Background

Whilst the introduction of disease modifying treatments (DMTs) has transformed the management of people with early/relapsing MS (pwRMS), the use of DMTs in people with MS who are largely or completely wheel chair-dependent (EDSS>6.5) remains controversial. Evidence suggests that slowing or stopping disease deterioration is possible even past this arbitrary (loss of ambulatory function) threshold. Pathology and anecdotal clinical data support the hypothesis that even at an advanced stage of MS (AMS) inflammatory activity is a key driver of functional decline and that effective immunotherapy may halt this process. Cladribine tablets are a highly effective and central nervous system (CNS) penetrant DMT for people with highly-active RMS. It effectively depletes B cells, particularly memory B cells, a likely key mechanism of disease control in MS. Evidence, suggesting that (i) a significantly higher number of CNS axons supply upper compared to lower limb functions and (ii) longer axons are more vulnerable to the effects of focal inflammatory demyelination than shorter ones, corroborate our hypothesis that upper limb function can be protected even beyond EDSS=6.5.

Objectives

Primary Objective: To investigate whether cladribine tablets over 24 months is an effective DMT in people with AMS (pwAMS; EDSS=6.5-8.5) as measured using the 9-hole peg test (9HPT) peg speed.

Secondary Objectives: To establish whether there is a difference in pwAMS between treatment with cladribine tablets or placebo in (i) blood/serum biomarkers of inflammation (lymphocyte subsets) and/or neurodegeneration (neurofilament light chain), (ii) MRI loss of brain volume and spinal cord cross sectional area, (iii) T₂ lesion burden, (iv) hypo-intense lesions on T₁ weighted scans, (v) quality of life, and (vi) whether cladribine is a cost-effective treatment for pwAMS.

Methods

Randomised, double-blind, placebo-controlled phase IIb trial. To detect a 15% treatment effect in 9HPT peg speed with 90% power at 5% significance and 20% drop-out over 104 weeks n=200 pwAMS will be recruited across 20 UK MS centres.

Results

Protocol and ancillary documents have been submitted for ethics approval. So far 17 centres have agreed to recruit pwAMS for ChariotMS. Due to the COVID-19 pandemic start of recruitment has been deferred to 04 Jan 2021.

Conclusions

ChariotMS will be the first DMT-trial focussing on pwAMS. If successful, ChariotMS would expand the DMT landscape to include pwAMS and provide a platform for add-on therapies.

Background

A strategy for timely multiple sclerosis (MS) care was described in the policy report, Brain health: time matters in multiple sclerosis. Building on this report, multiple stakeholder groups participated in a modified Delphi process to define acceptable, good and high-quality brain health-focused MS care. These benchmarks were incorporated into an Excel-based quality improvement (QI) tool. The first prototype of this tool was piloted in three MS centers; local analysis of results led to improvements in clinical practice in those centers.

Objectives

We aimed to improve the clinical usability of the QI tool and to test the applicability of a refined version in different healthcare settings.

Methods

The recommendations from all three centers that participated in the initial pilot study were gathered and used to prepare a refined prototype of the QI tool (prototype II). MS centers worldwide have been invited to conduct a service evaluation using prototype II as part of a larger pilot study of 10–20 MS centers across a broad geographical area. Each participating site will review the medical records of 36 adults with MS (at representative stages of the care pathway) and input the data requested into the tool. To assess whether the QI tool can be applied in MS centers globally, study sites will be asked to complete a survey following their service evaluation. The survey asks about ease of use of the tool, its usefulness for facilitating local change, relevance of the data captured and key data for repeated use.

Results

Prototype II has separate spreadsheets for entering information on patients at different stages of the care pathway; fields are tailored to the different patient populations so there is less data to input per patient. Data validation programming prevents the insertion of invalid information. To assist MS centers in analyzing their findings, improved visual summaries of clinic-level and patient-level results are generated within the tool; these auto-populate when the required fields in the data input spreadsheets are completed. Prototype II will also support future language translations. More than 18 MS centers have so far expressed interest in trialing prototype II of the QI tool; preliminary insights from selected study sites will be presented.

Conclusions

Following further refinements, widespread roll-out of the QI tool will enable MS centers to collect data to benchmark their clinical standards and to support service improvement.

Background

A strategy for timely multiple sclerosis (MS) care was described in the policy report, Brain health: time matters in multiple sclerosis. Building on this report, multiple stakeholder groups participated in a modified Delphi process to define acceptable, good and high-quality brain health-focused MS care. These benchmarks were incorporated into an Excel-based quality improvement (QI) tool. The first prototype of this tool was piloted in three MS centers; local analysis of results led to improvements in clinical practice in those centers.

Objectives

We aimed to improve the clinical usability of the QI tool and to test the applicability of a refined version in different healthcare settings.

Methods

The recommendations from all three centers that participated in the initial pilot study were gathered and used to prepare a refined prototype of the QI tool (prototype II). MS centers worldwide have been invited to conduct a service evaluation using prototype II as part of a larger pilot study of 10–20 MS centers across a broad geographical area. Each participating site will review the medical records of 36 adults with MS (at representative stages of the care pathway) and input the data requested into the tool. To assess whether the QI tool can be applied in MS centers globally, study sites will be asked to complete a survey following their service evaluation. The survey asks about ease of use of the tool, its usefulness for facilitating local change, relevance of the data captured and key data for repeated use.

Results

Prototype II has separate spreadsheets for entering information on patients at different stages of the care pathway; fields are tailored to the different patient populations so there is less data to input per patient. Data validation programming prevents the insertion of invalid information. To assist MS centers in analyzing their findings, improved visual summaries of clinic-level and patient-level results are generated within the tool; these auto-populate when the required fields in the data input spreadsheets are completed. Prototype II will also support future language translations. More than 18 MS centers have so far expressed interest in trialing prototype II of the QI tool; preliminary insights from selected study sites will be presented.

Conclusions

Following further refinements, widespread roll-out of the QI tool will enable MS centers to collect data to benchmark their clinical standards and to support service improvement.