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

Ingemar S J Merkies ,Ivo N Van Schaik,Vera Bril,Claudia Sommer,Nan Van Geloven,Mika Saarela,Jerzy Kamienowski,Richard A Lewis,David R Cornblath,Billie L Durn,Jean‐Marc Léger,Wim Robberecht,John‐Philip Lawo,Orell Mielke,Gen Sobue,Björn Tackenberg,Hans‐Peter Hartung,Z Stelmasiak ,Jan De Bleecker

doi:10.1111/jns.12302

Abstract

Intravenous immunoglobulin (IVIG) is a potential therapy for chronic inflammatory demyelinating polyneuropathy (CIDP). To investigate the efficacy and safety of the IVIG IgPro10 (Privigen) for treatment of CIDP, results from Privigen Impact on Mobility and Autonomy (PRIMA), a prospective, open‐label, single‐arm study of IVIG in immunoglobulin (Ig)‐naïve or IVIG pre‐treated subjects (NCT01184846, n = 28) and Polyneuropathy And Treatment with Hizentra (PATH), a double‐blind, randomized study including an open‐label, single‐arm IVIG phase in IVIG pre‐treated subjects (NCT01545076, IVIG restabilization phase n = 207) were analyzed separately and together (n = 235). Efficacy assessments included change in adjusted inflammatory neuropathy cause and treatment (INCAT) score, grip strength and Medical Research Council (MRC) sum score. Adverse drug reactions (ADRs) and ADRs/infusion were recorded. Adjusted INCAT response rate was 60.7% in all PRIMA subjects at Week 25 (76.9% in IVIG pre‐treated subjects) and 72.9% in PATH. In the pooled cohort (n = 235), INCAT response rate was 71.5%; median time to INCAT improvement was 4.3 weeks. No clear demographic differences were noticed between early (responding before Week 7, n = 148) and late responders (n = 21). In the pooled cohort, median change from baseline to last observation was −1.0 (interquartile range −2.0; 0.0) point for INCAT score; +8.0 (0.0; 20.0) kPa for maximum grip strength; +3.0 (1.0; 7.0) points for MRC sum score. In the pooled cohort, 271 ADRs were reported in 105 subjects (44.7%), a rate of 0.144 ADRs per infusion. This analysis confirms the efficacy and safety of IgPro10, a recently FDA‐approved IVIG for CIDP, in a population of mainly pre‐treated subjects with CIDP [Correction added on 14 March 2019 after first online publication: the INCAT response rate has been corrected.].

Highlights

Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterized by symmetrical, proximal, and distal weakness or somatosensory alterations in the arms and legs that worsens over time.[1,2] The annual incidence of CIDP is estimated to be between 0.5 and 1.6 cases per 100 000 individuals and peak prevalence is between 40 and 60 years of age, with rates ranging from 1.6 to 8.9 per 100 000 adults in different regions.[3,4,5,6,7,8] CIDP occurs more commonly in men than women.[1]The goals of CIDP treatment are to reduce symptoms, improve functional ability, prevent relapse, and maintain long-term remission
Combination of the data originating from the Privigen Impact on Mobility and Autonomy (PRIMA) and Polyneuropathy And Treatment with Hizentra (PATH) studies resulted in the confirmation of the efficacy of IgPro[10] based on changes seen in adjusted inflammatory neuropathy cause and treatment (INCAT) score, grip strength, and Medical Research Council (MRC) sum score.[13,14]
A total of 89% of the responders in PRIMA and 99% of the responders in PATH responded by Week 10 based on INCAT score

Summary

| INTRODUCTION

Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterized by symmetrical, proximal, and distal weakness or somatosensory alterations in the arms and legs that worsens over time.[1,2] The annual incidence of CIDP is estimated to be between 0.5 and 1.6 cases per 100 000 individuals and peak prevalence is between 40 and 60 years of age, with rates ranging from 1.6 to 8.9 per 100 000 adults in different regions.[3,4,5,6,7,8] CIDP occurs more commonly in men than women.[1]. Results from the PRIMA and PATH studies are combined, aiming to determine whether the findings in the smaller PRIMA study would be validated by the much larger PATH trial, with the final objective to confirm the efficacy and safety of IgPro[10] for the treatment in a much larger group of patients with CIDP. The value of this combined analysis is that it leverages similarities in study design between the two studies, for example, same dosing paradigm and endpoints, to analyze the efficacy of IVIG in a large, combined patient cohort

| METHODS AND MATERIALS

| RESULTS

90 Improvement

Findings

| DISCUSSION