Queen Mary University London
Neuroscience and Trauma

Author Of 3 Presentations

Clinical Trials Poster Presentation

P0196 - Cladribine to halt deterioration in people with advanced multiple sclerosis (ChariotMS) (ID 585)

Abstract

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.

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Disease Modifying Therapies – Mechanism of Action Poster Presentation

P0382 - Reduction in CUA MRI lesions in the first 6 months of cladribine tablets treatment for highly active relapsing multiple sclerosis: MAGNIFY-MS study (ID 982)

Speakers
Presentation Number
P0382
Presentation Topic
Disease Modifying Therapies – Mechanism of Action

Abstract

Background

The MAGNIFY-MS study (NCT03364036) aims to determine the onset of action of cladribine tablets 3.5 mg/kg over 2 years (CT3.5) in patients with relapsing multiple sclerosis (RMS). Efficacy data from the pivotal trial CLARITY showed that outcomes in CT3.5-treated patients were superior to placebo with regard to number and relative reduction of standardized combined unique active (CUA) lesions over the 96-week trial. Carrying out early and frequent magnetic resonance imaging (MRI) will provide valuable insights into the onset of action of CT3.5.

Objectives

To report on the onset of action of CT3.5 by observing changes in counts of CUA MRI lesions during the first 6 months of the MAGNIFY-MS study.

Methods

MRI scans were performed at screening, baseline, and at months 1, 2, 3 and 6 following CT3.5 treatment on patients with highly active RMS. Differences in CUA lesions between post-baseline periods (period 1, months 1–6, period 2, months 2–6, and period 3, months 3–6) were compared to the baseline period. CUA lesion count was standardized to period length and number of MRIs in a period. A mixed effects linear model was used to account for within pooled centre correlation and adjusted for CUA lesion count during the baseline period, age, and baseline expanded disability status scale (EDSS; >3, ≤3). Type-I-error inflation due to multiple testing was controlled by a gatekeeping procedure.

Results

The full analysis set considered for primary analysis included 270 patients. Reductions in mean CUA count were observed from month 1 onwards compared to baseline; by -1.193 in period 1, -1.500 in period 2 and -1.692 in period 3 (all p<0.0001). In particular, the mean T1 Gd+ lesion counts were decreased from month 2 onwards compared to baseline; by -0.857 at month 2, -1.355 at month 3 and -1.449 at month 6 (all p<0.0001). Sensitivity analysis using negative binomial distribution showed that the treatment effect increased with time measured as lack of CUA in subsequent periods; by 61% in period 1, 77% in period 2, and 87% in period 3 (all p<0.0001). The proportion of patients without any CUA lesions increased in the first 6 months; by 52% in period 1 (p=0.0241), 66% in period 2 (p<0.001), and 81% in period 3 (p<0.001).

Conclusions

MRI was used to assess disease activity in a group of highly active RMS on CT3.5 treatment from one month onwards. Data show an early onset of action on CUA lesions that was significant from month 1 versus baseline, with a treatment effect that increased over the first 6 months.

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Rehabilitation and Comprehensive Care Poster Presentation

P1100 - Identifying gaps in knowledge, skills and confidence among MS specialists to facilitate improved MS care (ID 1178)

Speakers
Presentation Number
P1100
Presentation Topic
Rehabilitation and Comprehensive Care

Abstract

Background

Evidence suggests that healthcare providers specializing in MS (HCP-MS) face an evolving treatment and clinical landscape, with a patient population who requires advanced care to manage the many facets of their condition. In this context, the gaps in knowledge, skill and confidence that may impact HCP-MS’ ability to make clinical decisions and optimize patient care need to be assessed.

Objectives

To assess HCP-MS’ clinical practice gaps and challenges, their associated causes, and impact on the care of people with MS.

Methods

In a mixed-methods study, 333 neurologists and 135 advanced practice nurses in Canada, France, Germany, Italy, Spain, the United Kingdom and the United States were interviewed or surveyed. Qualitative data were analysed thematically. Quantitative data were analysed using ANOVA and Chi-squares for comparison by country, years of experience, practice setting and MS certification status. Results were triangulated with data from the literature.

