Intravenous immunoglobulin (IVIG) is safe and effective as maintenance therapy for patients with chronic inflammatory demyelinating polyneuropathy (CIDP) when administered at 1.0 g/kg, according to a double-blind, randomized, parallel-group, phase 3 study presented at the American Association of Neuromuscular & Electrodiagnostic Medicine 2020 Virtual Annual Meeting.
The findings also highlighted a potential dose-dependent response to IVIG maintenance treatment.
The research team randomized 142 patients with probable or definite CIDP 1:2:1 to receive 0.5 g/kg, 1.0 g/kg, or 2.0 g/kg IVIG, respectively, as maintenance therapy every three weeks for up to 24 weeks.
"In general, IVIG has been studied in the clinical setting, which involves an induction dose of 2.0 g/kg followed by 1.0 g/kg dosing every three weeks," said the lead study author David Cornblath, MD, professor of neurology at the Johns Hopkins University School of Medicine in Baltimore.
"What the [current] ProCID study did that was unique was to systematically study a higher maintenance dose of 2.0 g/kg every three weeks and a lower maintenance dose of 0.5 g/kg every three weeks. So that provided us with an opportunity to evaluate a dose-response."
The response rate in the 1.0 g/kg cohort—indicated by a decrease of at least one point in the adjusted Inflammatory Neuropathy Cause and Treatment Disability (INCAT) score from baseline to week 24—was met among 79.7 percent of responders in the intention-to-treat group, the researchers found.
Treatment response seemed to be dose-dependent, reflected by the increased proportions of responders as measured by the adjusted INCAT score as the doses rose: 64.7 percent, 79.7 percent, and 91.7 percent, respectively, in the 0.5, 1.0 and 2.0 g/kg dose cohorts, the authors noted.
Other outcome measures such as grip strength, muscle strength, social participation and activity limitations also suggested a dose-dependent response with a higher proportion of responders in the 2.0 g/kg cohort compared to the 1.0 and 5.0 g/kg maintenance therapy doses.
"We have confirmed, which theoretically is no surprise to anybody, that 1.0g/kg as a maintenance dose following the induction dose works for people previously diagnosed with CIDP who were taken off their current medication," Dr. Cornblath said.
Dr. Cornblath added that the current study and others have shown that even with the induction dose, about half the people will improve by a single point on the INCAT scale, which is easily measured and is considered to be an objective measure of improvement.
"For neurologists, it's very helpful to begin to make the INCAT exam part of the standard examination in patients with CIDP," he said.
Corticosteroids, IVIG, and plasma exchange are three approved therapies for CIDP, noted Dr. Cornblath. "In our study, the study patients were mainly on corticosteroids, and then restarted on IVIG," Dr. Cornblath noted.
"We don't yet know whether there's a statistical dose-response that might change therapy," Dr. Cornblath told Neurology Today. "We are in the process of analyzing that data."
"Based on the findings of this study, neurologists may consider escalating the dose of IVIG from 1 to 2 g/kg in patients that do not improve on the lower dose," said Norman Latov, MD, PhD, professor of neurology and director of the Peripheral Neuropathy Center at Weill Cornell Medical Center in NY. "Such patients are currently considered treatment failures, but they might respond to higher doses," said Dr. Latov, who was not involved in the study.
"Current protocols recommend maintenance on 1 g/kg every three weeks, based on a pivotal single-dose trial," Dr. Latov noted, "but higher doses were not tested, and further analysis indicated ongoing demyelinating activity, even in patients that appeared to be clinically stable."
This investigation also raises the question of whether some patients with a limited response may be under-treated; in these instances, increasing the dose may provide greater improvement, Dr. Latov noted.
"Most studies measure the rate of response, but we also need to assess the magnitude of improvement, ongoing demyelinating activity, and rate of subsequent relapses. There is a need for research into more sensitive markers of disease activity to help guide treatment decisions," he added.
These findings support our current clinical practice of administering 1 g/kg IVIG as maintenance therapy in CIDP every three weeks, added Eva L. Feldman, MD, PhD, FAAN, the Russell N. DeJong Professor of Neurology and director of NeuroNetwork for Emerging Therapies at the University of Michigan. "The data confirm our clinical 'suspicion' and practice: that IVIG is dose-dependent and a lower dose is less effective, while a higher dose is more effective."
This study provides us with the evidence we need to practice evidence-based medicine, Dr. Feldman told Neurology Today.
Dr. Cornblath disclosed relationships with Mitsubishi Tanabe Pharma Corporation, Alnylam Pharmaceuticals, Inc, Hansa Medical AB, PledPharma, Momenta Pharmaceuticals, Inc.Consultant for CSL Behring, Sanofi-Aventis Recherche & Development, INC, Seattle Genetics, Octapharma AG, Grifols, S.A., Cigna Corporation, Pharnext SA, Annexon Biosciences, UCB Pharma Inc., Boehringer Ingelheim Therapeutics, Biotest Pharmaceuticals, Inc., Argenx, CytomX Therapeutics, PassageBio Pharma, and financial interests with Genentech Corp, Merrimack Pharmaceuticals, Disarm Therapeutics, Inc, Levicept Ltd., Amgen Inc., and Syntimmune, Inc. (sold to Alexion Pharma). Dr. Latov disclosed relationships with Polyneuron Pharmaceuticals, Therapath LLC, Cornell University, and Takeda. Dr. Feldman did not report any disclosures.
Link Up for More Information:
AANEM 2020 Abstract 3: Cornblath D, Van Doorn P, Hartung HP, et al. The ProCID Study: Efficacy and safety of 3 different dosages of IVIG (Panzyga) in patients with chronic inflammatory demyelinating polyneuropathy.