Post-hoc findings from the phase 3 TERIKIDS study (NCT02201108) of teriflunomide (Aubagio; Sanofi) in children with relapsing multiple sclerosis (MS) showed that treatment with a disease-modifying therapy significantly increased plasma neurofilament light (pNfL) levels. A biomarker of axonal injury.
TERIKIDS was a 96-week, multicenter, multinational, randomized, double-blind (DB), placebo-controlled, parallel-group study evaluating teriflunomide in pediatric relapsed MS followed by a 96-week A blinded extension (OLE) was performed. Despite similar least-squares mean pNfL levels observed at baseline, values were significantly lower in patients on teriflunomide vs. placebo for DB duration and his OLE duration combined (192 weeks: 10.61 vs. 17.32 pg/day) mL; P. <.01).
Principal Investigator Jens Kuhle, M.D., Chief Physician at Basel University Hospital and Director of the Center for Multiple Sclerosis, and colleagues said, Its usefulness needs further investigation.” training. “
From the original patient cohort, 111 (67%) individuals volunteered to participate in the substudy and had measurements available. This included her 33 patients in the placebo group and her 78 patients in the teriflunomide group. Plasma NfL was measured using a single-molecule Symore array immunoassay with a calibration range of 500–0.167 pg/ml. All samples were briefly centrifuged to sediment aggregates, and the cleared supernatant was diluted at least 4-fold with sample diluent, plated into 96-well microtiter plates, and processed on the Quanterix HD-X Analyzer. bottom.
Baseline demographic and disease characteristics were similar to the overall study population, with a median of 193 (interquartile range) follow-up patients in the substudy. [IQR], 191.1-196.1) weeks. In the DB period, his pNfL levels on placebo increased until his 24th week and decreased at 36th week. By this time, 10 of his 33 patients (30.3%) on placebo had an early transition compared to 12 of his 78 patients (15.4%) on teriflunomide. to OLE after experiencing recurrence or high MRI activity. Notably, week 24 of DB had the greatest intergroup difference in pNfL values, with a geometric least squares mean ratio (GLSMR) of 0.74 (95% CI, 0.53–1.05; P. = .09) Teriflunomide vs placebo.
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At 5 of 6 time points during OLE, pNfL values were significantly different between the two treatment arms, with GLSMR for teriflunomide/teriflunomide versus placebo/teriflunomide ranging from 0.61 to 0.65. In an exploratory analysis that included adjustment for the number of MRI lesions at 24 weeks DB, the GLSMR for teriflunomide vs. placebo at 24 weeks DB declined from 0.74 in the main analysis to 0.98 and 1.00. Each lesion is counted as a covariate.
After adjusting for gadolinium-enhancing lesions at DB week 24 and the number of new/enlarged T2 lesions, the investigators observed a decline in GLSMR ranging from 0.74 to 0.94 and 0.76 to 0.96, respectively, at each time point of OLE. None of these analyzes were significant. Sensitivity analyzes adjusted for gender and region also showed similar results to the main analysis.
In a prospective outcome analysis, each doubling of baseline pNfL was associated with an increased hazard of clinical recurrence high MRI activity in all patients during DB (hazard ratio 1.22; 95% CI 1.01-1.48; 95% CI 1.01-1.48; P. = .04). The association between her pNfL level at baseline and all other prospective outcomes did not reach statistical significance, regardless of whether the patient was on teriflunomide or placebo.