Incidence, management, and outcomes of autoimmune nephropathies following alemtuzumab treatment in patients with multiple sclerosis

Phelps, Richard G.; Winston, Jonathan; Wynn, Daniel; Habek, Mario; Hartung, Hans‐Peter; Havrdová, Eva; Markowitz, Glen S.; Margolin, David; Rodriguez, C. E.; Baker, Darren P.; Coles, Alasdair

doi:10.1177/1352458519841829

Cited by 30 publications

(44 citation statements)

References 38 publications

(68 reference statements)

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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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“…Three cases of ITP occurred in patients meeting the primary HAD definition in CARE-MS I, and none occurred in CARE-MS II [ 11 , 24 ]. One case of nephropathy in a patient meeting the primary HAD definition was reported in each of CARE-MS I and II [ 20 ]. Malignancies occurred in three CARE-MS I HAD patients and in no CARE-MS II HAD patients [ 11 , 15 , 25 ].…”

Section: Resultsmentioning

confidence: 99%

Efficacy and Safety of Alemtuzumab Through 9 Years of Follow-up in Patients with Highly Active Disease: Post Hoc Analysis of CARE-MS I and II Patients in the TOPAZ Extension Study

et al. 2020

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Background Alemtuzumab efficacy versus subcutaneous interferon-β-1a (SC IFNB-1a) was demonstrated over 2 years in patients with relapsing-remitting multiple sclerosis, with continued efficacy over 7 additional years. Alemtuzumab is included as a recommended treatment for patients with highly active disease (HAD) by the American Academy of Neurology Practice Guidelines, and the label indication in Europe was recently restricted to the treatment of HAD patients. There is currently no consensus definition for HAD, and alemtuzumab efficacy across various HAD definitions has not been explored previously. Objectives In this post hoc analysis, we assess the efficacy and safety of alemtuzumab in Comparison of Alemtuzumab and Rebif ® Efficacy in Multiple Sclerosis (CARE-MS) trial patients who met criteria for at least one of four separate definitions of HAD (one primary and three alternatives). Over 2 years, alemtuzumab-treated HAD patients were compared with SC IFNB-1a-treated HAD patients, with additional 7-year follow-up in patients from the alemtuzumab arm. Methods Patients in the CARE-MS studies received either alemtuzumab (baseline: 5 days; 12 months later: 3 days) or SC IFNB-1a (3 times weekly). Alemtuzumab-treated patients who enrolled in the extensions could receive additional courses ≥ 12 months apart. Four definitions of HAD were applied to assess alemtuzumab efficacy: the pre-specified primary definition (two or more relapses in the year prior to baseline and at least one gadolinium [Gd]-enhancing lesion at baseline) and three alternative definitions that focused on relapse, magnetic resonance imaging (MRI), or prior treatment response criteria. Efficacy outcomes were annualized relapse rate, change in Expanded Disability Status Scale score, 6-month confirmed disability worsening, 6-month confirmed disability improvement, MRI disease activity, and brain volume change. Adverse events were summarized for HAD patients meeting the primary definition. Results In the pooled CARE-MS population, 208 alemtuzumab-treated patients met the primary HAD definition. Annualized relapse rate was 0.27 in years 0-2 and 0.16 in years 3-9. Over 9 years, 62% of patients were free of 6-month confirmed disability worsening, 50% had 6-month confirmed disability improvement, and median cumulative change in brain volume was − 2.15%. During year 9, 62% had no evidence of disease activity, and 69% were free of MRI disease activity. Similar efficacy outcomes were observed using an alternative relapse-driven HAD definition. For patients meeting alternative HAD definitions focused on either higher MRI lesion counts or disease activity while on prior therapy, reduced efficacy for some endpoints was seen. Safety was consistent with the overall CARE-MS population through year 9. Conclusions Over 9 years, alemtuzumab efficacy was maintained in CARE-MS HAD patients based on four HAD definitions. These results support intervention with alemtuzumab in patients with early indicators of HAD, including frequent relapse without high MRI activity. No sa...

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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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Incidence, management, and outcomes of autoimmune nephropathies following alemtuzumab treatment in patients with multiple sclerosis

Cited by 30 publications

References 38 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

Efficacy and Safety of Alemtuzumab Through 9 Years of Follow-up in Patients with Highly Active Disease: Post Hoc Analysis of CARE-MS I and II Patients in the TOPAZ Extension Study

Effect of Alemtuzumab Infusions on Vital Signs

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