Intravenous immunoglobulin for maintenance treatment of chronic inflammatory demyelinating polyneuropathy: a multicentre, open-label, 52-week phase III trial

Abstract

Objective: Short-term efficacy of induction therapy with intravenous immunoglobulin (Ig) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) is well established. However, data of previous studies on maintenance therapy were limited up to 24-week treatment period. We aimed to investigate the efficacy and safety of longer-term intravenous Ig therapy for 52 weeks.

Methods: This study was an open-label phase 3 clinical trial conducted in 49 Japanese tertiary centres. 49 patients with CIDP who fulfilled diagnostic criteria were included. After an induction intravenous Ig therapy (0.4 g/kg/day for five consecutive days), maintenance dose intravenous Ig (1.0 g/kg) was given every 3 weeks for up to 52 weeks. The primary outcome measures were the responder rate at week 28 and relapse rate at week 52. The response and relapse were defined with the adjusted Inflammatory Neuropathy Cause and Treatment scale.

Results: At week 28, the responder rate was 77.6% (38/49 patients; 95% CI 63% to 88%), and the 38 responders continued the maintenance therapy. At week 52, 4 of the 38 (10.5%) had a relapse (95% CI 3% to 25%). During 52 weeks, 34 (69.4%) of the 49 enrolled patients had a maintained improvement. Adverse events were reported in 94% of the patients; two patients (66-year-old and 76-year-old men with hypertension or diabetes) developed cerebral infarction (lacunar infarct with good recovery), and the other adverse effects were mild and resolved by the end of the study period.

Conclusions: Maintenance treatment with 1.0 g/kg intravenous Ig every 3 weeks is an efficacious therapy for patients with CIDP, and approximately 70% of them had a sustained remission for 52 weeks. Thrombotic complications should be carefully monitored, particularly in elderly patients with vascular risk factors.

Trial registration number: ClinicalTrials.gov (NCT01824251).

Conflict of interest statement

Competing interests: SKuw, SKus, GS, and RK have received consultancy fees, lecture fees and travel expenses on the steering committee from Nihon Pharmaceutical. KSa is employees of Nihon Pharmaceutical. All other authors declare that they have no conflict of interest.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1

Study design and trial profile. INCAT, Inflammatory Neuropathy Cause and Treatment.

Figure 2

Responder rate and relapse rate. The responder rate is defined as the percentage of patients who had sustained INCAT score improvement of 1 point or more compared with that at week 1 (before administration) at week 28. The relapse rate indicates the percentage of patients whose INCAT score fell by 1 point or more from that of week 28 (before administration) at week 52. Horizontal lines indicate the responder rate (20.7%) for placebo group in the ICE study first period and relapse rate (42.3%) for placebo group in ICE study extension phase. ICE, Intravenous Ig in CIDP Efficacy; INCAT, Inflammatory Neuropathy Cause and Treatment.

Figure 3

Transition diagram for the total INCAT score (A) and MRC sum score (B). INCAT, Inflammatory Neuropathy Cause and Treatment; MRC, Medical Research Council; SCR, screening.