The Peripheral Nerve Society Annual Meeting was held in Miami in May 2022. The Foundation for Peripheral Neuropathy is pleased to be able to provide a summary of some of the clinical studies presented at the conference. Study teams reported on natural history studies and (clinical) intervention trials for Peripheral Neuropathies who concluded over the past year.
Natural History Study of SORD Neuropathy: Mutations in the sorbitol dehydrogenase (SORD) gene is a treatable cause of axonal neuropathy. This global observational study aims at reporting the full genotype-phenotype spectrum of SORD neuropathy and to define valid outcome parameters for future clinical trials. The team reported on the status of data analysis during the past year, which focused on the evaluation of changes in strength in different muscle groups. The average decrease in strength was 3% annually for muscles in the lower leg, such as ankle dorsi- and plantar flexion. Muscular strength declined by an average of 1% per year in more proximal muscle groups such as knee extension and flexion.
MRI Measured Dixon Fat Fraction is a Responsive Outcome Measure in CMT1X, CMT1B and CMT2A: Natural history study to search for outcome measures sensitive enough to detect decline in disease progression within a calendar year. It is important to find such sensitive outcomes because many agents proposed as potential treatments for different forms of CMT are believed to slow down disease progression, and not reverse symptoms. This study evaluated if fat fraction (% of fat in muscles) as determined by MRI in the leg, with measurement points at the mid-thigh and mid-calf demonstrates the required sensitivity. The study had a positive result, and confirmed that Fat Fraction in the leg muscles is a potential outcome measure for future intervention trials for CMT1X, CMT1B and CMT2A.
Predictors of Mobility, Balance, and Lower Extremity Function in Adult Charcot-Marie-Tooth Disease Type 1A: Working group is evaluating different standardized evaluations such as the 9-hole Peg Test, modified Stand-up and Go, 6-minute walk test and others as potential outcome measures for upcoming CMT1A trials. The group also evaluates the CMT-functional Outcome Measure (CMT-FOM) as a potential endpoint for intervention trials. Preliminary results were reported, confirming that proximal leg strength (thigh and hamstring muscles) maintains functionality and minimized balance issues. As a next step the working group plans to standardize the testing procedures for the different outcome measures validated for CMT.
Neuropathy Progression in ATTRv Patients After Orthotopic Liver Transplant: 69 patients participated in this study, which evaluated if the neuropathy symptoms progressed in patients with amyloidosis after patients received a liver transplant. In 57 patients, the neuropathy did not worsen, only 12 showed disease progression. All patients who demonstrated disease progression were older and had a higher than average polyneuropathy score prior to receiving a liver transplant. The effect of a new treatment using Patisiran and Inotersen in patients with disease progression was not known yet. The team is expected to report on those findings next year.
HELIOS-A: Impact of Vutrisiran on Quality of Life and Functional Status in Hereditary Transthyretin Mediated Amyloidosis: HELIOS-A study with patient with hATTR Amyloidosis. Patients treated with intravenous Patisiran 0.3 mg/kg every 3 weeks versus the new drug, subcutaneously administered Vutrisiran 25mg every 3 months. Patients receiving Vutrisiran showed positive outcome in comparison to patients who received Patisiran at two study endpoints at 9 and 18 months.
Topiramate as a Disease Modifying Therapy for Cryptogenic Sensory Peripheral Neuropathy (CSPN): a NeuroNEXT Trial: Topiramate as treatment of idiopathic neuropathy associated with metabolic syndrome. The medication is a sodium channel inhibitor and approved by the FDA to treat epilepsy and migraines. Participants needed to have HbA1c <7.5%, which is considered well controlled diabetes. Study endpoints were at 32, 64 and 96 weeks; the Norfolk Quality of Life-Diabetic Neuropathy (NQOL-DN) and Intraepidermal Nerve Fiber Density (IENFD) were the co-primary outcome measures for the trial. During run-in period (increasing dosage over time to recommended dosage), more patients were unable to tolerate drug compared to placebo. While there was no treatment benefit in the intent to treat analysis, there was a significant improvement in NQOL-DN in the treatment group when participants who were non-compliant based on serum topiramate levels were excluded (the per protocol analysis). While there was not a statistically significant difference in IENFD in the per protocol analysis, IENFD did not change in the treatment group, whereas it declined as anticipated in the placebo group. All secondary outcome measures (BMI, NCS, muscular strength, etc.) were negative. Further analysis of NQOL-DN subscales and other exploratory outcome measures is under way.
