Thursday, 8 January 2015

Neuroprotective effect of glatiramer acetate

There is still life left in the old horse called glatiramer acetate. #MSBlog #MSResearch

"MRI is the biomarker that correlates with clinical outcomes best in MS and is increasingly being used to assess prognosis, risk stratification, response or non-response to treatment and the effectiveness of DMTs. When you develop a new Gd-enhancing lesion on MRI about 80% of these will leave behind a white scar on a T2 scan; about 1 in 4 T2 lesions are associated with a black-hole on the T1 scans. We know that black hole lesions are more destructive and are associated with greater loss of axons (nerve processes). It is therefore very reassuring to see that the new formulation of glatiramer acetate, not only reduces the number of new lesions but reduces the proportion that are converted to black holes, when compared to placebo. This implies that GA is neuroprotective and is either reducing the inflammation, which causes the damage, or it is protecting the axons in the lesion from degenerating. This will be good news for MSers who on GA and doing well. GA is a very safe drug when used long-term; it is a pity we can't predict who will be a responder to the drug before we start anyone on GA. In my experience the majority of MSers on GA have breakthrough activity and need to be escalated to a more effective DMT within the first 2-4 years. However, the minority who don't have breakthrough activity, i.e. are considered to have no evident disease activity (NEDA), do very well. I hope this study provides some food for thought as many Pharma companies are trying to promote switching to their drugs based on MSers being tired of taking injections. I am sure MSers who are doing well on GA may not want  to change; a reasonable decision that is supported by data such as this."

Epub: Zivadinov et al. Effect of glatiramer acetate three-times weekly on the evolution of new, active multiple sclerosislesions into T1-hypointense "black holes": a post hoc magnetic resonance imaging analysis. J Neurol. 2014.

Background: Conversion of active lesions to black holes has been associated with disability progression in RRMSers and represents a complementary approach to evaluating clinical efficacy. 

Objective: The objective of this study was to assess the conversion of new active magnetic resonance imaging (MRI) lesions, identified 6 months after initiating treatment with glatiramer acetate 40 mg/mL three-times weekly (GA40) or placebo, to T1-hypointense black holes in RRMSers. 

Methods: Subjects received GA40 (n = 943) or placebo (n = 461) for 12 months. MRI was obtained at baseline and Months 6 and 12. New lesions were defined as either gadolinium-enhancing T1 or new T2 lesions at Month 6 that were not present at baseline. The adjusted mean numbers of new active lesions at Month 6 converting to black holes at Month 12 were analyzed using a negative binomial model; adjusted proportions of new active lesions at Month 6 converting to black holes at Month 12 were analyzed using a logistic regression model. 

Results: Of 1,292 subjects with complete MRI data, 433 (50.3 %) GA-treated and 247 (57.2 %) placebo-treated subjects developed new lesions at Month 6. Compared with placebo, GA40 significantly reduced the mean number (0.31 versus 0.45; P = .0258) and proportion (15.8 versus 19.6 %; P = .006) of new lesions converting to black holes. 

Conclusions: GA significantly reduced conversion of new active lesions to black holes, highlighting the ability of GA40 to prevent tissue damage in RRMS.

CoI: multiple

1 comment:

  1. I might have been doing well on GA, but with no routine MRI on the NHS in the UK, I only had my own clinical evidence to go on. Therefore I switched to a more effective front line DMT recently (with worse side effects). Would I have switched with a regular MRI scan? Would GA + regular MRI cost the NHS less?


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