionmentioning

confidence: 79%

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

et al. 2019

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Objective Sporadic fatal adverse events have been reported during treatment of multiple sclerosis with alemtuzumab. To provide a systematic overview, we searched the centralized European Medicines Agency database of suspected adverse reactions related to medicinal products (EudraVigilance) for fatal adverse events associated with treatment with alemtuzumab (Lemtrada®) for multiple sclerosis. Four independent reviewers with expertise on MS, clinical immunology, infectious diseases and clinical pharmacology reviewed the reports, and scored the likelihood for causality. Results We identified nine cases with a probable and one case with a possible causal relationship between alemtuzumab treatment and a fatal adverse event. Six of these patients died within one month after treatment; one from intracerebral hemorrhage, two from acute multiple organ failure and septic shock, one from listeriosis, one from pneumonia and one from agranulocytosis. Four patients died several months after administration of alemtuzumab from either autoimmune hepatitis, immune-mediated thrombocytopenia, autoimmune hemolytic anemia or agranulocytosis. Four of the 10 cases had been published previously in case reports or congress abstracts. Fatal adverse events related to treatment with alemtuzumab occur more frequently than previously published in the literature. A significant proportion occurs in the first month after treatment.

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“…2 and 3 core and extension trials, respectively, patients most commonly developed thyroid events (42%) and, less frequently, immune thrombocytopenia (2.2%) and nephropathies (0.34%) over a median of 6.1 years of follow-up after the first infusion. [14][15][16] A monitoring program has been used to detect and manage these AEs to minimize the associated risks. 17 Limitations of the study revolve around its observational design.…”

Section: Practice Pointsmentioning

confidence: 99%

Effect of Alemtuzumab Infusions on Vital Signs

Chinea¹,

Honeycutt²,

Miller³

et al. 2020

International Journal of MS Care

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Background: Alemtuzumab efficacy and safety were established in phase 3 randomized trials. We characterize vital signs during and after the first alemtuzumab infusion course. Methods: Patients with relapsing-remitting multiple sclerosis commercially prescribed alemtuzumab 12 mg/day on 5 consecutive days (initial course) were enrolled in this prospective, observational study. Preinfusion medications included methylprednisolone, antihistamine, and antipyretics. Primary end point: change from precourse baseline in vital signs during and 2 hours after each alemtuzumab infusion. Secondary end points: infusion duration and serious adverse events (AEs) starting within 24 hours and within 7 days after infusion (AEs collected up to 15 days after treatment). Potentially clinically significant vital sign abnormalities were based on predefined thresholds from literature review. Results: In the 304 patients treated, minimal increases in mean systolic (≤8 mm Hg) and diastolic (≤3 mm Hg) blood pressures from precourse baseline were observed on infusion days 3 to 5. An increase in mean heart rate (20 beats per minute) during the first infusion day normalized by day 2, and smaller increases (5 beats per minute) occurred during subsequent infusions. Serious AEs occurred in two patients (0.7%) during or within 24 hours after infusion and in three patients (1.0%) within 7 days. Mean/median infusion duration was 4 hours. Vital sign abnormalities with potential clinical significance occurred in 62.5% of patients. Conclusions: Although most patients had potentially clinically significant vital sign abnormalities, mean changes from baseline during and after infusion of the first alemtuzumab course were clinically insignificant. No new safety signals were detected.

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Immune thrombocytopenia in alemtuzumab-treated MS patients: Incidence, detection, and management

Cited by 41 publications

References 31 publications

Impact of alemtuzumab on health-related quality of life over 6 years in CARE-MS II trial extension patients with relapsing-remitting multiple sclerosis

Impact of alemtuzumab on health-related quality of life over 6 years in CARE-MS II trial extension patients with relapsing-remitting multiple sclerosis

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

Effect of Alemtuzumab Infusions on Vital Signs

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