We were so excited to join 8,500+ colleagues from around the world at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis, or ECTRIMS conference, which took place from October 26-28, 2022, in Amsterdam.
One of the reasons this year’s conference was especially compelling for Octave was that our MS Precision Care Solution was featured in 13 posters, including two oral presentations selected by ECTRIMS.
The research we shared continues to validate our Precision Care Solution. Overall the studies showcased the depth and breadth of knowledge around our clinically and analytically validated multivariate biomarker blood test (MS Disease Activity Test) and added to the body of data around our MRI insights program.
Specific highlights from Octave data shared at ECTRIMS 2022 include an oral presentation, presented by Johanna Oechtering, MD, Neurologist at the University Hospital of Basel:
- Serum biomarkers of progression by proteomic search in extreme MS phenotypes (Willemse E., et al.) investigated the associations of ~3000 protein biomarkers in a longitudinal cohort representing extreme phenotypes of MS progression. Octave’s validated custom assay panel, as well as additional multiplex immunoassays performed on the Olink platform, were utilized to enable a deep scan of the proteome. Evidence showing separation of progressors versus non-progressors in multiple novel proteins beyond well-known candidates (NfL and GFAP) demonstrates the potential for developing new multivariate blood-based methods to quantify disease progression.
In addition, Octave presented insights on the company’s multivariate biomarker blood test, the first of its kind and designed specifically for MS, in multiple posters at ECTRIMS 2022. Highlights include:
- Investigation of serum based proteomic biomarker signatures relative to steroid responsiveness and disease activity status in relapsing multiple sclerosis patients (Hoepner R., et al.), which was nominated for one of the five top ranked posters at the conference, aimed at assessing the association of individual proteins, the disease activity score and the four disease pathway scores from the Octave Multiple Sclerosis Disease Activity (MSDA) test in patients from three categories of glucocorticosteroid (GC) responsiveness: stable patients, patients responsive to GC upon relapse and patients resistant to GC upon relapse. Additionally, associations with gadolinium enhancing (Gd+) lesions observed on an associated MRI were analyzed to demonstrate replication of the MSDA test relative to previously reported validation studies. Results showed that the DA score, pathway scores, and several protein biomarkers were significantly associated with both the GC responsiveness categories and the presence of Gd+ lesions. This study underlines the utility of the MSDA test to assess MS patients’ radiographic disease activity status supporting prior validation studies and provides encouraging results that the utility of the MSDA test could be expanded to predict a patient’s responsiveness to steroids.
- Blood serum proteome correlates of multiple sclerosis disease progression as evaluated by clinical and brain atrophy outcomes: a 5-year longitudinal study (Gehman, V., et al.) investigated the correlation of proteomic signatures relative to both clinical and radiographic assessments of disease progression in a cohort of 202 MS patients. Results showed that measurable effects of MS disease progression based on the standardized definition of EDSS change, as well as brain atrophy measurements, can be detected using the proteins included in Octave’s custom assay panel. These results broaden the understanding of progression correlates through the peripheral proteome and will advance the development of a blood-based MS disease progression test..
- Clinical phenotypes from blood serum protein concentration (Gehman, V., et al.), identified six distinct phenotypes of MS patients defined by unsupervised clustering of serum protein concentrations in a study cohort of 220 patients. These pheno-clusters were then evaluated relative to key variables of interest including: disease activity score distributions in clinically stable versus active patients and for comparisons of therapies with diverse mechanisms of action. Identification of distinct clusters of biomarker profiles enables proteomic-based MS subtyping and enhances clinical interpretability of MSDA test results.
- Differential diagnosis of MS patients versus disease state controls and classification of MS subtypes using serum proteomics (Oechtering, J., et al.) outlines Octave’s process to evaluate the performance of proteomic multivariate models to classify patients from different disease states and to classify MS patients based on their subtype. Researchers used Octave’s custom assay panel to measure the concentrations of 20 proteins previously established to be associated with MS. Results demonstrated the assay’s ability to differentially diagnose MS from other disease states with overlapping pathophysiology and to distinguish MS subtypes from one another. These results highlight the potential of Octave’s custom panel to enhance the management of patients in clinical practice beyond assessments of disease activity.
- Longitudinal testing with a multivariate blood serum biomarker panel for multiple sclerosis disease activity: patterns of results in a real-world clinical setting (Hoyt, T., et al.) evaluated 749 patient samples from Rocky Mountain Multiple Sclerosis Clinic using the Octave MSDA test to generate disease activity scores, with the goal of characterizing intra-patient variability upon longitudinal testing. Data showed that 13 stable MS patients in a real-world clinical setting had only minor fluctuations with repeated testing that were on average within the reported analytical variability of the test. These results complement the extensive clinical validation of the MSDA test with real-world examples of repeated testing and support the use of the MSDA test as a clinical adjunct for longitudinal monitoring of patients to help inform the degree of biologic disease stability.
