Laura De Giglio1, Francesca De Luca2, Flavia Gurreri2, Ilaria Ferrante2, Luca Prosperini2, Giovanna Borriello2, Esmeralda Quartuccio2, Claudio Gasperini2, Carlo Pozzilli2. 1. From the MS Center Sant'Andrea Hospital (L.D.G., F.G., G.B., C.P.), Department of Human Neuroscience (L.D.G., F.D.L., F.G., I.F., C.P.), and Department of Psychology (F.D.L.), Sapienza University of Rome; Department of Neuroscience San Camillo-Forlanini Hospital (L.P., E.Q., C.G.); and Neurological Center of Latium (G.B.), IRCCS Neuromed, Rome, Italy. laura.degiglio@uniroma1.it. 2. From the MS Center Sant'Andrea Hospital (L.D.G., F.G., G.B., C.P.), Department of Human Neuroscience (L.D.G., F.D.L., F.G., I.F., C.P.), and Department of Psychology (F.D.L.), Sapienza University of Rome; Department of Neuroscience San Camillo-Forlanini Hospital (L.P., E.Q., C.G.); and Neurological Center of Latium (G.B.), IRCCS Neuromed, Rome, Italy.
Abstract
OBJECTIVE: To test a possible benefit of dalfampridine on information processing speed (IPS), a key function for cognitive impairment (CogIm) in multiple sclerosis (MS). METHODS: In this randomized, double-blind, placebo-controlled trial, we included patients with a score on the Symbol Digit Modalities Test (SDMT) under the 10th percentile of the reference value. Patients were randomized in a 2:1 ratio to receive dalfampridine 10 mg or placebo twice daily for 12 weeks. They underwent a comprehensive neuropsychological evaluation at screening (T0), at the end of treatment (T1), and after a 4-week follow-up (T2). The primary endpoint was improvement in SDMT. RESULTS: Out of 208 patients screened, 120 were randomized to receive either dalfampridine (n = 80) or placebo (n = 40). At T1, the dalfampridine group presented an increase of SDMT scores vs placebo group (mean change 9.9 [95% confidence interval (CI) 8.5-11.4] vs 5.2 [95% CI 2.8-7.6], p = 0.0018; d = 0.60 for raw score; and 0.8 [95% CI 0.6-1] vs 0.3 [95% CI 0.0-0.5], p = 0.0013; d = 0.61 for z scores; by linear mixed model with robust standard error). The improvement was not sustained at T2. A beneficial effect of dalfampridine was observed in the Paced Auditory Serial Addition Test and in cognitive fatigue. CONCLUSION:Dalfampridine could be considered as an effective treatment option for IPS impairment in MS. TRIAL REGISTRATION: 2013-002558-64 EU Clinical Trials Register. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with MS with low scores on the SDMT, dalfampridine improves IPS.
RCT Entities:
OBJECTIVE: To test a possible benefit of dalfampridine on information processing speed (IPS), a key function for cognitive impairment (CogIm) in multiple sclerosis (MS). METHODS: In this randomized, double-blind, placebo-controlled trial, we included patients with a score on the Symbol Digit Modalities Test (SDMT) under the 10th percentile of the reference value. Patients were randomized in a 2:1 ratio to receive dalfampridine 10 mg or placebo twice daily for 12 weeks. They underwent a comprehensive neuropsychological evaluation at screening (T0), at the end of treatment (T1), and after a 4-week follow-up (T2). The primary endpoint was improvement in SDMT. RESULTS: Out of 208 patients screened, 120 were randomized to receive either dalfampridine (n = 80) or placebo (n = 40). At T1, the dalfampridine group presented an increase of SDMT scores vs placebo group (mean change 9.9 [95% confidence interval (CI) 8.5-11.4] vs 5.2 [95% CI 2.8-7.6], p = 0.0018; d = 0.60 for raw score; and 0.8 [95% CI 0.6-1] vs 0.3 [95% CI 0.0-0.5], p = 0.0013; d = 0.61 for z scores; by linear mixed model with robust standard error). The improvement was not sustained at T2. A beneficial effect of dalfampridine was observed in the Paced Auditory Serial Addition Test and in cognitive fatigue. CONCLUSION:Dalfampridine could be considered as an effective treatment option for IPS impairment in MS. TRIAL REGISTRATION: 2013-002558-64 EU Clinical Trials Register. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with MS with low scores on the SDMT, dalfampridine improves IPS.
Authors: Iman Adibi; Mehdi Sanayei; Farinaz Tabibian; Neda Ramezani; Ahmad Pourmohammadi; Kiarash Azimzadeh Journal: J Res Med Sci Date: 2022-03-17 Impact factor: 1.852