Fingolimod Does Not Slow Worsening of Chronic Inflammatory Demyelinating Polyradiculoneuropathy
The trial was ended for futility when a total of 44 worsening events had occurred in the cohort.
In a double-blind randomized controlled trial published in Lancet Neurology, fingolimod, an immunomodulating therapy commonly used for treating relapsing-remitting multiple sclerosis, was not superior to placebo in reducing clinically confirmed worsening of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).
Patients with CIDP who were receiving corticosteroids or intravenous immunoglobulin (IVIg) therapy at 48 neurology centers in Australia were randomly assigned to receive either once-daily 0.5 mg oral fingolimod (n=54) or placebo (n=52). During a 45-day screening period, patients were allowed to continue on corticosteroids or IVIg; IVIg treatment was discontinued the day before starting the randomly assigned therapy and corticosteroids were gradually discontinued over 8 weeks after randomization. Time to first confirmed disease worsening, defined as a ≥1-point increase on the adjusted Inflammatory Neuropathy Cause and Treatment disability scale score, comprised the primary trial end point.
The trial was ended for futility when a total of 44 worsening events had occurred in the cohort. The percentage of patients who were free of confirmed disease worsening was similar in the group assigned to fingolimod (42% [95% CI, 23-60]) and the placebo group (43% [95% CI, 28-59]) (P =.91). A higher percentage of patients receiving placebo experienced adverse events (85% vs 76%); however, patients who received fingolimod experienced a greater number of serious adverse events than patients receiving placebo (17% vs 8%, respectively). Headache (22%), hypertension (19%), and extremity pain (13%) were the most common adverse events reported in the fingolimod arm. Study discontinuation related to therapy was 13% and 0% in the fingolimod and placebo arms, respectively.
A limitation of the analysis was the inclusion of previously treated patients with CIDP, which may reduce generalizability of the findings across treatment-naïve patients.
Considering that some patients with CIDP do not fully respond “…to corticosteroids, IVIg, or plasma exchange or have intolerable side-effects with them, [so] the search for alternative treatment options or add-on treatments should continue.”
Hughes R, Dalakas MC, Merkies I, et al. Oral fingolimod for chronic inflammatory demyelinating polyradiculoneuropathy (FORCIDP Trial): a double-blind, multicentre, randomised controlled trial. Lancet Neurol. 2018;17(8):689-698.