- Matched plasma modification for calculating a disease activity score in a serum-validated multivariate proteomic multiple sclerosis disease activity test (Hu, W., et al.) sought to validate the MSDA test in plasma by establishing a process to adjust protein concentrations prior to calculating disease activity and pathway scores. Researchers analyzed matched serum and plasma samples and found that a linear regression-based model could be utilized to adjust plasma protein concentrations and determine equivalent scores. These findings support the use of the MSDA test in retrospective studies for which only plasma samples are available.
- Multivariate proteomic analysis and the relationship with axonal pathology in multiple sclerosis: a longitudinal 5-year diffusion tensor imaging study (Jakimovski, D., et al.) presented by Octave’s collaborators at the University at Buffalo sought to determine the predictivity of proteins analyzed using the Octave MSDA test with current and future microstructural axonal brain pathology in a heterogeneous group of people with MS. Researchers determined that serum glial fibrillary acidic protein (GFAP) levels are predictive of future disability progression and that multiple proteomic biomarkers are independently associated with greater axonal brain pathology, with superior predictive ability when compared to single serum-based measures.
- Complement activation predicts disease severity in multiple sclerosis (Oechtering J., et al.) presented by collaborators at University Hospital Basel discussed how complement factor (CF) activation in combination with immunoglobulins (Ig) might play an important pathophysiological role in MS. Researchers investigated if intrathecal CF activation is increased in MS patients with intrathecal IgM synthesis, and evaluated associations with expanded disability status score (EDSS), MS severity score (MSSS), and neurofilament light chain (NfL) levels in the cerebrospinal fluid. They found that brain-compartmentalized early CF activation cascade is increased in MS and correlates with EDSS as well as future MSSS and NfL levels, pointing toward an important pathophysiological role for CF and their potential as novel therapeutic targets.
Data shared at ECTRIMS 2022 by the company around its MRI-specific protocol that combines human expertise with innovative imaging technology to deliver a highly-valued and personalized, MS-specific report to track a patient’s disease over time, includes:
- Study Design: The impact of quantitative structured MRI reports on clinical decision making in MS (Leyden, K., et al.) shares the design of an ongoing study to understand the impact of structured quantitative MRI brain reports of patients with MS on MS specialist neurologists’ understanding, reporting, satisfaction and clinical decision making relative to the standard of care reports available. Researchers believe that understanding the effect of standard of care versus quantitative structured MRI reports on clinical decision making is crucial to translating quantitative imaging metrics from research used to routine clinical practice.
- Multiple sclerosis MRI reports vary among neuroradiologists (Keshavan, A., et al.) outlines how inter-rater variability of MRI reports among neuroradiologists’ phrasing and lesion detection can lead to discrepant reports. Researchers sought to quantify the level of agreement between three neuroradiologists’ assessments of MS-specific reporting of brain MRIs, with results showing substantial to near-perfect agreement in the detection of enhancing lesions but only slight-to-fair agreement in all other categories, including the detection of new and enlarging lesions. This varying agreement highlights the need to incorporate quantitative methods, including the MRI component of Octave’s Precision Care Solution, to reduce reporting variability and improve the detection of subtle, clinically significant features that impact patient care.
- Tracking longitudinal change in brain volumes through conditional quantiles (Keshavan, A., et al.) developed and implemented cutting-edge statistical models to help physicians understand whether changes in brain volume over time are of concern in individual patients. By incorporating heterogeneous and longitudinally acquired MRI image quality measurements, Octave established personalized and informative brain growth charts. These brain charts promise to revolutionize physician decision support systems for the management of MS patients by providing more informative and clearer representations of whether a change in volume is clinically significant at an individual patient level.
- Brain charts for people living with multiple sclerosis (Keshavan, A., et al.), established the brain-science equivalent to adolescent growth charts for ventricle volume in patients living with MS. As the ventricles change naturally with age and may be susceptible to biases associated with acquisition hardware, imaging protocol, and image quality, it can be difficult to interpret normative percentiles of these volumes at a patient level. Advanced statistical modeling based on WHO-recommended practices was employed to account for variations in volume change that may be driven by differences in image quality. While these are initial explorations, growing databases of heterogeneously acquired MRIs in patients with MS will facilitate increasingly precise assessments of brain structure for clinical practice settings.
These presentations by Octave at ECTRIMS 2022 underscore the company’s dedication to the pursuit of clinical insight and to addressing the various unmet needs associated with MS as it builds the model for the future of management for neurodegenerative diseases. Octave recently announced the commercial launch of its solution, which is now available and in use at MS centers around the United States.
