“Placebo response” refers to an unexpected improvement with placebo and is an important variable in clinical trial design. However, in CIDP trials, it can refer to the absence of expected clinical deterioration with placebo. Here, placebo response rates from the PATH study of subcutaneous immunoglobulin (SCIG) as maintenance therapy for CIDP are compared with studies in CIDP and other neurological conditions.

To compare placebo response from the PATH study with other studies in chronic inflammatory demyelinating polyneuropathy (CIDP) and intravenous immunoglobulin (IVIG) therapy. 

In the PATH study, IVIG was withdrawn from IVIG-dependent subjects in an immunoglobulin (IgG) dependency period. Any clinical deterioration was restabilized with IVIG (1 g/kg; IgPro10, Privigen®) over 10–13 weeks; subjects were then randomized to weekly SCIG (0.2 or 0.4 g/kg; IgPro20, Hizentra®) or placebo for 24 weeks. Primary endpoint was CIDP relapse (≥1 point increase in total adjusted Inflammatory Neuropathy Cause and Treatment [INCAT] score) or withdrawal. Placebo responses in other studies were identified by a PubMed search of randomized controlled trials. 

In the IgG dependency period, 28/245 (11.4%) subjects did not deteriorate (10 discontinued for other reasons). Of the 207 subjects who entered the IVIG restabilization period, 172 demonstrating CIDP stability were randomized to placebo, SCIG 0.2 or 0.4 g/kg (n=57;57;58). In the placebo group, 37% did not relapse/withdraw, compared with 61% and 67% for SCIG. Placebo-controlled CIDP trials in the literature reported placebo response or non-relapse rates of 10–55%, using a range of outcomes (e.g., Medical Research Council sum score, INCAT) and treatments (e.g., IVIG, methotrexate).

The PATH study has important implications for clinical practice and CIDP trials, highlighting placebo effect and the remitting-relapsing nature of CIDP as efficacy confounders. Comparisons with other studies question the reasons for this and whether study design can mitigate these effects.