Author Of 1 Presentation
PS13.02 - Randomized Trial of Amantadine, Modafinil and, Methylphenidate for Multiple Sclerosis Fatigue
Abstract
Background
Methylphenidate, modafinil, and amantadine are commonly prescribed medications for alleviating fatigue in multiple sclerosis (MS); however, the evidence supporting their efficacy is sparse and conflicting.
Objectives
Our goal was to compare the efficacy of these three medications against each other and placebo in patients with MS-related fatigue.
Methods
In this randomized, double-blind, placebo-controlled, four-sequence, four-period crossover trial, patients with MS fatigue received twice-daily oral amantadine, modafinil, methylphenidate, or placebo, each given for up to six weeks. The primary outcome measure was the Modified Fatigue Impact Scale (MFIS) measured while taking the highest tolerated dose. Secondary outcomes included measures of sleepiness, adverse events, and the maximal tolerated dose of each medication.
Results
A total of 141 patients were enrolled and randomly assigned to one of four medication administration sequences. Data from 136 participants were available for the intent-to-treat analysis of the primary outcome. The estimated mean values of MFIS total scores at baseline and the maximal tolerated dose were as follows: 51.3 at baseline, 40.7 with placebo, 41.2 with amantadine, 39.0 with modafinil, and 38.7 with methylphenidate (P=0.20 for the overall medication effect). As compared to placebo (30.6%), higher proportions of participants reported adverse events while taking amantadine (38.6%), modafinil (40.0%), and methylphenidate (39.5%).
Conclusions
Amantadine, modafinil, and methylphenidate were not superior to placebo in improving MS-related fatigue and caused more frequent adverse events. The results of this study do not support an indiscriminate use of amantadine, modafinil, and methylphenidate for the treatment of fatigue in MS. (ClinicalTrials.gov number, NCT03185065.)
Author Of 1 Presentation
P1117 - Clinical and radiologic disease activity in pregnancy and postpartum in multiple sclerosis (ID 1930)
Abstract
Background
Multiple sclerosis (MS) typically begins between the ages of 20 to 40 years and has a female to male ratio of 3:1. As such, MS is primarily diagnosed in women of reproductive age. Several studies have demonstrated that women experience fewer MS relapses during the immunotolerant state of pregnancy; however, an increase in relapses has been observed postpartum. As clinical inflammatory activity postpartum could be confused with other common neurological conditions, magnetic resonance imaging (MRI) detects new inflammatory lesions objectively. No large case series of MRI-defined postpartum inflammatory activity have been published, to our knowledge.
Objectives
To evaluate clinical and radiological inflammatory activity in women with multiple sclerosis during pregnancy and postpartum.
Methods
We performed a retrospective analysis of prospectively collected clinical and MRI reports for women who became pregnant while followed at the UCSF Multiple Sclerosis Center between 2005 and 2018. Annualized relapse rate (ARR) and proportion of brain MRIs with new T2-hyperintense or gadolinium enhancing (Gd+) lesions were compared before, during and after pregnancy.
Results
We identified 155 pregnancies in 119 women (median EDSS 2.0). For the 146 live birth pregnancies, pre-pregnancy ARR was 0.33; ARR decreased during pregnancy, particularly the third trimester (ARR 0.10, p=0.017) and increased in the three months postpartum (ARR 0.61, p=0.012); 16.5% of women experienced a clinically meaningful increase in EDSS. Among 70 pregnancies with paired brain MRIs available, 52.5% had new T2 and/or Gd+ lesions postpartum compared to 32.2% pre-pregnancy (P=0.023). Postpartum clinical relapses were associated with Gd+ lesions (p<0.0001). However, for patients without postpartum relapses, surveillance brain MRIs revealed new T2 and/or Gd+ lesions in 30.9%. Protective effects of exclusive breastfeeding for ≥3 months (odds ratio (OR)=0.20, 95% CI 0.047-0.82) and early initiation of MS therapy (OR=0.28, 0.080-0.98) were observed for relapses.
Conclusions
We confirm prior reports of decreased relapse rate during pregnancy and increased rate in the three months postpartum. We report a significant association between this clinical activity and inflammation on MRI, as well as postpartum radiologic activity even in the absence of relapses. Both clinical and radiologic reassessment may inform optimal treatment decision-making during the high-risk early postpartum period.