Abstract Details

Title Conversion to Non-Active Secondary Progressive Multiple Sclerosis (SPMS) in Patients Who Discontinued or Remained on Natalizumab in the Real-World TYSABRI Observational Program (TOP)

Topic Multiple Sclerosis

Presentation(s) MS and CNS Inflammatory Disease Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 078

Objective To assess conversion to non-active SPMS in patients with relapsing-remitting multiple sclerosis (RRMS) who discontinued or remained on natalizumab in TOP.

Background Long-term natalizumab treatment is associated with a slowing of RRMS disease progression as evidenced by a relatively low probability of reaching major Expanded Disability Status Scale (EDSS) milestones and low rates of 24-week confirmed disability progression over 10 years.

Design/Methods TOP patients enrolled as of March 2020 with baseline and ≥2 additional EDSS measurements were included (N=2958); 1649 patients stayed on natalizumab and 1309 discontinued natalizumab after ≥1 year of treatment. EDSS scores were rebaselined after the last reported relapse to capture relapse-free progression events. Conversion to non-active SPMS was defined as an increase of 1.0 point from an EDSS score ≤5.5 or 0.5 point from an EDSS score ≥6.0 that occurred in the absence of relapse, was confirmed ≥3 months later, and resulted in an overall EDSS score ≥4.0, along with a minimum pyramidal functional system score ≥2. A propensity-score model matched patients who stayed on natalizumab with those who discontinued, controlling for rebaselined covariates (annualized relapse rate and last EDSS score before discontinuation and age and multiple sclerosis duration at discontinuation). The Kaplan-Meier method estimated the conversion to non-active SPMS.

Results After 5 years of follow-up, the cumulative probability (95% confidence interval) of converting to non-active SPMS was lower in patients who stayed on natalizumab (0.14 [0.11–0.17]) than in those who discontinued treatment (0.20 [0.17–0.23]; P<0.0001). Common reasons for natalizumab discontinuation included anti–JC virus antibody positivity (38%) and patient decision (24%). Patients who discontinued most commonly switched to fingolimod (n=410).

Conclusions Rates of conversion to non-active SPMS over 5 years were lower in patients who stayed on natalizumab. These data support the long-term real-world effectiveness of natalizumab in slowing RRMS disease progression.

Authors/Disclosures
Ludwig Kappos, MD, FAAN (RC2NB, University Hospital Basel) PRESENTER	Dr. Kappos has nothing to disclose.
Helmut Butzkueven, MD, MBBS	Dr. Butzkueven has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Oxford Health Policy Forum. The institution of Dr. Butzkueven has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. The institution of Dr. Butzkueven has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck. The institution of Dr. Butzkueven has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. The institution of Dr. Butzkueven has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Butzkueven has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for MSBase . The institution of Dr. Butzkueven has received research support from NHMRC. The institution of Dr. Butzkueven has received research support from Biogen. The institution of Dr. Butzkueven has received research support from Roche. The institution of Dr. Butzkueven has received research support from Novartis.
Maria Trojano (Policlinico - Bari)	Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi_Genzyme. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sandoz. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi-Genzyme. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Janssen.
Heinz Wiendl, MD, FAAN (University of Freiburg)	Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunovant. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Johnson&Johnson / Janssen. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Wiendl has received personal compensation in the range of $0-$499 for serving as a Consultant for Idorsia. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Argenx. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Immunic. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for LTS. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Samsung. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sangamo. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dianthus. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for INmune Bio_Syneos Health. Dr. Wiendl has received personal compensation in the range of $0-$499 for serving as a Consultant for Muna Therapeutics. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Myrobalan Therapeutics. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PSL Group. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Red Nucleus. Dr. Wiendl has received personal compensation in the range of $0-$499 for serving as a Consultant for Swiss Multiple Sclerosis Society. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Teladoc Health. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Toleranzia . Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viatris. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck Serono. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sandoz. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sandoz-Hexal. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cellerys. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Uniqure. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biocryst. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Galapagos. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Idorsia. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biontech. The institution of Dr. Wiendl has received research support from Biogen. The institution of Dr. Wiendl has received research support from Roche. The institution of Dr. Wiendl has received research support from Deutsche Forschungsgemeinschaft. The institution of Dr. Wiendl has received research support from European Union. The institution of Dr. Wiendl has received research support from Argenx. The institution of Dr. Wiendl has received research support from CSL Behring. The institution of Dr. Wiendl has received research support from Merck. The institution of Dr. Wiendl has received research support from UCB. Dr. Wiendl has received research support from Alexion Syneos Health iVH UK Ltd.. The institution of Dr. Wiendl has received research support from Deutsche Myasthenie-Gesellschaft. The institution of Dr. Wiendl has received research support from Winicker Norimed GmbH. The institution of Dr. Wiendl has received research support from Novartis. Dr. Wiendl has received publishing royalties from a publication relating to health care. Dr. Wiendl has received publishing royalties from a publication relating to health care. Dr. Wiendl has received publishing royalties from a publication relating to health care.
Timothy Spelman	No disclosure on file
Shirley Liao	Shirley Liao has received personal compensation for serving as an employee of Biogen.
Stephanie Licata	Stephanie Licata has received personal compensation for serving as an employee of Biogen. Stephanie Licata has received stock or an ownership interest from Biogen.
	No disclosure on file

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