By Michael Rubin, MD
Professor of Clinical Neurology, Weill Cornell Medical College
Dr. Rubin reports he is a consultant for Merck Sharp & Dohme Corp.
SYNOPSIS: IqYmune is a highly purified 10% concentration of human immunoglobulin obtained from healthy volunteers. It appears to have similar efficacy in the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) as conventional intravenous immunoglobulin, with 76% of the study patients showing a significant improvement in a standardized disability score.
SOURCE: Nobile-Orazio E, Pujol S, Kasiborski F, et al. An international multicenter efficacy and safety study of IqYmune in initial and maintenance treatment of patients with chronic inflammatory demyelinating polyradiculoneuropathy: PRISM study. J Peripher Nerv Syst 2020; Aug. 18. doi.org/10.1111/jns.12408. [Online ahead of print].
Based on several studies, the largest of which is the double-blind, multicenter ICE (Intravenous immunoglobulin [IVIg] in chronic inflammatory demyelinating polyneuropathy [CIDP] Efficacy) trial in 2008, IVIg has become a first-line treatment for CIDP, preferred over steroids because IVIg provides a more rapid onset of clinical improvement and a better adverse effect profile. It also is preferred over plasma exchange because of the ease of use and availability of IVIg.1 Administered intravenously, IqYmune, a highly purified 10% liquid preparation of normal human immunoglobulin obtained from healthy donors and approved in Europe in 2015 as replacement therapy for primary immunodeficiency syndrome and hypogammaglobulinemia, has been used successfully to treat multifocal motor neuropathy and Guillain-Barré syndrome. Is it beneficial in CIDP?
In this prospective, international, multicenter, single-arm, open-label, Phase III study extending from February 2015 to September 2017, the efficacy and safety of IqYmune in CIDP was examined. Patients with CIDP, 18 years of age or older, diagnosed using the 2010 clinical and neurophysiological criteria of the European Federation of Neurological Societies/Peripheral Nerve Society guidelines, with a disability score of at least 2, were included. Also included were those with pure motor and pure sensory forms, and those with an associated monoclonal gammopathy of unknown significance. Exclusionary criteria comprised immunoglobulin allergy, immunoglobulin A (IgA) deficiency, hepatic disease, or any cardiovascular condition with increased thromboembolic risk. Prior immunomodulatory treatment within 12 months, or plasma exchange, steroids, or blood derivatives in the prior three months also were grounds for exclusion. IqYmune 2 g/kg was administered as an induction dose, followed by seven infusions of 1 g/kg every three weeks.
Inflammatory neuropathy cause and treatment (INCAT) disability score at study end (week 24) was the primary endpoint, with the placebo group of the ICE trial used as a historical control. Secondary endpoints included responder rate at week 12, time to initial response, and grip strength in both hands using the Martin Vigorimeter.
Among 59 patients screened for the study, only 44 met all criteria for enrollment. Of these, 23 were Ig-naïve, and 21 had relapsed following prior Ig treatment. In this latter group, one withdrew consent prior to treatment, and another was not assessed post-baseline. Among 42 patients remaining in the study and included in the efficacy set, having primary efficacy endpoint assessment availability, overall response rate at study end with an improvement of at least one point in the INCAT disability score was 76.2%, with IqYmune demonstrating superiority to historical placebo controls (P < 0.0001). Time to response varied from nine to 19 weeks, with a median time of 15 weeks. Adverse effects (AEs) were experienced by 90.7% of patients and believed to be related to IqYmune in 69.8%. Headaches, fever, and myalgias were the most common drug-related AEs, all of which resolved without sequelae, except for worsening of pre-existing anemia in a gastrectomy patient treated with B12. Nine serious AEs were seen in seven patients, five of which were related to IqYmune in three patients, including a transient ischemic attack in one patient (who was withdrawn prematurely); a severe headache leading to hospitalization, an anaphylactic reaction, and an increase in D-dimer, all in a second patient; and an asymptomatic neutropenia in a third patient. IqYmune appears safe and effective for CIDP.
COMMENTARY
IVIg also appears safe at higher infusion rates than usual. The standard infusion rate of 10% IVIg is 0.08 mL/kg/min. When incrementally increased to a maximum rate of 0.14 mL/kg/min in patients who tolerated the initial infusion rate, 19 of 25 patients in a prospective, open-label trial at the Ellen and Martin Prosserman Center for Neuromuscular Diseases, University Health Network, Toronto, Ontario, safely tolerated the increased rate. No treatment-related AEs were associated with the higher infusion rate. Increasing the infusion rate will reduce treatment time and reduce healthcare costs.2
REFERENCES
- Hughes RAC, Donofrio P, Bril V, et al. Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): A randomized placebo-controlled trial. Lancet Neurol 2008;7:136-144.
- Jiang Y, Mendoza M, Sarpong E, et al. Efficacy and safety of high infusion rate IVIG in CIDP. Muscle Nerve 2020; Aug. 12. doi: 10.1002/mus.27044. [Online ahead of print].