Can patient-reported results improve the selection of DMT for multiple sclerosis?
WHILE MOST CLINICAL TRIALS disease-modifying treatments (DMTs) for multiple sclerosis (MS) have focused on reducing relapses, the Phase 3b ARTIOS study (NCT04353492) differs, in an effort to understand differences in outcomes reported by patients (PRO) among approved treatments.1 Designed by Novartis, the ongoing study is evaluating the treatment outcomes of ofatumumab (Kesimpta), its B-cell targeting agent that received FDA approval in 2020, in patients switching from other DMTs to commonly used fumarate bases such as dimethyl fumarate or fingolimod (Gilenya; Novartis).1.2
The open-label, prospective, multicenter, single-arm study plans to enroll 550 patients in 25 countries, with enrollment to be completed in 2023. Patients included in the study are between the ages of 18 and 60, have recurrent 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 up to 3 DMTs and was transitioning from previous therapies due to disease activity (FIGURE1). The study’s principal investigator is Ariele L. Greenfield, MD, director of the 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 subcutaneous treatments of 20 mg 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 are also several exploratory results, including PROs, biomarker assessments, and numerical assessments.
Changes in the Multiple Sclerosis Impact Scale (MSIS-29), Treatment Satisfaction Questionnaire for Medications (TSQM 1.4), Fatigue Scale for Motor and Cognitive Functions (FSMC), and The Hospital Anxiety and Depression Scale (HADS) 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 grip, self-care, health and well-being, leisure, quality of life, role function, social function, and work. The FSMC is a 20-item scale developed to assess cognitive and motor fatigue related to MS, while the HADS assesses anxiety and depression, both common in people with debilitating neurological disorders.
Other non-PRO exploratory endpoints include the change from baseline in the EDSS, the 25-foot timed walk, the 9-hole ankle test, the symbol digit modality test, and the low contrast visual acuity. Additionally, researchers will assess changes in neurofilament lumen 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 uses 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 used in the study provides high-resolution, multi-axis data that can accurately characterize movement and mobility, with data uploaded at each visit. Additionally, in collaboration with Roche, researchers will integrate Floodlight MS, a study-specific advanced digital platform that contains exploratory tests and questionnaires measuring multidimensional functioning in MS patients. Here, exploratory passive surveillance occurs when a phone is carried by the study participant.
The study will exclude people with primary progressive MS or secondary progressive MS with no disease activity, as well as those whose disease has lasted more than 10 years since diagnosis. Pregnant or breastfeeding women, as well as women of childbearing potential, will also be excluded unless they use highly effective forms of contraception during administration and for at least 6 months after discontinuation of the drug at the study. Additionally, the study excludes people 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 compatible with progressive multifocal leukoencephalopathy (PML) or with confirmed PML.