Results

Qualitative data indicate current guidelines are perceived as insufficient to manage the complex needs of people with MS. Tests of cognitive function are perceived as time-consuming, potentially inaccurate, and should preferably be administered by rehabilitation specialists or psychiatrists. Survey data indicate 42% of neurologists and 61% of nurses have no or only basic skills in administering such tests. A further 44% and 67%, respectively, have no/basic skills interpreting these tests. HCP-MS reported additional factors that may impede clinical decision-making for optimal personalized care. Thirty-nine percent of neurologists (higher in the UK, Canada and Italy, p<.05) and 44% of nurses report no/basic skills integrating patient goals into treatment recommendations. No/basic skills to make decisions about disease modifying treatment (DMT) sequencing was reported by 28% of neurologists and 62% of nurses. Some adverse events were considered challenging: HCP-MS reported no/basic skills identifying (51%) and managing (61%) infections, and no/basic skills identifying (47%) and managing (56%) cardiac issues.

Conclusions

HCP-MS face significant challenges trying to provide best care to people with MS. There appears to be a need to improve skills in cognitive testing, DMT decision-making, treatment monitoring, and patient communication. Professional development activities should focus on the heterogeneity of MS presentations and optimize different competencies required.

Disclosure: This project has been supported by educational funds from Merck KGaA, Darmstadt, Germany.

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Presenter Of 1 Presentation

Rehabilitation and Comprehensive Care Poster Presentation

P1100 - Identifying gaps in knowledge, skills and confidence among MS specialists to facilitate improved MS care (ID 1178)

Speakers
Presentation Number
P1100
Presentation Topic
Rehabilitation and Comprehensive Care

Abstract

Background

Evidence suggests that healthcare providers specializing in MS (HCP-MS) face an evolving treatment and clinical landscape, with a patient population who requires advanced care to manage the many facets of their condition. In this context, the gaps in knowledge, skill and confidence that may impact HCP-MS’ ability to make clinical decisions and optimize patient care need to be assessed.

Objectives

To assess HCP-MS’ clinical practice gaps and challenges, their associated causes, and impact on the care of people with MS.

Methods

In a mixed-methods study, 333 neurologists and 135 advanced practice nurses in Canada, France, Germany, Italy, Spain, the United Kingdom and the United States were interviewed or surveyed. Qualitative data were analysed thematically. Quantitative data were analysed using ANOVA and Chi-squares for comparison by country, years of experience, practice setting and MS certification status. Results were triangulated with data from the literature.

Results

Qualitative data indicate current guidelines are perceived as insufficient to manage the complex needs of people with MS. Tests of cognitive function are perceived as time-consuming, potentially inaccurate, and should preferably be administered by rehabilitation specialists or psychiatrists. Survey data indicate 42% of neurologists and 61% of nurses have no or only basic skills in administering such tests. A further 44% and 67%, respectively, have no/basic skills interpreting these tests. HCP-MS reported additional factors that may impede clinical decision-making for optimal personalized care. Thirty-nine percent of neurologists (higher in the UK, Canada and Italy, p<.05) and 44% of nurses report no/basic skills integrating patient goals into treatment recommendations. No/basic skills to make decisions about disease modifying treatment (DMT) sequencing was reported by 28% of neurologists and 62% of nurses. Some adverse events were considered challenging: HCP-MS reported no/basic skills identifying (51%) and managing (61%) infections, and no/basic skills identifying (47%) and managing (56%) cardiac issues.

Conclusions

HCP-MS face significant challenges trying to provide best care to people with MS. There appears to be a need to improve skills in cognitive testing, DMT decision-making, treatment monitoring, and patient communication. Professional development activities should focus on the heterogeneity of MS presentations and optimize different competencies required.

Disclosure: This project has been supported by educational funds from Merck KGaA, Darmstadt, Germany.

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