A double-blind, placebo-controlled Trial of IVIg in Patients with Small Fiber Neuropathy Associated with Autoantibodies to TS-HDS and FGFR3: Patients with Idiopathic Small Fiber Neuropathy associated with the TS-HDS and FGFR-3 autoantibodies were treated with IVIg or placebo: patients on active drug received 2 g/kg initial dosage followed by 1g/kg every 3 weeks for 24 weeks. Primary endpoint: IENFD, secondary: pain score, examination scores. Total of 44 patients were screened, 20 were randomized (10 active drug, 10 placebo). 8 active drug and 9 placebo users finished the study. Negative outcome for all primary and secondary outcome measures. This study clearly showed that IVIG does not have a therapeutic role even in patients with presumed autoimmune causes. Furthermore, this study shows that these antibodies may not be causative of SFN. The study author stated that “we can put these antibodies to rest.”
Rozanolixizumab in Chronic Inflammatory Demyelinating Polyradiculoneuropathy: Randomized Subject-/Investigator-Blind Placebo-Controlled Phase 2a Trial: Rozanolixizumab for treatment of CIDP, results from a Phase 2a study. Patient were treated with 10 mg/kg over 12 weeks or placebo, followed by a 12 week observation period. No differences between active drug and placebo for primary and secondary endpoints which included INCAT, iRODS or examination; 52% of placebo patients relapsed versus 50% of patients on Rozanolixizumab. Overall, trial had a negative outcome.
OPTIC Trial: Intravenous Immunoglobulin and Intravenous Methylprednisolone as Induction Treatment in CIPD – study update: Intravenous Immunoglobulin and Intravenous Methylprednisolone (IVIMP) as Induction Treatment in CIDP, investigating if the addition of Methylprednisolone has a positive effect on the efficacy of IVIg. Primary and secondary outcomes: remission after one year of treatment, INCST, iRODS. Intravenous Immunoglobulin 2g/kg with Intravenous Methylprednisolone 1g/kg for 18 weeks versus IVIg with placebo. Ongoing enrollment, no results yet.
Italian Database on Multifocal Motor Neuropathy: lesson from the first 100 included patients: 104 patients with multifocal motor neuropathy are enrolled to date, data analysis was done with 77 patient records; patients without NCS on file, and those with sensory or bulbar symptoms were excluded. 69% male, median age 41 (21-65), median disease duration 10 (0.3-35) years, ONLS score median 3 (0-9). Upper extremities nerves were more frequently affected than lower limb nerves, however majority of patients (69%) had weakness in both upper and lower extremities. Only IVIg or SCIg and cyclophosphaminde consistently improved MMN.
Target Therapies: Towards a Tailored Therapy in Anti-MAG Antibody Neuropathy with Ibrutinib, Venetoclax and Obinutuzumab: Ibrutinib, Venetoclax and Obinutuzumab as potential treatments for anti-MAG PN. 60 patients (39 men); 70% had MYD88 mutation. 65.7% of patients treated with on course of rituximab showed improvement.
Guillain-Barré Syndrome after COVID-19 vaccination: Review of health records in the United Kingdom documented that there was no increased risk of Guillain-Barré Syndrome (GBS) from the RNA-based vaccines such as Pfizer/Biontech or Moderna. However, there was a small increase in incidence of GBS after the first short of the Astra Zeneca vaccine (same type of vaccine as the Johnson & Johnson vaccine in the US). There was no increase in GBS occurrences after the second Astra Zeneca vaccination.