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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).
Mult Scler Relat Disord. 2019 Apr; 29:7-14.MS

Abstract

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 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.

METHODS

Patients were treated with a study regimen of enhanced IAR prophylaxis relative to phase 2 and 3 studies. H1 and/or H2 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.

Authors+Show Affiliations

Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, Hôpital Neurologique Pierre Wertheimer, Université 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.CRC-SEP, Pole des Neurosciences CHU Toulouse and UMR 1043, Université de Toulouse III, Toulouse, France.Clinical Investigation Center (CIC 1434), Strasbourg University Hospital, UMR 1119 and FMTS, Strasbourg, France.Department of Neurology, Hospital Universitario Virgen Macarena, Doctor Fedriani Avenue 3, 41009 Seville, Spain.Formerly of Department of Neurology, CUB-Hôpital Erasme, Route de Lennik 808, 1070 Brussels, Belgium; Sanofi, 50 Binney Street, 02142 Cambridge, Massachusetts, United States.Department of Neurology, Maasstad Ziekenhuis, Maasstadweg 21 3079 DZ Rotterdam, KvK 24299846, The Netherlands.Department of Neurology, AZ Sint Jan Brugge Oostende, Ruddershove 10, 8000, Brugge, Belgium.Sanofi, Torre Diagonal Mar, Calle Josep Pla, 2., 08019 Barcelona, Spain.Sanofi, 1 Avenue Pierre Brossolette 91385, Chilly-Mazarin, France; Experis Health, Immeuble Eureka, 13 Rue Ernest Renan, 92723 Nanterre, France.Sanofi, 1 Avenue Pierre Brossolette 91385, Chilly-Mazarin, France; Experis Health, Immeuble Eureka, 13 Rue Ernest Renan, 92723 Nanterre, France.Department of Neurology, Hospital Clínico San Carlos, IdISSC, Departamento de Medicina, Universidad Complutense de Madrid (UCM), Madrid, Spain.

Pub Type(s)

Clinical Trial, Phase IV
Journal Article
Multicenter Study

Language

eng

PubMed ID

30654246

Citation

Vukusic, Sandra, et al. "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)." Multiple Sclerosis and Related Disorders, vol. 29, 2019, pp. 7-14.
Vukusic S, Brassat D, de Seze J, et al. 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). Mult Scler Relat Disord. 2019;29:7-14.
Vukusic, S., Brassat, D., de Seze, J., Izquierdo, G., Lysandropoulos, A., Moll, W., Vanopdenbosch, L., Arque, M. J., Kertous, M., Rufi, P., & Oreja-Guevara, C. (2019). 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). Multiple Sclerosis and Related Disorders, 29, 7-14. https://doi.org/10.1016/j.msard.2019.01.019
Vukusic S, et al. 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). Mult Scler Relat Disord. 2019;29:7-14. PubMed PMID: 30654246.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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). AU - Vukusic,Sandra, AU - Brassat,David, AU - de Seze,Jerome, AU - Izquierdo,Guillermo, AU - Lysandropoulos,Andreas, AU - Moll,Wibe, AU - Vanopdenbosch,Ludo, AU - Arque,Maria Jesus, AU - Kertous,Mehdi, AU - Rufi,Pascal, AU - Oreja-Guevara,Celia, Y1 - 2019/01/06/ PY - 2018/07/06/received PY - 2019/01/03/revised PY - 2019/01/04/accepted PY - 2019/1/18/pubmed PY - 2019/7/17/medline PY - 2019/1/18/entrez KW - Alemtuzumab KW - Induction therapy KW - Infusion-associated reaction (IAR) KW - Methylprednisolone treatment KW - Multiple sclerosis KW - Rash SP - 7 EP - 14 JF - Multiple sclerosis and related disorders JO - Mult Scler Relat Disord VL - 29 N2 - 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 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. METHODS: Patients were treated with a study regimen of enhanced IAR prophylaxis relative to phase 2 and 3 studies. H1 and/or H2 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. SN - 2211-0356 UR - https://www.unboundmedicine.com/medline/citation/30654246/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__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2211-0348(19)30019-7 DB - PRIME DP - Unbound Medicine ER -