Why are we conducting this research project?

Multiple sclerosis (MS) is a chronic, progressive and disabling disease of the central nervous system where the immune system attacks the myelin sheet of the axons. MS is also the most common non-traumatic cause of disability in young adults.
Newer MS drugs, so-called disease modifying therapies, can reduce inflammatory activity by weakening the immune system. However, weakening the immune system can also cause side effects such as an increase risk for infectious diseases. Therefore, it is important to determine the optimal dose and timing of medication for each individual, i.e., to treat as little as possible but also as much as necessary.
The individual situation of patients’ needs to be carefully considered and more personalized treatment and care strategies in MS are urgently needed.

Where is the research conducted?

Multiple sclerosis (MS) is a chronic, progressive and disabling disease of the central nervous system where the immune system attacks the myelin sheet of the axons. MS is also the most common non-traumatic cause of disability in young adults.
Newer MS drugs, so-called disease modifying therapies, can reduce inflammatory activity by weakening the immune system. However, weakening the immune system can also cause side effects such as an increase risk for infectious diseases. Therefore, it is important to determine the optimal dose and timing of medication for each individual, i.e., to treat as little as possible but also as much as necessary.
The individual situation of patients’ needs to be carefully considered and more personalized treatment and care strategies in MS are urgently needed.

> Why are we conducting this research project?

Multiple sclerosis (MS) is a chronic, progressive and disabling disease of the central nervous system where the immune system attacks the myelin sheet of the axons. MS is also the most common non-traumatic cause of disability in young adults.
Newer MS drugs, so-called disease modifying therapies, can reduce inflammatory activity by weakening the immune system. However, weakening the immune system can also cause side effects such as an increase risk for infectious diseases. Therefore, it is important to determine the optimal dose and timing of medication for each individual, i.e., to treat as little as possible but also as much as necessary.
The individual situation of patients’ needs to be carefully considered and more personalized treatment and care strategies in MS are urgently needed.

With MultiSCRIPT we want to find such better strategies. MultiSCRIPT evaluates which new personalized care strategies ensure no evidence of disease activity, while achieving better patient outcomes, fewer adverse events and improved care. MultiSCRIPT uses the procedures and high-quality real-world data collection of the SMSC usual care to avoid almost all the burden for participants that traditional clinical trials would require. This innovative approach will make clinical research part of usual care in MS.

> Where is the research conducted?

MultiSCRIPT is conducted as part of usual care of patients with MS. It is fully embedded within the SMSC that was established in 2012 and now has 8 centers across Switzerland. As of September 2022, the SMSC included >1600 of the estimated 15,000 patients living with MS in Switzerland. Patients participating to the SMSC come every 6 to 12 months for outpatient routine visits with a standardized neurological examination and evaluations of relapses and disability status, blood sampling and magnetic resonance imaging (MRI) to detect disease activity in the brain or spinal cord.

> What is a MultiSCRIPT Cycle?

MultiSCRIPT aims to be a continuous learning system. Each comparison of a new personalized strategy in a pragmatic trial is one learning cycle, which ends with a decision whether the strategy is better and should be implemented in usual care, or not. Because each pragmatic trial ends with the begin of a new pragmatic trial, it is a continuous cycle of knowledge generation. We now start with the first pragmatic trial. It is designed to lay the foundation for subsequent cycles, in which a new strategy, based on the learnings of this first cycle, will be evaluated. The continuous evaluation in MultiSCRIPT initiates an evolutionary process that systematically develops, improves and personalizes treatment and care of patients living with MS in Switzerland and beyond.

> What is the purpose of MultiSCRIPT Cycle 1?

