The Polyneuropathy And Treatment with Hizentra (PATH) study required subjects with chronic inflammatory demyelinating polyneuropathy (CIDP) to show dependency on immunoglobulin G (IgG) and then be restabilized on IgG before being randomized to placebo or one of two doses of subcutaneous immunoglobulin (SCIG). Nineteen of the 51 subjects (37%) randomized to placebo did not relapse over the next 24 weeks. This article explores the reasons for this effect. A post-hoc analysis of the PATH placebo group was undertaken. A literature search identified other placebo-controlled CIDP trials for review and comparison. In PATH, subjects randomized to placebo who did not relapse were significantly older, had more severe disease, and took longer to deteriorate in the IgG dependency period compared with those who relapsed. Published trials in CIDP, whose primary endpoint was stability or deterioration, had a mean non-deterioration (placebo effect) of 43%, while trials with a primary endpoint of improvement had a placebo response of only 11%. Placebo is an important variable in the design of CIDP trials. Trials designed to show clinical improvement will have a significantly lower effect of this phenomenon than those designed to show stability or deterioration.
Bibliographical noteFunding Information:
We thank all investigators and the subjects for participating in the PATH study. Individual participant data will not be shared. We also wish to thank Dr Luana Colloca for her helpful advice and encouragement during preparation of this manuscript. Editorial support, funded by CSL Behring, was provided by Meridian HealthComms Ltd. CSL Behring funded the PATH study and together with a steering committee was responsible for the design of the trial, data analysis, interpretation, and writing of this report. All authors critically reviewed results and gave approval to submit this report for publication.