Thursday, 28 August 2014

MS register spots depression and anxiety

Jones KH, Jones PA, Middleton RM, Ford DV, Tuite-Dalton K, Lockhart-Jones H, Peng J, Lyons RA, John A, Noble JG. Physical Disability, Anxiety and Depression in People with MS: An Internet-Based Survey via the UK MS Register.PLoS One. 2014 Aug 25;9(8):e104604.

INTRODUCTION: People with Multiple Sclerosis are known to have a relatively high prevalence of both anxiety and depression. Studies of the relationship between physical disability and mental health in people with MS have reported mixed results, showing the need for further work.
METHODS: Between May 2011 and April 2012, 4516 people completed the MSIS-29 (v.1) and HADS scales via the dedicated internet site of the UK MS Register within a 7 day time window. These responses were linked with basic demographic and descriptive data.
RESULTS: The proportions of people experiencing anxiety or depression increased with physical disability such that 38.0% of respondents with low, and 66.7% with high disability reported at least mild anxiety, and 17.1% of people with low, and 71.7% with high disability experienced at least mild depression.
CONCLUSIONS: This study indicates that there is a positive relationship between physical disability and anxiety and depression, that physical disability impacts on anxiety and depression to differing extents, and that the effects vary with gender, age, disease course and disease duration. We have shown that physical disability is a predictor of anxiety and depression, and that other factors may mask the extent of this effect. It is essential that mental well being is given due attention in caring for people with MS so that all their health needs can be met.


The results are self explanatory however the question is: Have you considered signing up to the MS register (CLICK HERE).

By joining the community of people in the UK affected by MS and contributing to the MS Register, you will be directly involved in generating new research. The knowledge we gain from this study will fuel campaigns for fair, relevant policy and improved healthcare for people living with MS.

Can we speed up the drug development process?

This is an Ebola virus and it is interesting that governments have approved the testing of an relatively-untested drug (it has not had the proper human trials) in people infected with this deadly virus.....However, when it comes to progressive MS, you have to wait until it goes through years of testing before you get a choice of whether you take the risk of a test drug in a trial. Is it time that governments are more inventive to speed the drug development process up? It should suit pharma and could suit you. 

However, should your protection be the primary driver? This is what the current process aims to do?

ClinicSpeak: When to say no to alemtuzumab treatment?

When good intentions turn sour; tipping the risk:benefit scales the wrong way #ClinicSpeak #MSBlog #MSResearch

“When I was a much younger MSologist I recall having to formulate mitoxantrone treatment guidelines for MSers with highly-active MS. At the time we had two competing protocols the monthly Edan protocol, for 6 months, for highly-active MSers who had failed the injectables therapies and the 3 monthly Hartung protocol, for 2 years, for MSers who have active disease with more advanced MS. MSers who were being considered for the 2-year protocol tended to have more advanced MS and tended to be on the cusp of developing secondary progressive MS. One patient taught me how delicately balanced therapeutic decisions can be when using risky therapies such as mitoxantrone in patients with more advanced MS. This particular patient had had a severe spinal relapse and needed a urinary catheter; the intention was this catheter was short-term and would be removed once he had recovered from his relapse. Because his MS was so active I went ahead and prescribed mitoxantrone, which was a mistake. A week later he was admitted urgently to his local hospital with neutropenic (low white blood cell counts) sepsis from a urinary tract infection. He ended up in intensive care unit with septicaemia and septic shock and almost died.”



“The lesson I learned from this unfortunate patient was the urinary catheter had tipped the risk:benefit scale the wrong way. A similar thing may be happening with alemtuzumab. A large number of neurologists that I am meeting across Europe are telling me that they are using Alemtuzumab third-line in patients with advanced MS who sound to me as being on the cusp of  having SPMS. We need to be careful using alemtuzumab in this population. Firstly, the Cambridge group showed almost a decade ago that alemtuzumab is unlikely to make much difference in SPMS, which is why the drug was developed in early RRMS. The baseline criteria for both phase 3 studies targeted early MS (see slide 14 below); disease duration for both studies was low. This is why the European Medicine Agency has given alemtuzumab a liberal 1st-line license; in their opinion the risk:benefit ratio in this population is favourable. At present we don’t know what the risk:benefit ratio is in patients who have had symptomatic MS for more than 10 years and are in the early secondary progressive phase. What we need is controlled phase 3 clinical trials in this phase of the disease to define the benefit:risk ratio. The aim of this study would be to see if alemtuzumab slowed the rate of progression or if there was at therapeutic lag and that MSers did well later on.”

“Why is this issue important? Because a large number of MSers with advanced disease, and/or SPMS, are seeking my opinion regarding alemtuzumab treatment and are going way disappointed, and frustrated, because I won’t agree to treat them with alemtuzumab. In the same way as urinary catheters became a contra-indication to mitoxantrone treatment, clinically progressive MS is a relative contra-indication to alemtuzumab treatment. We simply don’t have data to define whether or not the risks associated with alemtuzumab treatment, the burden of monthly blood & urinary monitoring and the cost of treatment justify the undefined benefits. This is why MSers with advanced MS or SPMS seeking my opinion regarding alemtuzumab treatment need to realise that until I have data to the contrary I will say no to alemtuzumab treatment in this phase of the disease.”





“The following is the paper from Cambridge showing a differential response to alemtuzumab based on disease duration and MS stage.”

Coles et al. The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol. 2006 Jan;253(1):98-108.

Background: From 1991-2002, we treated 58 MSers using the humanised monoclonal antibody, Alemtuzumab, which causes prolonged T lymphocyte depletion. Clinical and surrogate markers of inflammation were suppressed.

Results: In both the relapsing-remitting (RR) and secondary progressive (SP) stages of the illness, Alemtuzumab reduced the annual relapse rate (from 2.2 to 0.19 and from 0.7 to 0.001 respectively; both p < 0.001). Remarkably, MRI scans of SPMSers, treated with Alemtuzumab 7 years previously, showed no new lesion formation. However, despite these effects on inflammation, disability was differentially affected depending on the phase of the disease. SPMSers showed sustained accumulation of disability due to uncontrolled progression marked by unrelenting cerebral atrophy, attributable to ongoing axonal loss. The rate of cerebral atrophy was greatest in MSers with established cerebral atrophy and highest inflammatory lesion burden before treatment (2.3 versus 0.7 ml/year; p = 0.04). In contrast, RRMSers showed an impressive reduction in disability at 6 months after Alemtuzumab (by a mean of 1.2 EDSS points) perhaps owing to a suppression of on-going inflammation in these MSers with unusually active disease. In addition, there was a further significant, albeit smaller, mean improvement in disability up to 36 months after treatment. 

Conclusion: We speculate that this represents the beneficial effects of early rescue of neurons and axons from a toxic inflammatory environment, and that prevention of demyelination will prevent long-term axonal degeneration. These concepts are currently being tested in a controlled trial comparing Alemtuzumab and IFN-beta in the treatment of drug-na├»ve MSers with early, active RRMS.

CoI: multiple