ECTRIMS: EMERALD Shows High Compliance Rate With Alemtuzumab

Interim analysis from the ongoing EMERALD [Evaluation of the Management of Infusion Reactions in Alemtuzumab- treated Patients] study will help provide additional guidance for optimizing the management of infusion-associated reactions (IARs) that occur during the administration of alemtuzumab in patients with relapsingremitting multiple sclerosis.

Most patients receiving alemtuzumab in MS clinical trials experienced mild or moderate IARs during infusion (most commonly headache, rash, pyrexia, and nausea). The findings were presented in a poster at the ECTRIMS meeting. EMERALD is a phase 4, single-arm, multinational, open-label study in patients with RRMS initiating alemetzumab. Duration is approximately 13.5 months over 2 study periods, corresponding with 2 alemtuzumab treatment courses. Patients received intravenous (IV) alemtuzumab 12 mg/day on 5 consecutive days (Period 1) and on 3 consecutive days 12 months later (Period 2).

Pre-infusion medication was administered the day before each period (H1- and H2-antagonists and oral methylprednisolone). On day 1 of each period, premedication was given 1 hour before infusion (H1- and H2-antagonists, nonsteroidal anti-inflammatory drug [NSAID]/ antipyretic, and IV methylprednisolone). Subsequent infusion days followed a similar premedication regimen, but with decreasing methylprednisolone until day 5 (Period 1) or day 3 (Period 2).

During and after infusion, as-needed symptomatic medications could be administered including antihistamine, antipyretic, saline, antiemetic, and/or proton pump inhibitor.

All patients received H1- and H2-antagonists after infusion. The primary end point was to assess the distribution of IARs by severity grade when alemtuzumab and infusionassociated medications are administered following comprehensive infusion guidance. The investigators defined IARs as any adverse event occurring during infusion, the 2-hour period after infusion, and up to 24 hours after infusion.

Compliance Implications

For the current analysis, the study’s aim was to report baseline patient characteristics and medication compliance during the initial course of alemtuzumab. The study enrolled 58 patients (mean age 36.4 years and 60% female) between November 2014 and February 2015. The mean time since diagnosis was 9.7 years, mean Expanded Disability Status Score was 4.1, and the mean number of relapses in the last year was 1.8. A majority of the patients (91%) had received prior MS therapy, most commonly natalizumab (55%), fingolimod (53%), glatiramer acetate (38%), and interferon beta-1a intramuscular (35%) or subcutaneous (31%).

During Period 1, 57 patients received the full course of 5 alemtuzumab infusions, 54 of whom had infusions on 5 consecutive days per protocol; 1 patient received 3 infusions on 3 consecutive days. The researchers found that the EMERALD study population had more advanced disease and previous exposure to more types of disease-modifying therapies than did patients in the alemtuzumab phase 2 and 3 studies. Compliance with mandatory premedication was high (100% for aciclovir or equivalent, H1-antagonist, methylprednisolone, and NSAID/antipyretic; 98% for H2-antagonist).

“In this interim analysis, EMERALD patients had a high rate of compliance with the alemtuzumab infusion schedule and premedication regimen, suggesting feasibility of this regimen in clinical practice,” concluded the researchers. Alemtuzumab, a humanized anti-CD52 monoclonal antibody, was FDA approved in November 2014 for the treatment of relapsing forms of MS.—Eileen Koutnik-Fotopoulos

This study was supported by funding from Genzyme, a Sanofi Company.