Effect of Alemtuzumab Infusions on Vital Signs

Abstract 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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Post-operative vital signs: How often is too often?

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.30_suppl.210 ◽

2018 ◽

Vol 36 (30_suppl) ◽

pp. 210-210

Author(s):

Kristen Filson ◽

Colleen Atherholt ◽

Meredith Simoes ◽

Michael DiPalma ◽

Susheela John ◽

...

Keyword(s):

Vital Sign ◽

Best Practice ◽

Vital Signs ◽

Time Frame ◽

Evidence Based ◽

Background Current ◽

Safe Patient Care ◽

Published Evidence ◽

Blood Pressures ◽

Operative Monitoring

210 Background: Current protocol for post-operative patients admitted to medical-surgical/telemetry units from post anesthesia care units states vital signs are taken every 15 minutes for 1 hour, every 30 minutes for 2 hours and then, every 4 hours for 24 hours. To date, published evidence-based research regarding the frequency and duration of vital signs to safely monitor post-operative patients is limited. The goal is to determine best practice in post-operative vital sign monitoring to ensure safe patient care. The purpose of this review is to determine what frequency and duration of vital signs is required to identify a deviation greater than 20% of patient baseline to ensure safe post-operative monitoring of patients. Methods: A total of 742 post-operative patients’ charts were evaluated. A time frame in which vital signs deviated greater than 20% from patient baseline was established from the data collected. A chart was created depicting these results; listing the total deviations by individual vital sign and time frame. Results: Results show blood pressure and heart rate are the vital signs that have the greatest deviation from baseline followed by pulse-oximetry. Temperature deviations are widespread, while changes in respiratory rate are seen within the first hour. When looking at specific percentages, it was noted that 65% of the total patients reviewed had a 20% deviation from their baseline vital signs. Blood pressures made up 50% of those deviations, while heart rates made up 45%. A total of 27% of the deviations occurred 4-8 hours after admission, 13% of deviations occurred 8-12 hours after admission, 9% of deviations occurred 1.5 hours after admission, and 7% of deviations occurred 12-16 hours after admission. Conclusions: Based on these results, the best times to take post-operative vitals to ensure deviations are detected are: every 15 minutes for 30 minutes upon admission, 1.5 hours after admission, 4 hours after admission, and then every 4 hours for 20 hours. Findings indicate vital signs can safely be taken less frequently in post-operative patients admitted to medical-surgical/telemetry units.

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Mitoxantrone treatment in patients with early relapsing-remitting multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458507077621 ◽

2007 ◽

Vol 13 (8) ◽

pp. 975-980 ◽

Cited By ~ 19

Author(s):

E. Cocco ◽

P. Marchi ◽

C. Sardu ◽

P. Russo ◽

A. Paolillo ◽

...

Keyword(s):

Multiple Sclerosis ◽

Adverse Events ◽

Relapse Rate ◽

Serious Adverse Events ◽

T2 Lesions ◽

End Of Treatment ◽

Relapsing Remitting ◽

Annualized Relapse Rate ◽

Relapsing Remitting Multiple Sclerosis

We investigated the clinical and MRI effects of mitoxantrone (MITOX) administered to 45 patients during the first five years of highly active relapsing-remitting multiple sclerosis. Differences occurring between the end of treatment and follow-up (clinical mean: 3.6 years; brain MR: 1.8 years) with respect to baseline variables (EDSS, annualized relapse rate, active T2 lesions, new T1 lesions and number of Gd-enhancing lesions) were analysed using parametric and non-parametric tests. One patient developed leukemia four months after the end of the treatment; no other serious adverse events occurred during treatment and the follow-up period. A clinically relevant reduction in the annualized relapse rate ( P < 0.0001 at end of treatment and P < 0.0001 at follow-up) and improvement in the EDSS ( P < 0.0001 at end of treatment and P = 0.0005 at follow-up) was found. At the end of treatment, 53% of patients experienced no increase in active T2 lesions, while 73% showed no increase in the number of new T1 lesions. At follow-up, 41 out of 45 (91%) patients showed a stable MRI pattern and were active-scan free. Despite potential serious adverse events, MITOX may be considered an option in selected patients with very active early MS. Multiple Sclerosis 2007; 13: 975—980. http://msj.sagepub.com

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Sym001, the First Recombinant Polyclonal Rhesus-D Specific Antibody Product, Was Safe and Well-Tolerated in a Placebo-Controlled Randomized Phase I Trial.

