Analysis of relapse by inflammatory Rasch-built overall disability scale status in the PATH study of subcutaneous immunoglobulin in chronic inflammatory demyelinating polyneuropathy

Clinical trials in chronic inflammatory demyelinating polyneuropathy (CIDP) often assess efficacy using the ordinal Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. Here, data from the PATH study was reanalyzed using change in Inflammatory Rasch-built Overall Disability Scale (I-RODS) to define CIDP relapse instead of INCAT. The PATH study comprised an intravenous immunoglobulin (IVIG) dependency period and an IVIG (IgPro10 [Privigen]) restabilization period; subjects were then randomized to weekly maintenance subcutaneous immunoglobulin (SCIG; IgPro20 [Hizentra]) 0.2 g/kg or 0.4 g/kg or placebo for 24 weeks. CIDP relapse was defined as >= 1-point deterioration in adjusted INCAT, with a primary endpoint of relapse or withdrawal rates. This retrospective exploratory analysis redefined relapse using I-RODS via three different cut-off methods: an individual variability method, fixed cut-off of >= 8-point deterioration on I-RODS centile score or >= 4-point deterioration on I-RODS raw score. Relapse or withdrawal rates were 47% for placebo, 34% for 0.2 g/kg IgPro20 and 19% for 0.4 g/kg IgPro20 using the raw score; 40%, 28% and 15%, respectively using the centile score, and 49%, 40% and 27%, respectively using the individual variability method. IgPro20 was shown to be efficacious as a maintenance therapy for CIDP when relapse was defined using I-RODS. A stable response pattern was shown for I-RODS across various applied cut-offs, which could be applied in future clinical trials

Analysis of relapse by inflammatory Rasch-built overall disability scale status in the PATH study of subcutaneous immunoglobulin in chronic inflammatory demyelinating polyneuropathy

Clinical trials in chronic inflammatory demyelinating polyneuropathy (CIDP) often assess efficacy using the ordinal Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. Here, data from the PATH study was reanalyzed using change in Inflammatory Rasch‐built Overall Disability Scale (I‐RODS) to define CIDP relapse instead of INCAT. The PATH study comprised an intravenous immunoglobulin (IVIG) dependency period and an IVIG (IgPro10 [Privigen]) restabilization period; subjects were then randomized to weekly maintenance subcutaneous immunoglobulin (SCIG; IgPro20 [Hizentra]) 0.2 g/kg or 0.4 g/kg or placebo for 24 weeks. CIDP relapse was defined as ≥1‐point deterioration in adjusted INCAT, with a primary endpoint of relapse or withdrawal rates. This retrospective exploratory analysis redefined relapse using I‐RODS via three different cut‐off methods: an individual variability method, fixed cut‐off of ≥8‐point deterioration on I‐RODS centile score or ≥4‐point deterioration on I‐RODS raw score. Relapse or withdrawal rates were 47% for placebo, 34% for 0.2 g/kg IgPro20 and 19% for 0.4 g/kg IgPro20 using the raw score; 40%, 28% and 15%, respectively using the centile score, and 49%, 40% and 27%, respectively using the individual variability method. IgPro20 was shown to be efficacious as a maintenance therapy for CIDP when relapse was defined using I‐RODS. A stable response pattern was shown for I‐RODS across various applied cut‐offs, which could be applied in future clinical trials

Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (The PATH Study): study protocol for a randomized controlled trial

Subcutaneous administration of Ig (SCIg) has gained popularity as an alternative route of administration but has never been rigorously examined in chronic inflammatory demyelinating polyneuropathy (CIDP). The primary objective of the PATH study (Polyneuropathy and Treatment with Hizentra) is to determine the efficacy of two different doses of SCIg IgPro20 (0.2 g/kg bw or 0.4 g/kg bw) in a 24-week maintenance treatment of CIDP in comparison to placebo. The primary efficacy endpoint will be the proportion of patients who show CIDP relapse (1-point deterioration on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score) or are withdrawn within 24 weeks after randomization for any reason. IVIg-dependent adult patients with definite or probable CIDP according to the European Federation of Neurological Societies/Peripheral Nerve Society who fulfil the inclusion and exclusion criteria will be eligible. Based on sample-size calculation and relapse assumptions in the three arms, a sample size of 58 is needed per arm (overall sample size will be 350, of which 174 will be randomized). All eligible patients will progress through three study periods: an IgG dependency period (≤12 weeks) to select those who are Ig dependent; an IVIg restabilization period (10 or 13 weeks), which will be performed using the 10 % IgPro10 product; and an SC treatment period (24 weeks, followed by a 1-week completion visit after last follow-up). Patients showing IVIg restabilization will be randomized to demonstrate the efficacy of SCIg IgPro20 maintenance treatment over placebo. After completing the study, subjects are eligible to enter a long-term, open-label, extension study of 1 year or return to their previous treatment. In case of CIDP relapse during the 24-week SC treatment period, IgPro10 rescue medication will be offered. Safety, tolerability, and patients' preference of Ig administration route will be examined. The PATH trial, which started in March 2012, is expected to finish at the end of 2016. The results will increase knowledge about the efficacy, safety, and tolerability of SCIg in maintenance management of CIDP patients. ClinicalTrials.gov, NCT01545076 . Registered on 1 March 201

INTRAVENOUS IMMUNOGLOBULIN (IVIG) FOR RESTABILIZATION TREATMENT AFTER IVIG WITHDRAWAL IN CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY (CIDP). RESULTS FROM THE PRE-RANDOMIZATION PHASE OF THE PATH STUDY

Development and application of statistical models for medical scientific researc

Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (CIDP), a multicenter randomized double-blind placebo-controlled trial: The PATH Study

Development and application of statistical models for medical scientific researc

RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO INVESTIGATE THE EFFICACY, SAFETY AND TOLERABILITY OF TWO DIFFERENT DOSES OF IGPRO20 (SUBCUTANEOUS IMMUNOGLOBULIN) FOR THE TREATMENT OF CIDP: IGG DEPENDENCY AND RESTABILIZATION PHASE

Development and application of statistical models for medical scientific researc

SUBCUTANEOUS IMMUNOGLOBULIN FOR MAINTENANCE TREATMENT IN CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY - A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL: THE PATH STUDY

Development and application of statistical models for medical scientific researc

SUBCUTANEOUS IMMUNOGLOBULIN FOR MAINTENANCE TREATMENT IN CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY (CIDP), A MULTICENTER RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL: THE PATH STUDY

Development and application of statistical models for medical scientific researc