BOSTON – Subcutaneously administered immunoglobulin was effective, well tolerated, and preferred over intravenous administration as maintenance treatment for chronic inflammatory demyelinating polyneuropathy in the phase III, randomized, placebo-controlled PATH study.
The 172-patient trial tested a high and low dose of subcutaneous immunoglobulin (SCIg) over the course of 25 weeks to determine their effect on the primary outcome of chronic inflammatory demyelinating polyneuropathy (CIDP) relapse or withdrawal from treatment for any reason. In this evaluation of using SCIg for maintenance of response, relapses or treatment withdrawal occurred in 63% with placebo, 39% with low dose SCIg (0.2 g/kg weekly), and 33% with high dose (0.4 g/kg weekly), Ivo N. van Schaik, MD, reported at the annual meeting of the American Academy of Neurology.
Patients in the trial had received at lease one dose of intravenous immunoglobulin (IVIg) within 8 weeks before screening. They then underwent a screening period first, followed by an IgG dependency period of up to 12 weeks to test for ongoing need for IgG. The patients who experienced CIDP relapse during this test period were administered a standardized IVIG regimen during a 10- to 13-week restabilization period, and those who improved and maintained their Inflammatory Neuropathy Cause and Treatment (INCAT) score continued to the randomized subcutaneous treatment period of the study.
CIDP relapse occurred in 56% of patients in the placebo group, compared with 33% in the low- and 19% in the high-dose SCIg groups, said Dr. van Schaik of the University of Amsterdam (the Netherlands).
“Both [SCIg] doses were effective in preventing relapse. The higher dose performed better than the lower dose, but the difference was not statistically significant,” he said.
Both doses were significantly more effective than placebo.
Study participants were adults with definite or probable CIDP enrolled from 69 neuromuscular centers worldwide between March 2012 and November 2015. Weekly self-administered subcutaneous infusions of SCIg (IgPro20Hizentra) were performed during 1 or 2 consecutive days in two separate sessions using special infusion pumps. Patients reported that learning the self-administration technique was easy, Dr. van Schaik said.
Adverse effects included mainly local reactions, which occurred in 19% of patients, but these were generally mild and rarely resulted in therapy discontinuation, and local reactions decreased considerably over time, he said, noting that systemic effects are reduced with SCIg vs. IVIg.
Subcutaneous administration of immunoglobulin is not new. In fact, it has been used successfully in patients with immunodeficiency syndromes for more than 2 decades and can increase patient autonomy and reduce costs by reducing hospital and infusion center visits, but this is the first study to assess efficacy, safety, and tolerability of this approach in an adequately powered, randomized, clinical trial, he said.
“Subcutaneous immunoglobulin can be used ... for maintenance treatment of patients with CIDP,” he concluded, adding that weekly doses of 0.2-0.4 g/kg are supported by these data, and that maintenance doses should be individualized based on patient factors and previous IVIg dose and frequency.
The PATH study was sponsored by CSL-Behring. Dr. van Schaik chairs a steering committee for CSL-Behring and received departmental honoraria for serving on scientific advisory boards for CSL-Behring, Baxalta, and UCB. He also received speakers fees from CSL-Behring and Kedrion.