Blood ◽

10.1182/blood.v112.11.1987.1987 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1987-1987

Author(s):

Peter Hjelmström ◽

Bengt Hallén ◽

Ewa Lindenstroem ◽

Shwe Gyaw

Keyword(s):

Clinical Chemistry ◽

Vital Signs ◽

Primary Objective ◽

Serious Adverse Events ◽

Laboratory Findings ◽

New Class ◽

Severe Intensity ◽

Clinically Significant ◽

To Receive ◽

Dose Dependent

Abstract Sym001 is the first compound in a new class of biopharmaceuticals in clinical development for the treatment of Immune Thrombocytopenic Purpura (ITP), and the prevention of hemolytic disease of the newborn by anti-D prophylaxis (ADP). Sym001 is a recombinant polyclonal antibody product consisting of 25 different anti-Rhesus D specific (RhD) antibodies. The primary objective of this clinical study was to assess the safety of Sym001 following a single intravenous (iv) dose in RhD+ and RhD− healthy male volunteers. Secondary objectives were to assess the potential immunogenicity and pharmacokinetic (PK) profile of Sym001. Fifty-nine RhD+ subjects and 18 RhD− subjects were randomized to receive up to 12.5 μg/kg or 75 μg/kg, respectively, in seven dose cohorts as shown below: Number of Subjects Cohort Dose (μg/kg) RhD+ Sym001 RhD+ Placebo RhD− Sym001 RhD− Placebo 1 0.25 5 2 0 0 2 1.0 5 2 0 0 3 4.0 7 2 7 2 4 12.5 7 2 7 2 5 25 7 2 0 0 6 50 7 2 0 0 7 75 7 2 0 0 Treatment with Sym001 was well tolerated and there were no serious adverse events (SAEs), no AEs of severe intensity and no AEs that resulted in discontinuation of the study in either the RhD+ or RhD− population. The frequencies of treatment-emergent AEs (TEAE), i.e. AEs occurring after drug administration, were similar among Sym001 and placebo treated subjects and there was no dose-dependent pattern of TEAEs. No significant decrease in mean hemoglobin level compared to baseline was observed at any dose level during the study, and no decrease in hemoglobin > 2 g/dL in any subject was seen. No other laboratory findings were suggestive of clinically significant hemolysis. In addition, no clinically significant changes in vital signs or electrocardiograms (ECGs) were observed, and there were no significant changes in clinical chemistry variables that did translate into SAEs or were assessed as being related to study medication. No immunogenicity to Sym001 was detected and analysis of PK is in progress. In conclusion, Sym001 was found to be safe and well-tolerated in healthy volunteers in doses up to 75 μg/ kg. Sym001 is now being evaluated in a red blood cell (RBC) challenge trial for the ADP indication and in a Phase II trial for treatment of patients with ITP.

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Natalizumab versus fingolimod in patients with relapsing-remitting multiple sclerosis non-responding to first-line injectable therapies

Multiple Sclerosis Journal ◽

10.1177/1352458516650736 ◽

2016 ◽

Vol 22 (10) ◽

pp. 1315-1326 ◽

Cited By ~ 40

Author(s):

Damiano Baroncini ◽

Angelo Ghezzi ◽

Pietro O Annovazzi ◽

Bruno Colombo ◽

Vittorio Martinelli ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Activity ◽

Brain Magnetic Resonance Imaging ◽

Lower Percentage ◽

First Line ◽

Serious Adverse Events ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Relapsing Remitting Multiple Sclerosis

Background: Natalizumab and fingolimod have not been compared in controlled trials but only in observational studies, with inconclusive results. Objectives: The objective of this study is to compare the effect of natalizumab and fingolimod in reducing disease activity in relapsing-remitting multiple sclerosis (RRMS). Methods: We included all consecutive RRMS patients switched from first-line agents (glatiramer acetate/interferons) to natalizumab or fingolimod, with a follow-up of 24 months. Data of relapses, Expanded Disability Status Scale score and brain magnetic resonance imaging (MRI) scans were collected. We used propensity score (PS) matching and intention-to-treat analysis. Results: We retained 102 patients in each cohort after PS matching, with similar baseline characteristics. More patients discontinued natalizumab compared to fingolimod (33% vs 11%, p < 0.001), mainly for progressive multifocal leukoencephalopathy (PML) concern. No serious adverse events occurred in the two cohorts. Compared to fingolimod, the natalizumab group presented a higher percentage of relapse-free patients (66% vs 80%, p = 0.015), a higher percentage of disability-improved patients (6% vs 15%, p = 0.033), a lower percentage of MRI-active patients (38% vs 14%, p = 0.001) and a higher percentage of patients with no evidence of disease activity (NEDA-3; 44% vs 70%, p < 0.001) after 2 years of follow-up. Disability worsening was not statistically different in the two groups. Conclusion: Natalizumab is superior to fingolimod in RRMS patients non-responding to first-line agents.

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