Abstract Details

Title Predicting Natalizumab Discontinuation due to Breakthrough Disease in Multiple Sclerosis Patients

Topic Multiple Sclerosis

Presentation(s) P4 - Poster Session 4 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-035

Objective

Determine patient characteristics that predict breakthrough disease on natalizumab.

Background

Natalizumab is a highly effective disease modifying therapy (DMT) for multiple sclerosis (MS). However, some patients experience breakthrough disease despite natalizumab treatment. Characteristics that predict natalizumab discontinuation due to breakthrough disease would facilitate treatment planning.

Design/Methods We reviewed charts of MS patients discontinuing natalizumab treatment. Demographic data (age and disease duration at natalizumab start, gender, race), disease characteristics (prior DMTs, presence of new/enlarging T2 lesions or gadolinium enhancing lesions on magnetic resonance imaging, relapses in the year prior to starting natalizumab), performance test results (assistive device usage, timed 25 foot walk, and nine-hole peg test), other patient characteristics (tobacco use, vascular comorbidities) and patient reported outcomes including performance scales and the patient health questionnaire 9 (PHQ9) were collected. The reason for natalizumab discontinuation was recorded (breakthrough disease, intolerance, progressive multifocal leukoencephalopathy risk, or other). Patients discontinuing due to inflammatory disease or disability progression were classified as having breakthrough disease. Missing data was handled with imputation. Logistic regression was used to determine odds ratios (OR) between patient characteristics and breakthrough disease occurrence.

Results

There were 556 natalizumab discontinuers, of whom 85 (15.2%) stopped because of breakthrough disease. The average age at natalizumab initiation was 41.2 years and the sample was 68% female. There were 527 patients (94.8%) with relapsing-remitting MS and 26 (4.7%) with progressive relapsing multiple sclerosis (PRMS). Significant predictors of discontinuation due to breakthrough disease included: number of prior DMTs (OR=1.17, p=0.045), PRMS phenotype (OR=99.6, p=0.01), unilateral assistive device (OR=3.9, p=0.0001), bilateral assistive device (OR=1.96, p=0.046), wheelchair (OR=2.49, p=0.03), and PHQ9 score (OR=1.03, p=0.01). An interaction between PRMS and age approached significance (OR=0.92, p=0.06).

Conclusions

In our cohort, natalizumab discontinuation due to breakthrough disease was very likely in PRMS patients, though this risk decreased with age. Walking disability also strongly predicted breakthrough disease.

Authors/Disclosures
Devon Conway, MD PRESENTER	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 Alexion. Dr. Conway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Conway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amgen. Dr. Conway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. 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.
Haleigh C. Harris	No disclosure on file
Carrie M. Hersh, DO, MSc, FAAN (Cleveland Clinic Lou Ruvo Center for Brain Health)	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.
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 $10,000-$49,999 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 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 as a Consultant for Novartis. Dr. Hua has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octave Bioscience. 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 Speakers Bureau for TG Therapuetics. The institution of Dr. Hua has received research support from Genentech.

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