A double-blind, placebo controlled trial of Gamunex-C in Patient with Small Fiber Neuropathy Associated with Autoantibodies to TS-HDS and FGFR3

ABSTRACT

Objective: To determine the efficacy of IVIG on nerve fiber density, pain and examination scores in a double blind placebo controlled pilot study of patients with SFN associated with TS-HDS and FGFR3. Background: Small fiber neuropathies (SFN) have many potential causes but >50% remain idiopathic. Two autoantibodies, TS-HDS and FGFR-3, are associated with ∼20% of idiopathic SFN cases with reports touting IVIG for treatment of presumed autoimmune SFN. Design/Methods: Twenty subjects with SFN confirmed by history, examination and skin biopsy with elevated autoantibodies to TS-HDS and/or FGFR3 received either IVIG (or blinded placebo) dosed at 2 grams/kg followed by 1 gram/kg every 3 weeks for a total of 6 treatments. All subjects had detailed small fiber examinations (UENS), questionnaires and skin biopsies taken from adjacent sites at the distal leg. Skin biopsies were stained for PGP9.5 and intra-epidermal nerve fiber density (IENFD) reported. Final follow up occurred 3 weeks after the final treatment (24 weeks). Results: Twenty subjects were enrolled;18 completed treatment (9 IVIG, 9 placebo completers -2 did not have final data due to COVID-19). Over 24 weeks the change in pain scores (11 point VAS scale) was -0.88±0.99 in the placebo group, and -0.56±2.8 in the IVIG group (P=NS), the UENS neuropathy score improved by 3.8±8.8 in the placebo group and improved by 3.7±4.1 in the IVIG group (P=NS). Skin biopsy IENFD improved by 1.24±1.79 fibers/mm in the placebo group and improved by 0.81±1.67 fibers/mm in the IVIG treated group (P=NS). Conclusions: This small double blind placebo controlled trial showed no difference between IVIG and placebo in any measurable outcome and does not support the use of IVIG for SFN associated with autoantibodies to TS-HDS and/or FGFR3.