Predicting Disease Activity and Rebound Risk in MS Patients Treated With Sphingosine-1-phosphate Receptor Modulators (S1PRM)
- Conditions
- Multiple Sclerosis
- Interventions
- Other: S1PR analysis on immune cells
- Registration Number
- NCT05828901
- Lead Sponsor
- Insel Gruppe AG, University Hospital Bern
- Brief Summary
Sphingosine 1-Phosphate (S1P) receptor modulators (S1PRMs) are part of the evolving treatment landscape of Multiple Sclerosis (MS) immunotherapies. They target the G-protein coupled S1P receptor, among other localizations expressed at the surface of lymphocytes. Binding as a functional antagonist leads to internalization of the receptor and therefore lymphocyte sequestration in the secondary lymphoid organs. The first S1PRM approved was fingolimod. More recently newer generation S1PRMs like ozanimod have been approved, which possess differences in receptor affinities, pharmacokinetics and indications (including Secondary Progressive MS or Ulcerative Colitis). Several retrospective analyses have shown that, upon cessation of fingolimod, pronounced relapse of the MS-disease called "rebound disease activity" may occur. Indeed, these relapses, sometimes with considerable severity, take place in up to 10% of patients. The risk of rebound disease of the newer generation S1PRM are not well defined.
Although of utmost importance, predictive biomarkers of treatment efficacy in general and in special circumstances, e.g. an impending rebound when S1PRM cessation is planned, are scarce.
In this prospective, exploratory observational study, we aim to investigate the predictive potential of the lymphocytic S1PR1 and 5 expression prior to treatment initiation with the newer generation S1PRM ozanimod on the future disease activity ("on treatment" part). Additionally, in a post-treatment part ("off treatment"), the incidence of rebound disease and the predictive potential of the lymphocytic S1PR1 and 5 expression will be examined in patients, where ozanimod has to be stopped due to clinical reasons.
T and B cells from patient blood samples obtained prior to treatment start/cessation and 3 - 6 months after start/cessation will be isolated and S1PR1 and 5 staining intensity will be assessed by flow cytometry (FACS). Clinical assessments (relapse assessment, EDSS, medical history etc.) will be performed at every visit and MRI evaluation, following our standard clinical and MRI MS protocol. MRI disease activity will serve as the primary endpoint for both study groups. The relationship between the flow cytometric staining intensity and the defined endpoints will be assessed statistically by using comparative statistical approaches and multivariable regression analysis where needed for both time points. The data collected will correlate the expression pattern of S1P receptors by T and B lymphocytes to the proxy of paraclinical activity as predictive biomarkers for disease activity on treatment and after treatment discontinuation.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Relapsing Remitting Multiple Sclerosis starting Ozanimod S1PR analysis on immune cells - Relapsing Remitting Multiple Sclerosis stopping Ozanimod S1PR analysis on immune cells -
- Primary Outcome Measures
Name Time Method "Off treatment" MRI disease activity Between 3 - 6 months after start of any new MS drug in our center Enhancing T1 lesions or new/enlarging T2 lesions - in the re-baseline MRI of the subsequent immunotherapy after cessation of ozanimod, performed during routine clinical care
"On treatment" MRI disease activity Between 3 - 6 months after start of any new MS immunotherapy in our center compared to the previous scan Enhancing T1 lesions or new/enlarging T2 lesions - in the re-baseline MRI (change from baseline), defined as first MRI after treatment start performed during routine clinical care
- Secondary Outcome Measures
Name Time Method "Off treatment" Relapse rate and severity In the first 6 months after ozanimod cessation Relapse rate (six-monthly relapse rate)
"On treatment" Disability progression In the first year of ozanimod treatment Disability progression (measured as Expanded Disability Status Scale (EDSS), 9-Hole Peg Test (9-HPT), timed 25-Foot Walk Test (T25ftWT) and Symbol Digit Modalities Test (SDMT). Additional questionnaires (Fatigue Scale for Motor and Cognition (FSMC) to assess MS-related fatigue, Hospital Anxiety and Depression Scale (HADS) to assess anxiety and depression, Epworth Sleepiness Scale (ESS) to assess sleepiness and Multiple Sclerosis Impact scale (MSIS-29) to assess health-related quality of life) will be carried out.
"Off treatment" Severity In the first 6 months after ozanimod cessation Severity (measured as EDSS increase during relapse) and EDSS progression in the first 6 months after ozanimod cessation will be investigated. The following exploratory endpoints will also be assessed: 9-HPT, T25ftWt, SDMT, FSMC, HADS, ESS, MSIS-29.
"On treatment" Relapse rate In the first year of ozanimod treatment Relapse rate
Trial Locations
- Locations (1)
Neurology department
🇨ðŸ‡Bern, Switzerland