PMID- 30654246 OWN - NLM STAT- MEDLINE DCOM- 20190716 LR - 20191210 IS - 2211-0356 (Electronic) IS - 2211-0348 (Linking) VI - 29 DP - 2019 Apr TI - 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). PG - 7-14 LID - S2211-0348(19)30019-7 [pii] LID - 10.1016/j.msard.2019.01.019 [doi] AB - BACKGROUND: 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 IFNbeta-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. METHODS: Patients were treated with a study regimen of enhanced IAR prophylaxis relative to phase 2 and 3 studies. H(1) and/or H(2) 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. RESULTS: 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. CONCLUSION: 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. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Vukusic, Sandra AU - Vukusic S AD - Service de Neurologie, Sclerose en Plaques, Pathologies de la Myeline et Neuro-Inflammation, Hopital Neurologique Pierre Wertheimer, Universite Claude Bernard Lyon 1, Hospices Civils de Lyon, and Centre de Recherche en Neurosciences de Lyon - INSERM 1028 et CNRS UMR5292, 59 boulevard Pinel 69677 BRON cedex, Lyon, France. Electronic address: sandra.vukusic@chu-lyon.fr. FAU - Brassat, David AU - Brassat D AD - CRC-SEP, Pole des Neurosciences CHU Toulouse and UMR 1043, Universite de Toulouse III, Toulouse, France. FAU - de Seze, Jerome AU - de Seze J AD - Clinical Investigation Center (CIC 1434), Strasbourg University Hospital, UMR 1119 and FMTS, Strasbourg, France. FAU - Izquierdo, Guillermo AU - Izquierdo G AD - Department of Neurology, Hospital Universitario Virgen Macarena, Doctor Fedriani Avenue 3, 41009 Seville, Spain. FAU - Lysandropoulos, Andreas AU - Lysandropoulos A AD - Formerly of Department of Neurology, CUB-Hopital Erasme, Route de Lennik 808, 1070 Brussels, Belgium; Sanofi, 50 Binney Street, 02142 Cambridge, Massachusetts, United States. FAU - Moll, Wibe AU - Moll W AD - Department of Neurology, Maasstad Ziekenhuis, Maasstadweg 21 3079 DZ Rotterdam, KvK 24299846, The Netherlands. FAU - Vanopdenbosch, Ludo AU - Vanopdenbosch L AD - Department of Neurology, AZ Sint Jan Brugge Oostende, Ruddershove 10, 8000, Brugge, Belgium. FAU - Arque, Maria Jesus AU - Arque MJ AD - Sanofi, Torre Diagonal Mar, Calle Josep Pla, 2., 08019 Barcelona, Spain. FAU - Kertous, Mehdi AU - Kertous M AD - Sanofi, 1 Avenue Pierre Brossolette 91385, Chilly-Mazarin, France; Experis Health, Immeuble Eureka, 13 Rue Ernest Renan, 92723 Nanterre, France. FAU - Rufi, Pascal AU - Rufi P AD - Sanofi, 1 Avenue Pierre Brossolette 91385, Chilly-Mazarin, France; Experis Health, Immeuble Eureka, 13 Rue Ernest Renan, 92723 Nanterre, France. FAU - Oreja-Guevara, Celia AU - Oreja-Guevara C AD - Department of Neurology, Hospital Clinico San Carlos, IdISSC, Departamento de Medicina, Universidad Complutense de Madrid (UCM), Madrid, Spain. LA - eng PT - Clinical Trial, Phase IV PT - Journal Article PT - Multicenter Study DEP - 20190106 PL - Netherlands TA - Mult Scler Relat Disord JT - Multiple sclerosis and related disorders JID - 101580247 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antipyretics) RN - 0 (Histamine Antagonists) RN - 0 (Immunologic Factors) RN - 0 (Proton Pump Inhibitors) RN - 3A189DH42V (Alemtuzumab) RN - X4W7ZR7023 (Methylprednisolone) SB - IM MH - Adult MH - Alemtuzumab/administration & dosage/*adverse effects MH - Anti-Inflammatory Agents/administration & dosage/*pharmacology MH - Antibodies, Monoclonal, Humanized/administration & dosage/*adverse effects MH - Antipyretics/pharmacology MH - Drug Therapy, Combination MH - *Drug-Related Side Effects and Adverse Reactions/drug therapy/epidemiology/etiology/prevention & control MH - *Exanthema/chemically induced/drug therapy/epidemiology/prevention & control MH - Female MH - Histamine Antagonists/pharmacology MH - Humans MH - Immunologic Factors/administration & dosage/*adverse effects MH - Incidence MH - Infusions, Intravenous/*adverse effects MH - Male MH - Methylprednisolone/administration & dosage/*pharmacology MH - Middle Aged MH - Multiple Sclerosis, Relapsing-Remitting/*drug therapy MH - *Outcome Assessment, Health Care MH - Proton Pump Inhibitors/pharmacology OTO - NOTNLM OT - Alemtuzumab OT - Induction therapy OT - Infusion-associated reaction (IAR) OT - Methylprednisolone treatment OT - Multiple sclerosis OT - Rash EDAT- 2019/01/18 06:00 MHDA- 2019/07/17 06:00 CRDT- 2019/01/18 06:00 PHST- 2018/07/06 00:00 [received] PHST- 2019/01/03 00:00 [revised] PHST- 2019/01/04 00:00 [accepted] PHST- 2019/01/18 06:00 [pubmed] PHST- 2019/07/17 06:00 [medline] PHST- 2019/01/18 06:00 [entrez] AID - S2211-0348(19)30019-7 [pii] AID - 10.1016/j.msard.2019.01.019 [doi] PST - ppublish SO - Mult Scler Relat Disord. 2019 Apr;29:7-14. doi: 10.1016/j.msard.2019.01.019. Epub 2019 Jan 6.