Regulatory Activities preferred terms (PT) was searched to identify Individual Safety Reports (ISR) where ISO was documented as the primary suspect for the sleep-related AE. Reporting odds ratios (ROR) with 95% CI were calculated to indicate the strength of the signal for the sleep-related AE from ISO use. Results: There were 168,341 ISR which specified ISO as the primary suspect in the AE. The overall risk of sleep-related AE with ISO was examined in 2 analyses: (i) ISO Introduction: Fatigue is one of the most debilitating symptoms of multiple sclerosis (MS), and is present in up to 80% of persons with MS (pwMS). It has also more recently been realized that sleep disorders, including insomnia, are highly prevalent in pwMS. Insomnia is often associated with daytime impairments, such as fatigue, however, few studies have examined the extent to which insomnia is related to fatigue in this population. Thus, this study aimed to examine the relationship between insomnia symptom severity and fatigue in pwMS. Methods: Preliminary analyses were conducted to examine 13 participants with relapsing-remitting MS (RRMS) who completed a demographic questionnaire, the Insomnia Severity Inventory (ISI), the Fatigue Severity Scale (FSS), and the Beck Depression Inventory Fast Screen (BDI-FS). Participants were excluded if they had experienced an exacerbation of symptoms or change in medical regimen within 30 days of participation. A multiple regression analysis, with ISI and BDI-FS as predictor variables and FSS as outcome variable, was utilized to assess the relationships between insomnia symptom severity, depression, and fatigue. Results: Participants (M age = 45.6, SD = 6.4) were primarily women (n = 9). ISI scores ranged from 2 -26, with 30.7% endorsing no significant insomnia, 38% endorsing subthreshold insomnia, and 30.7% endorsing clinically significant insomnia (moderate and severe). ISI scores were significantly associated with FSS scores, after adjusting for BDI-FS scores, b=1.50, SE b =.40, 95% CI b [.61, 2.40], p < .01. The overall model explained 62% of the variance seen in FSS scores (R 2 = .62). Conclusion: Insomnia symptom severity is related to severity of fatigue in those with RRMS. Thus, the treatment of insomnia may lead to significant improvements in fatigue in pwMS. Support (If Any):