Single-arm study to assess comprehensive infusion guidance for the prevention and management of the infusion associated reactions (IARs) in relapsing-remitting multiple sclerosis (RRMS) patients treated with alemtuzumab (EMERALD).

Single-arm study to assess comprehensive infusion guidance for the prevention and management of the infusion associated reactions (IARs) in relapsing-remitting multiple sclerosis (RRMS) patients treated with alemtuzumab (EMERALD).

Publication date: Apr 01, 2019

Alemtuzumab is a humanized IgG monoclonal antibody approved in more than 60 countries for patients with relapsing remitting multiple sclerosis (RRMS). In phase 2 and 3 clinical trials (CAMMS223 (NCT00050778), CARE-MS I (NCT00530348), and CARE-MS II (NCT00548405)), patients receiving alemtuzumab demonstrated significantly greater improvements on clinical and MRI outcomes versus SC IFNβ-1a; mild to moderate infusion-associated reactions (IARs) were the most frequently reported adverse events (AEs) associated with alemtuzumab. EMERALD (NCT02205489) was a phase 4, multicenter, multinational, single-arm study designed to assess an algorithm for the prevention and management of IARs in RRMS patients treated with alemtuzumab.

Patients were treated with a study regimen of enhanced IAR prophylaxis relative to phase 2 and 3 studies. H and/or H antagonists or equivalent gastroprotection (proton pump inhibitors) were given 1 day before alemtuzumab infusion, 1 h prior to the infusion, and post-infusion. Methylprednisolone was given orally 1 day before infusion, 1 h prior to the infusion, and as needed post-infusion. Antipyretics were given 1 h before infusion and as needed post-infusion. Anti-emetics and normal saline were given as needed during and post-infusion.

Of the 61 patients screened, 58 (95.1%) were enrolled into the study. Of the 58 patients who received the first infusion of Period 1, 57 (98.3%) completed the 5 days of Course 1. A total of 54 patients received the first infusion of Period 2 and 53 completed the 3-day course. All patients (n = 58) completed the Month 6 visit and 54 the Month 12 visit. 93.1% of patients had at least one IAR (91.4% in Period 1 and 81.5% in Period 2), the majority of which were grade 1 (69.1%) or grade 2 (28.0%). The three most common IARs of headache, pyrexia, and rash occurred in 48.8%, 40.7%, and 24.1% of patients during the first course and 14.8%, 17.2%, and 5.6% of patients during the second course, respectively. The majority of IARs occurred within 6 h after the start of alemtuzumab infusion, with a peak during the first 2 h. The types and overall incidence of IARs were consistent with phase 2 and 3 trials. Frequency and distribution of rash were reduced in the EMERALD study compared with previous clinical trials. Serious IARs occurred in 15.5%, a higher rate than reported in clinical trials of alemtuzumab.

Although most alemtuzumab-treated patients experienced IARs as in previous controlled clinical studies, there was an improvement in the frequency and distribution of alemtuzumab-associated rash, which may have been associated with this study’s prophylaxis regimen.

Vukusic, S., Brassat, D., de Seze, J., Izquierdo, G., Lysandropoulos, A., Moll, W., Vanopdenbosch, L., Arque, M.J., Kertous, M., Rufi, P., and Oreja-Guevara, C. Single-arm study to assess comprehensive infusion guidance for the prevention and management of the infusion associated reactions (IARs) in relapsing-remitting multiple sclerosis (RRMS) patients treated with alemtuzumab (EMERALD). 17636. 2019 Mult Scler Relat Disord (29):

Concepts Keywords
Alemtuzumab MRI
Algorithm Monoclonal antibodies
CARE ICE
Clinical Trials 1H
Emetics Organ systems
Frequency Cytokine release syndrome
Headache Immunology
IgG Multiple sclerosis
Incidence Medical specialties
Infusion Sanofi
Methylprednisolone Alemtuzumab
Monoclonal Antibody Rash study
MRI MS
Multinational
Multiple Sclerosis
Normal Saline
Peak
Prophylaxis
Proton Pump Inhibitors
Pyrexia
Rash

Semantics

Type Source Name
disease DOID Multiple sclerosis
disease MESH Multiple sclerosis
disease DOID rash
drug DRUGBANK Methylprednisolone
gene UNIPROT SLC35G1
gene UNIPROT PTPRN2
gene UNIPROT AES
gene UNIPROT CYREN
drug DRUGBANK Alemtuzumab
disease DOID relapsing-remitting multiple sclerosis
disease MESH relapsing-remitting multiple sclerosis
gene UNIPROT IARS
gene UNIPROT ARMC9
gene UNIPROT AKR1A1

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