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The people with SPMS treated with natalizumab in the phase 3 ASCEND in SPMS trial (NCT01416181) had a decrease in their Multiple Sclerosis Impact Scale mean psychological scores from 39.1 at baseline to 36.7 at week 96, 21 which, although it was nonsignificant, was disconnected from longitudinal PROM changes with a steady decline in EDSS scores and the T25-FW

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These findings suggest that adverse events associated with tapering may be relatively common and support HHS recommendations for more gradual dose reductions when feasible and careful monitoring for withdrawal, substance use, and psychological distress.9 "Previous research has examined adverse outcomes associated with discontinuing long-term opioids.10-14 This analysis demonstrated associations between adverse outcomes and a more sensitive indicator of opioid dose reduction (15% from baseline)