Saturday, 1 February 2014

Clinic Speak: do MSers on DMTs respond to vaccination

Should MSers be vaccinated? #ClinicSpeak #MSBlog #MSResearch

"We know that a least a third of relapses in MSers occur in the so called at risk period after an infection. This is typically defined as the period up to 6 weeks after an infection. In the past we thought viral infections, for example flu, were the only infectious triggers, however, more recently data has emerged implicating bacterial infections (for example urinary tract infections or UTIs) as well. I also suspect that asymptomatic infections may also trigger relapses; these are infections that stimulate the immune system but are not of sufficient intensity to cause any symptoms. An example of an asymptomatic infection would be the reactivation of latent viruses within the body. EBV is a good example of a latent virus. EBV reactivates itself continuously, and results in shedding of the virus in your saliva. Carriers are unaware of when EBV reactivates itself. Why is this important? If we could prevent infections we could reduce the risk of relapses and asymptomatic relapses (MRI activity without associated symptoms), which will reduce damage from focal MS lesions. In addition, infections are known to boost the function of immune cells in the brain and spinal cord, in particular macrophages and microglia, that are though to be involved with disease progression."

"How can we use this information to help MSers? A simply hypothesis is that if we can prevent infections we could reduce infection-triggered relapses. One way of preventing infections is by vaccination. Clearly live vaccinations, i.e. giving a live attenuated virus to induce immunity to a wild-type virus, is the same as having an infection, albeit a milder infection. This is why I have always been very wary about live viral vaccination in MSers. We simply don't have data to know how safe, or unsafe, these vaccines are in MSers. Hence my advice is to avoid live vaccines if you can. However, if the risk of acquiring an infection outweigh the risks of the vaccine you should have the vaccine. The most common scenario I have to give advice on is the live yellow fever vaccine in MSers wanting to travel to areas that have yellow fever. I would estimate that about a third choose to have the vaccine and two-thirds don't; you need to remember that yellow fever is transmitted by a mosquito bite so you can reduce your chances of getting yellow fever by travelling to the relevant country or area in the season when mosquito bites are low, i.e. the non-rainy season, and by taking precautions to prevent mosquito bites (insect repellents, covering-up and mosquito nets). With inactivated component vaccines the risks of triggering a relapse are lower. There is data that the seasonal flu vaccine and the hepatitis B vaccine don't trigger relapses or MRI activity. Based on this I therefore feel more confident about the administration of non-live vaccines in MSers. Please note that if you are on immunosuppressant drugs, for example mitoxantrone, alemtuzumab, fingolimod, teriflunomide, cladribine, etc. live vaccines are contra-indicated. "

"Do MSers respond to these vaccines? Does DMTs impair the immune response to vaccines? The study below suggests that apart from interferon-beta the immune response to the flu vacccine is blunted in MSers on immunomodulatory therapies. This is not surprising given that they interfere with immune function. The investigators recommend that MSers should be tested to see if they have responded to the vaccine and if not given a second dose. In my opinion this not practical, and I doubt cost-effective, for  the 1000's of MSers in our care. Despite this data we will continue to recommend seasonal flu vaccination to all the MSers in our care; the possibility of a response to vaccine with protection against influenza is better than no protection if you were not offered and did not have the vaccine."

"What about bacterial infections? The commonest bacterial infection to inflict MSers is UTIs. This is why I am on a mission to tackle this problem. UTIs are particularly bothersome to MSers and may be causing much more harm than we realise. Not only do they trigger relapses UTIs might drive immune mechanisms that increase the rate of MS progression. This is why it is important for MSers with recurrent urinary tract infections to speak to their MS Team for advice on what can be done to reduce the frequency and severity of UTIs. We are about to launch a research project within our group on this issue; we plan to define the problem with an audit and then test different strategies to reduce the frequency and severity of UTIs. We will keep you posted on the blog about this project."

Epub: Olberg et ak. Immunotherapies influence the influenza vaccination response in multiple sclerosis patients: an explorative study. Mult Scler. 2014 Jan 16.

BACKGROUND: The immunogenicity of influenza vaccines in MSers undergoing immunomodulatory treatment is not well studied.

OBJECTIVES: This explorative study investigated the influence of immunomodulatory treatment on MSers receiving pandemic H1N1 (swine flu) vaccination in 2009 and seasonal influenza vaccination in 2010.

METHODS: We investigated the immune response to pandemic H1N1 vaccination among 113 MSers and 216 controls during the pandemic of 2009. We also investigated the serological response to seasonal influenza vaccination (2010 - 2011 season) among 49 vaccinated and 62 non-vaccinated MSers, versus 73 controls. We evaluated these vaccine responses by haemagglutination inhibition assay.

RESULTS: MSers receiving immunomodulatory treatment had reduced protection (27.4%), compared to controls (43.5%) (p = 0.006), after pandemic H1N1 vaccination (2009). The rates of protection were not influenced by interferon beta treatment (44.4% protected), but were reduced among MSers receiving glatiramer acetate (21.6%), natalizumab (23.5%), and mitoxantrone (0.0%). A similar pattern emerged after MSers received a seasonal influenza vaccination in 2010.

CONCLUSIONS: These findings suggest that MSers receiving immunomodulatory therapies other than interferon beta should be considered for a vaccine response analysis and perhaps be offered a second dose of the vaccine, in cases of insufficient protection.

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