Abstract Details

Title Comparison of B-cell Depletion and Natalizumab for Treatment of Multiple Sclerosis: A Semi-supervised Causal Analysis

Topic Multiple Sclerosis

Presentation(s) P8 - Poster Session 8 (8:00 AM-9:00 AM)

Poster/Presentation
Number 1-008

Objective

We compared BCD and NTZ in managing MS patient-reported disability progression using registry-linked electronic healthcare record (EHR) data.

Background

B-cell depleting (BCD) agents (ocrelizumab, ofatumumab, rituximab) and natalizumab (NTZ) are both higher efficacy disease-modifying therapies (DMTs) for multiple sclerosis (MS). However, there is no randomized clinical trial and only limited real-world evidence comparing these drug classes.

Design/Methods The study population included MS patients in the UPMC EHR cohort (2004-2022), including a subset enrolled in a clinic-based MS registry (Pittsburgh, PA), which provided the gold-standard outcome labels. To estimate the comparative treatment effect, we applied a robust and efficient semi-supervised approach to enable analysis of all patients (not just those in the registry) and comprehensively adjusted for confounders that included not only a priori clinical and demographic features but also a high-dimensional set of codified and narrative EHR features selected by knowledge graph. While gold-standard longitudinal disability outcomes were available in registry patients, we imputed the baseline disability status before treatment initiation and the disability progression status after treatment initiation for non-registry patients.

Results In this MS cohort (n=1,738, Age=46±13 years, Non-Hispanic White=86.71%), there was no significant difference between BCD (n=1,245, 71.63%) and NTZ (n=495, 28.37%) in mitigating sustained worsening (ATE=0.012, 95% CI [-0.123, 0.102], p=0.803) or promoting sustained improvement (ATE=-0.0823, 95% CI [-0.194, 0.022], p=0.172) of patient-reported disability. Sensitivity analyses using a 2-year window after treatment initiation confirmed no difference in sustained worsening (ATE=-0.0141, 95% CI [-0.107, 0.080], p=0.895) or sustained improvement (ATE=-0.0713, 95% CI [-0.263, 0.026], p=0.245) between BCD and NTZ. In power analysis, our semi-supervised approach provided greater statistical power than the standard approach of using gold-standard data alone.

Conclusions

This real-world comparative effectiveness analysis based on a novel semi-supervised approach found no difference between BCD and NTZ in managing MS disability progression.

Authors/Disclosures
James D. DiSanto, MSc PRESENTER	Mr. DiSanto has nothing to disclose.
Weijing Tang, PhD	Dr. Tang has nothing to disclose.
Wen Zhu, MD (University of Pittsburgh)	Dr. Zhu has nothing to disclose.
Tianxi Cai	Tianxi Cai has nothing to disclose.
Zongqi Xia, MD, PhD	The institution of Dr. Xia has received research support from National Institute of Health. The institution of Dr. Xia has received research support from Genentech/Roche.

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