IqYmune® is an effective maintenance treatment for multifocal motor neuropathy: A randomised, double‐blind, multi‐center cross‐over non‐inferiority study vs Kiovig®—The LIME Study

Abstract

Intravenous immunoglobulin (IVIg) is the gold‐standard for maintenance treatment of multifocal motor neuropathy (MMN). This phase III, randomised, double‐blind, multi‐centre, active‐control, crossover study, aimed to evaluate the non‐inferiority of IqYmune® relative to Kiovig®, primarily based on efficacy criteria. Twenty‐two adult MMN patients, treated with any brand of IVIg (except Kiovig® or IqYmune®) at a stable maintenance dose within the range of 1 to 2 g/kg every 4 to 8 weeks, were randomised to receive either Kiovig® followed by IqYmune®, or IqYmune® followed by Kiovig®. Each product was administered for 24 weeks. The primary endpoint was the difference between IqYmune® and Kiovig® in mean assessments of modified Medical Research Council (MMRC) 10 sum score (strength of 5 upper‐limb and 5 lower‐limb muscle groups, on both sides, giving a score from 0 to 100) during the evaluation period (non‐inferiority margin of Δ = 2). A linear mixed model analysis demonstrated the non‐inferiority of IqYmune® relative to Kiovig®, independently of the covariates (value at baseline, treatment period, and treatment sequence). The estimated “IqYmune® − Kiovig®” difference was −0.01, with a 95% confidence interval (CI) −0.51 to 0.48. The number of adverse reactions (ARs) and the percentage of patients affected were similar for the two products: 39 ARs in 10 patients with IqYmune® vs 32 ARs in 11 patients with Kiovig®. No thromboembolic events nor haemolysis nor renal impairment were observed. In this first clinical trial comparing two IVIg brands for maintenance treatment of MMN, efficacy and tolerability of both brands were similar.

Incidence and risk factors for intravenous immunoglobulin‐related hemolysis: A systematic review of clinical trial and real‐world populations

“…18,24 Only a few hemolytic events have been reported when products produced by Cohn fractionation, ethanol-PEG, and ethanol-OA plus IAC were given. 22,27 This suggests an association between an increased risk of hemolysis with increased amounts of isoagglutinins administered to the patient. However, further analyses to investigate this relationship and the impact of patient risk factors, like blood group, are required.…”

“…Furthermore, no hemolysis cases were observed in clinical trials that used IVIG products produced by Cohn fractionation or ethanol‐OA fractionation followed by IAC isoagglutinin reduction. However, cases were observed in IVIG products that used ethanol‐OA‐purified products 22,25,29 …”

“…Patients treated with IVIG were between 3 and 82 years old and 64% were male (sex breakdown detailed in seven of the eight clinical trials [22][23][24][25][27][28][29] ). Reported conditions being treated by IVIG in these clinical trials included ITP (three studies 23,24,26 ), with other studies including patients with CIDP, 29 MMN, 22 or myasthenia gravis (MG). 28 Two studies included patients with primary immunodeficiencies treated with IVIG.…”

“…From the eight clinical trials included, patient sample size ranged from 22 to 102 patients (Table 1). Patients treated with IVIG were between 3 and 82 years old and 64% were male (sex breakdown detailed in seven of the eight clinical trials [22][23][24][25][27][28][29] ). Reported conditions being treated by IVIG in these clinical trials included ITP (three studies 23,24,26 ), with other studies including patients with CIDP, 29 MMN, 22 or myasthenia gravis (MG).…”

An international multicenter efficacy and safety study of IqYmune in initial and maintenance treatment of patients with chronic inflammatory demyelinating polyradiculoneuropathy: PRISM study

“…IqYmune (I10E for code product) is a highly purified, ready‐to‐use, 10% liquid preparation of normal human immunoglobulin (100 mg/mL) for intravenous administration. This formulation is obtained from thousands of healthy donors and has been shown to be effective and well tolerated in patients with primary immunodeficiency 5 (PID), multifocal motor neuropathy 6 (MMN), and primary immune thrombocytopenia (ITP) 7 …”