Abstract Details

Title Impact of Switching from Natalizumab to a Moderate versus High Efficacy DMT in Clinical Practice at 24-Month Follow-Up

Topic Multiple Sclerosis

Presentation(s) S29 - Multiple Sclerosis: Disease-modifying Therapy (2:24 PM-2:36 PM)

Poster/Presentation
Number 008

Objective To assess the impact of switching from natalizumab (NTZ) to a moderate (Mod) disease modifying therapy (DMT) vs. high efficacy therapy (HET) in multiple sclerosis (MS) patients at 24-month follow-up.

Background Long-term use of NTZ is limited by potential safety risks that can be reduced by switching to an alternative therapy. However, NTZ discontinuation may trigger rebound disease, resulting in disability. Our previous study showed patients switching to Mod DMT vs. HET were at higher risk of early MRI disease activity by 6 months.

Design/Methods Patients discontinuing NTZ at two MS centers (n=556) who switched to Mod DMT (n=270) vs. HET (n=130) were assessed using propensity score (PS) weighting. Outcomes included ARR ratio and proportions with new T2 and/or gadolinium enhancing (GdE) lesions, absence of disease activity (a composite measure of no relapses and/or MRI activity), and 20% worsening of the timed twenty-five foot walk (T25FW) and 9-hole peg test (9-HPT). All outcomes were reported as Mod DMT vs. HET.

Results In our cohort, 48.6% switched to Mod DMT (dimethyl fumarate, n=130; fingolimod, n=140) vs. 23.4% who switched to HET (ocrelizumab, n=106; rituximab, n=17; alemtuzumab, n=7). Reasons for NTZ discontinuation included PML risk (54.9%), breakthrough disease (15.3%), and adverse effects (17.3%). At 24-month follow-up, there were no differences in ARR [OR=1.44, 95% CI (0.69-1.59), p=0.334)]. However, patients switching to Mod DMT had higher proportions with new T2 lesions [OR=2.15, 95% CI (1.18-3.01), p=0.011], new GdE lesions [OR=1.99, 95% CI (1.12-2.73), p=0.022], and 20% worsening of the T25FW [OR=1.83, 95% CI (1.06-3.02), p=0.043] and 9-HPT [OR=1.81, 95% CI (1.05-3.56), p=0.044]; and lower proportion with absence of disease activity [OR=0.41, 95% CI (0.21-0.71), p=0.004].

Conclusions At 24 months, NTZ switchers to Mod DMT had lower cumulative probability of no disease activity by 24 months and were at higher risk of disability accumulation.

Authors/Disclosures
Carrie M. Hersh, DO, MSc, FAAN (Cleveland Clinic Lou Ruvo Center for Brain Health) PRESENTER	Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech_GN41791. Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme. Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol-Myers Squibb . Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon Therapeutics. Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genzyme. Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Hersh has received research support from Biogen. The institution of Dr. Hersh has received research support from Novartis. The institution of Dr. Hersh has received research support from Genentech_GN41791. The institution of Dr. Hersh has received research support from PCORI. The institution of Dr. Hersh has received research support from Bristol Myers Squibb.
Haleigh C. Harris	No disclosure on file
Devon Conway, MD	Dr. Conway has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis Pharmaceuticals. Dr. Conway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for AstraZeneca. Dr. Conway has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Conway has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Conway has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Conway has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. Conway has received research support from Novartis. The institution of Dr. Conway has received research support from BMS. The institution of Dr. Conway has received research support from Biogen.
Le Hua, MD, FAAN (Cleveland Clinic)	Dr. Hua has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Hua has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Hua has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon. Dr. Hua has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Hua has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genzyme. Dr. Hua has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Hua has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hua has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Hua has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for TG Therapuetics. The institution of Dr. Hua has received research support from Genentech.

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