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

Abstract

ObjectiveShort-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.MethodsThis 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.ResultsAt 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.ConclusionsMaintenance 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 numberClinicalTrials.gov (NCT01824251).

Efficacy and safety of IVIG in CIDP: Combined data of the PRIMA and PATH studies

“…The response rate in treatment‐naïve subjects in the PRIMA study (46.7%) is in a similar range to the 55% INCAT response rate reported in treatment‐naïve subjects in the Cochrane review . A higher response rate was observed in pre‐treated subjects in our combined analysis; the Kuwabara et al study, where all subjects were IVIG pre‐treated, had a responder rate of 77.6% at Week 28 . It is also of note that in this combined analysis, there was a proportion of subjects who had previously responded to IVIG who did not respond well after the withdrawal (wash‐out) and re‐establishment of IVIG treatment.…”

“…This timing should be considered in clinical practice prior to deciding if a subject is not benefitting from treatment early in the treatment course. A recent study reported that 69% of subjects treated with IVIG for 52 weeks maintained INCAT improvement, further supporting the acute and long‐term use of IVIGs …”

“…Recently, a Japanese study (n = 49) also reported IVIG efficacy with long‐term treatment (induction IVIG 2 g/kg bodyweight [bw] over five consecutive days, maintenance IVIG 1.0 g/kg bw every 3 weeks for up to 52 weeks). The study reported a response rate of 78% at 28 weeks, with a 10.5% relapse rate within the population that continued treatment to Week 52 …”

A population‐based study of long‐term outcome in treated chronic inflammatory demyelinating polyneuropathy

“…Patients with chronic inflammatory demyelinating polyneuropathy (CIDP) can be treated with immune‐modulating therapy, including immunoglobulins, plasma exchange, and steroids. The therapeutic short‐term effect has been demonstrated in trials with a maximum duration of 1 to 2 years . The long‐term outcome of immune‐modulating treatment has been evaluated in hospital based follow‐up series or cross‐sectional studies.…”

Neurological autoimmune disorders with prominent gastrointestinal manifestations: A review of presentation, evaluation, and treatment

“…Dosing is typically based upon weight, with an initial dose of 2 g/kg administered over the course of 3‐5 days . As a maintenance strategy, it can be repeated every 2‐4 weeks, typically at a dose of 1 g/kg over 2‐3 days . Due to its significant cost and side effects, second‐line immunotherapy may be started simultaneously to try to reduce the frequency of needed IVIG infusions …”