TO BE ADDED LATER

There is a novel blood marker that indicates disease activity and may predict worsening of the disease, the neurofilament L (NfL). NfL is a protein from neurons and released in the cerebrospinal fluid when the neurons are damaged. Higher levels of sNfL are associated with disease activity and higher risk of relapses; conversely, patients under effective treatment have lower levels of sNfL. sNfL offers a novel way to monitor and even predict disease activity, and to personalize MS therapy. We believe that intensive sNfL monitoring in addition to usual care could not only improve patients’ quality of life by reducing their treatment burden (e.g., by reducing the drug dose) and risk for side effects (e.g., infections) but also may  result in fewer patients with disease activity by early and more sensitive biomarker-guided treatment escalation.

In this first cycle of MultiSCRIPT we will investigate a 6-monthly biomarker monitoring strategy including sNfL compared with the current usual care.

> Who can participate to MultiSCRIPT Cycle 1?

All patients with RRMS in the SMSC for at least a year will be eligible. We expect to include at least 915 patients.

> What does it mean for me if I would like to participate to MultiSCRIPT Cycle 1?[LH1] 

TO BE ADDED LATER

If you wish to participate and you are already in the SMSC, further information will be given to you by your SMSC study nurse and physician during your next planned visit. If you accept to take part to the first cycle of MultiSCRIPT, you will be treated in one of two ways. Either have intensive sNfL monitoring where we need one blood sample every 6 months or you will have the normal treatment without this blood analysis which you would receive also if you were not taking part in this cycle, plus the established clinical and MRI evaluation used in the SMSC. The selection of the treatment strategy is made randomly to make sure it is a fair comparison.

If you are allocated to the usual care group, you will continue with your usual visits schedule that can be 6-monthly or 12-monthly as decided with your SMSC physician. If you are allocated to the usual care group, you will continue your usual care within SMSC with 6-monthly or annual visits depending on your current already established usual care. If you are allocated to the intervention group you will have 6-monthly visits during which sNfL will be assessed. sNfL information will then be used by your physician in addition to the usual care assessments to suggest a more personalized approach to your treatment which may include 1) escalation (i.e., increase dose or strength of DMT) in case of disease activity and/or high sNfL or 2) de-escalation (i.e., decrease dose or strength of DMT with potentially less side effects) in case of constant absence of disease activity and low sNfL.

Regardless to which group you have been allocate, anytime you come to a visit within the SMSC (6-monthly or 12-monthly) you will receive usual care as normal including EDSS assessment and documentation of occurrence of relapses. You will be invited to perform an MRI at least once year as per usual care in the SMSC. Six-monthly MRI might be recommended at your physician discretion. Of course, at all time you may trigger a visit with your physician according to your needs and changes in your treatment may occur regardless of sNfL values or if you are in the usal care or intervention group.

You will also be asked to complete a quality of life questionnaire three time during the course of the trial: before randomization, after 1 year and after 2 years. Apart from this additional questionnaire, we will not collect any additional data beyond what is already collect through SMSC.

> What are the possible benefits of the study

We will consider intensive biomarker monitoring strategy better than usual care if either more patients have no evidence of disease activity, or more patients have a better health-related quality of life.

Intensive and precise monitoring of treatment response could help to avoid over- or under-treatment and thus minimize side effects and dangers as well as the corresponding costs while achieving optimal efficacy. In addition, the number of magnetic resonance imaging (MRI) scans currently used to detect disease activity and the associated costs could be reduced in the future. This would also be a further gain in quality of life for some people with MS, as some have difficulty lying still for 30 minutes due to disease-related tension and pain, making the imaging examination challenging for both the patient and the interpretation of the results. Finally, low-effort monitoring of NfL levels can provide additional reassurance to individuals, which can positively impact quality of life in an unpredictable disease such as MS.

> What are the possible risks of the study?

We do not anticipate any risk for the study apart from the side effects inherent to the DMTs you already receive.

Do we want to mention that we cannot exclude the risk of exacerbation of relapses due to de-escalation?

Do we want to add “What information do you hold about me and how do you keep it private?”

> How may I participate?

To participate in the MultiSCRIPT cycle 1 trial or in other future cycles, please reach to one of the SMSC centers nearest to you

Would be great to have a list of contact for each centers

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