Category: Archive

Multiple sclerosis has a preclinical phase during which irreversible damage occurs. This phase is typically associated with subtle symptoms and signs that aren’t enough to warrant a diagnosis of MS and we, therefore refer to this as the MS prodrome. Identifying a prodrome is important as it may allow you to diagnose MS earlier. With the emergence of disease-modifying therapies identifying patients in the preclinical phase of the disease provides the potential to improve disease outcomes; the earlier you modify the course of MS the greater will be the impact on the long-term trajectory. In addition, preservation of brain reserve should reduce the inevitable impact that ‘normal ageing’ has on MS outcome over your life.


Helen Tremlett’s group in British Columbia have cleverly used health administrative and clinical databases in Canada, show increased healthcare utilization prior to the development of a first demyelinating event, compatible with MS. The so-called rate ratios increased steadily between five years and one year before the first demyelinating disease claim, which is an indicator that the increase healthcare utilization was due to the MS prodrome. The study findings support other published observations describing an MS prodrome.


It should not be a surprise that physician or neurologist generated codes that were associated with MS included disorders of the central and peripheral nervous system, disorders of the eye and cerebrovascular disease. Hospital and prescription data were poor predictors, however, hospitalizations related to the urinary system or spinal cord diseases, or prescriptions for urinary antispasmodics or anti-vertigo preparations, were associated with 2 to 3-fold higher odds of developing MS in the future.


MS in common with other neurodegenerative diseases also has a latent, or pre-disease, state prior to the preclinical and clinical phases. The latency phase refers to the so-called ‘at risk’ period prior to the onset of focal inflammatory lesions that defines MS pathologically. Migration studies, between areas of high and low prevalence, indicate that from exposure to the putative environmental risk factors and the onset of the disease is somewhere between 10 and 20 years. Similarly, pathological studies indicate that the preclinical phase of MS could potentially be decades. A large Danish series found that approximately a quarter of cases with pathological evidence of MS at post-mortem were never diagnosed with MS in life. Either these subjects had asymptomatic MS or their symptoms were put down to some other ailment.


In general, MS begins before the first clinical attack; the majority of patients presenting with a clinically isolated syndrome (CIS) have older, inactive, lesions on their MRI that does not account for the CIS. Familial studies demonstrate that some siblings, including unidentical and identical twins, have lesions on MRI compatible with demyelination and/or the presence of oligoclonal IgG bands in their CSF; this is despite the majority of these siblings never going onto to develop MS. The MS endophenotype is the term that we use to capture the ‘at risk’, ‘asymptomatic’, ‘prodromal’ and ‘clinical’ phases of MS.


Redefining MS to capture the different phases of the disease should allow us to study the impact of DMTs on both the asymptomatic (radiologically isolated syndrome – RIS) or prodromal phases. Recent studies have demonstrated that even at these earlier stages of MS there is evidence of end-organ or brain damage.


There is an ongoing debate whether, or not, we should extend the diagnosis of MS into this asymptomatic, and now the prodromal, phases of the disease and to offer these people DMTs. I have little doubt about this and hope the next rendition of the McDonald MS diagnostic criteria will extend the diagnosis of MS into the asymptomatic phase of the disease. Redefining when MS begins will allow us to test whether very early intervention in the disease course improves long-term outcome rather than waiting for the disease to become symptomatic.

Högg et al. Mining healthcare data for markers of the multiple sclerosis prodrome. Mult Scler Relat Disord. 2018 Aug 8;25:232-240.


BACKGROUND: Previous studies suggest the existence of a prodromal period in multiple sclerosis, but little is known about the phenotypic characteristics. This study aims to characterize the multiple sclerosis (MS) prodrome using data mining analytics in the healthcare setting.

Chen et al. Effects of multiple sclerosis disease-modifying therapies on employment measures using patient-reported data. JNNP 2018; http://dx.doi.org/10.1136/jnnp-2018-318228

Background: The direct comparative evidence on treatment effects of available multiple sclerosis (MS) disease-modifying therapies (DMTs) is limited, and few studies have examined the benefits of DMTs on employment outcomes. We compared the effects of DMTs used in the previous 5 years on improving the work attendance, amount of work and work productivity of people with MS.

Methods: The Australian MS Longitudinal Study collected data from participants on DMTs usage from 2010 to 2015 and whether DMTs contributed to changes in employment outcomes. We classified 11 DMTs into three categories based on their clinical efficacy (β-interferons and glatiramer acetate as category 1; teriflunomide and dimethyl fumarate as category 2; fingolimod, natalizumab, alemtuzumab and mitoxantrone as category 3). Each DMT used by a participant was treated as one observation and analysed by log-multinomial regression.

Results: Of the 874 participants included, 1384 observations were generated. Those who used category 3 (higher efficacy) DMTs were 2–3 times more likely to report improvements in amount of work, work attendance and work productivity compared with those who used category 1 (classical injectable) DMTs. Natalizumab was associated with superior beneficial effects on patient-reported employment outcomes than fingolimod (RR=1.76, 95% CI 1.02 to 3.03 for increased work attendance and RR=1.46, 95% CI 1.02 to 2.10 for increased work productivity).

Conclusions: Those using the higher efficacy (category 3) DMTs, particularly fingolimod and natalizumab, reported significant increases in amount of work, work attendance and work productivity, suggesting they have important beneficial effects on work life in people with MS.

ProfG    
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We know you are the best value for money health service in the world and that you try your best with limited resources. We want to pledge our support for you and help you make the next 70 years even better. 


At your heart you espouse several principles that are worth remembering and fighting for: 

1. Healthcare is a basic human right
2. Healthcare should be equitable; no matter who you are you should have access to the same level of care
3. Healthcare should be free at the point of access. 

We know your principles are being eroded and people with MS (pwMS) have highly variable access to care across the UK. Variance in MS Services, for example, access to and the prescribing of disease-modifying therapies, have been well documented by the MS Society, MS Trust and the Royal College of Physicians. This has been backed up by new data presented at the recent ABN meeting in Birmingham from the NHS England’s Bluteq database. 

The Dream Team

ProfG    
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People with relapsing-remitting MS can only be treated with ocrelizumab if alemtuzumab is contraindicated or otherwise unsuitable. The latter is a very grey area and will be open to interpretation. My question is how does patient choice taken into account? NICE clearly does not think this is a priority; for NICE cost-effectiveness trumps patient safety and choice.


This appraisal does not refer to the primary progressive indication. If you think ocrelizumab has had a hard time in RRMS it is going to have an even harder time in PPMS. 

ProfG    
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