By leveraging digital technologies, the single-arm ARTIOS study will provide unique and comprehensive data that may enrich treatment outcomes for patients with relapsing multiple sclerosis.
ALTHOUGH MOST CLINICAL TRIALS of multiple sclerosis (MS) disease-modifying therapies (DMTs) have focused on reducing relapses, the phase 3b ARTIOS study (NCT04353492) differs, with a goal of understanding differences in patient-reported outcomes (PROs) among approved therapies.1 Designed by Novartis, the ongoing study assesses treatment outcomes of ofatumumab (Kesimpta), its B cell–targeting agent that received FDA approval in 2020, in patients who switch from other commonly used fumarate-based DMTs such as dimethyl fumarate or fingolimod (Gilenya; Novartis).1,2
The single-arm, prospective, multicenter, open-label study plans to enroll 550 patients across 25 countries, with enrollment expected to be completed in 2023. Patients included in the study are aged 18 to 60 years, have relapsing forms of MS—including relapsing MS and secondary progressive MS—and have Expanded Disability Status Scale (EDSS) scores between 0 and 4. Each patient has a treatment history with a maximum of 3 DMTs and was transitioning from previous therapies because of breakthrough disease activity (FIGURE1). The principal investigator of the study is Ariele L. Greenfield, MD, director of Palo Alto Medical Foundation Multiple Sclerosis Center.
In the study, patients will receive 3 loading doses of ofatumumab over the first 14 days, followed by 20-mg subcutaneous treatments every 4 weeks. Over a 96-week treatment period, patients will be assessed on annualized relapse rate and safety, using adverse events, laboratory abnormalities, and treatment discontinuations. There also are several exploratory outcomes, including PROs, biomarker evaluations, and digital evaluations.
Changes in the Multiple Sclerosis Impact Scale (MSIS-29), Treatment Satisfaction Questionnaire for Medication (TSQM 1.4), Fatigue Scale for Motor and Cognitive Functions (FSMC), and Hospital Anxiety and Depression Scale (HADS) scores will be among the PROs observed. MSIS-29, a common PRO, measures coordination, fatigue, flexibility, muscle performance, muscle tone and spasticity, balance and falls, reach and grasp, self-care, health and wellness, leisure, quality of life, role function, social function, and work. The FSMC is a 20-item scale developed to assess MS-related cognitive and motor fatigue, whereas the HADS is assesses anxiety and depression, both common in those with debilitating neurological disorders.
Other exploratory non-PRO end points include change from baseline in EDSS, Timed 25-Foot Walk, 9-Hole Peg Test, Symbol Digit Modalities Test, and low-contrast visual acuity. Additionally, investigators will evaluate change in neurofilament light and glial fibrillary acidic protein, 2 markers of neuroinflammation and degeneration, and the proportion of patients with no evidence of disease activity status 3.
The innovative study design also employs digital tools such as actigraphy and an electronic clinical outcome assessment handheld as an electronic diary to collect data on daily activity, sleep quality, and injection reactions. The ActiGraph monitor being used in the study provides high-resolution multiaxis data that can accurately characterize movement and mobility, with data downloaded at each visit. Additionally, in collaboration with Roche, investigators will incorporate Floodlight MS, an advanced study-specific, digital platform that contains exploratory tests and questionnaires measuring multidimensional functioning in patients with MS. Here, exploratory passive monitoring occurs when a phone is carried by the study participant.
The study will exclude those with primary progressive MS or secondary progressive MS without disease activity, as well as those with a disease duration of more than 10 years since diagnosis. Pregnant or lactating women, as well as women of childbearing potential, will be excluded as well, unless they are using highly effective forms of contraception during dosing and for at least 6 months after stopping study medication. Additionally, the study excludes those with an active chronic disease of the immune system other than MS; those with active systemic bacterial, fungal, or viral infections; and those with neurological symptoms consistent with progressive multifocal leukoencephalopathy (PML) or with confirmed PML.