Moein Amin, Tucker Harvey, Dan Michael Pineda, Ming-Hui Tai, Qiujun Shao, Brandon Brown, show all Accepted 08 Jan 2025, Published online: 21 Jan 2025
ABSTRACT
Aims
To describe the 12-month effectiveness, persistence, tolerability, and safety of ofatumumab (OMB), a highly effective disease-modifying therapy (DMT) for relapsing multiple sclerosis (MS), in a real-world MS population.
Patients & methods
Electronic medical records of patients starting OMB from October 2020 to August 2022 at two comprehensive MS centers were reviewed. Demographics and disease characteristics and 6- and 12-month clinical, patient-reported, and radiologic outcome measures were analyzed.
Results
A total of 175 patients started OMB with mean age 44.9 (SD 10.4) and disease duration 13.6 (SD 9.6) years. The cohort was 74% female, included 81% White and 13% Black American patients, and consisted of 80% relapsing-remitting MS or clinically isolated syndrome. Most (87%) had prior DMT exposure with 38% switching from high efficacy DMT. Over 12 months, 9.7% discontinued OMB (mean 117 days, SD 99.2), with tolerability issues being the most common reason. Thirty-nine (22%) had relapses in the year before starting OMB. By 12 months, only 1 relapse had occurred after approximately 4 months post-treatment initiation.
Discussion
This real-world study demonstrated that OMB is highly effective with robust persistence and good safety and tolerability by 12-month follow-up. Further analyses are planned to examine longer-term outcomes.
1. Introduction
The therapeutic landscape for multiple sclerosis (MS) has expanded rapidly with > 20 disease-modifying therapies (DMTs) available for persons with MS (pwMS) [Citation1]. Monoclonal antibodies (mAb) targeting CD20, a transmembrane antigen expressed on a variety of human B-cell lineage cells, are a class of DMTs with proven efficacy in relapsing MS [Citation2]. Although the full extent of the underlying mechanism of action for this class remains the subject of ongoing research, anti-CD20 mAbs deplete B-cells with CD20 expression through complement dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and induction of apoptosis [Citation3]. Currently, there are three available anti-CD20 mAbs approved for the treatment of MS: ocrelizumab, ublituximab, and ofatumumab (OMB).
OMB is a fully human mAb that can induce B-cell depletion primarily through CDC and to a lesser extent ADCC [Citation4]. In comparison to other anti-CD20 mAbs used in MS, OMB is administered via subcutaneous injection. Its efficacy and safety in relapsing MS were demonstrated in two large randomized, double-blinded, double-dummy controlled trials (RCTs), ASCLEPIOS I and II [Citation5]. In these trials, compared to teriflunomide, subcutaneous OMB in relapsing MS was associated with lower annualized relapse rates (ARR) and confirmed disability progression (CDP) and was well tolerated over the median follow-up duration of 1.6 years. Long-term efficacy and safety of OMB is being evaluated in a single-arm open-label extension study (ALITHIOS), and OMB was shown to be well tolerated without additional safety risks up to 4 years [Citation6,Citation7].
However, real-world effectiveness and safety data for OMB are lacking. Real-world data complement evidence from RCTs and may offer more realistic insights for treatment decision-making at the bedside. In this retrospective study, we aimed to evaluate the effectiveness, persistence, tolerability, and safety of OMB over 12 months in a real-world cohort of pwMS.
2. Patients & methods
2.1. Patient selection
Following institutional review board (IRB) approval (Cleveland Clinic IRB 21–1251), a retrospective review was conducted using the electronic medical record (EMR) of all pwMS prescribed OMB from October 2020 to August 2022 at two large tertiary MS referral centers: Cleveland Clinic Mellen Center and Cleveland Clinic Lou Ruvo Center for Brain Health. In light of the retrospective observational nature of the study, informed consent requirements were waived and approved by the IRB. Patients prescribed OMB who did not start treatment due to lack of insurance coverage or change in preference were excluded. Data were reviewed for up to 12 months or until documentation of OMB discontinuation. The authors used RedCap software to create an encrypted database on secure Cleveland Clinic servers.
2.2. Data collection
2.2.1. Multiple sclerosis performance test
Data were collected from the EMR and Multiple Sclerosis Performance Test (MSPT) assessments. MSPT is a previously validated, self-administered, tablet-based assessment tool for quantifying patient-reported outcomes and neuro-performance measures in pwMS [Citation8] as part of the larger collaboration of MS Partners Advancing Technology and Health Solutions (MS PATHS) [Citation9]. The MSPT provides comparable assessments to the MS Functional Composite (MSFC) [Citation10]. Data are collected at routine follow-up visits and include sections on demographics, disease history, DMTs, PDDS (Patient Determined Disease Steps) [Citation11], neuro-performance outcomes [Citation7] and Neuro-QoL (Quality of Life in Neurological Disorders) [Citation12,Citation13]. Neuro-performance outcomes include four previously validated assessments, such as cognitive assessment through the processing speed test (PST) [Citation14], upper extremity motor function through the manual dexterity test (MDT), lower extremity function through the walking speed test (WST), and vision assessment through the high and low contrast visual acuity test [Citation15]. PST and visual acuity are scored based on the number of correct responses (with a higher score representing better performance), while MDT and WST are measured based on time to completion (with a lower score representing better performance).
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