Wednesday, 23 April 2014

Clinic speak: highly-effective DMTs and immunizations

Vaccinations on highly-effective DMTs; what you need to know. #ClinicSpeak #MSBlog #MSResearch

"This study below shows that MSers treated with natalizumab mount an immune response to both a memory, or recall, vaccine (tetanus) and a new vaccine challenge (keyhole limpet hemocyanin). This information is important to MSers in that they can have vaccines and be confident that they can mount an immune response to the vaccine and hopefully be protected from the relevant infection. Please note this study only looked at so called component, or inactivated vaccines, and not live vaccines. Live vaccines are composed of live attenuated viruses and require the virus to cause and active infection within the body for the immune system to respond. Examples of live vaccines include the oral polio vaccine and yellow fever. I am not aware of any data on live vaccines and natalizumab treatment and would advise against them. These viruses are neurotropic and hence infect the nervous system.  If the do infect the nervous system you need your immune system to be intact to be able to find and attack the virus. We know that natalizumab prevents the trafficking of lymphocytes into the brain and spinal cord and hence your immune system will not be able to seek and destroy the virus. For similar reasons I warn MSers under my care about travel to places that are associated with exotic infections  that can infect the brain that cannot be covered by a inactivated or component vaccine; examples include dengue fever and yellow fever."

"Do the other high efficacy agents have the same effect on vaccination? Fingolimod blunts your recall and novel immune response to component vaccines. Live vaccines are contra-indicated if you are on fingolimod. With alemtuzumab vaccinations are contra-indicated until 3 months after the last course of treatment and your blood counts have recovered enough to mount an immune response. Some preliminary data (abstract below) suggests that immune responses to both component and live vaccines post-alemtuzumab are intact. This is not surprising as once your immune system recovers post-alemtuzumab it is capable of mounting an immune response. Confirmatory data on vaccination post-alemtuzumab is required as the study below is very small." 

"I personally think immune responses to vaccinations is one factor that needs to be considered when choosing a therapy; this is particularly important for MSers who like to travel. You may also want to delay starting a treatment until you have had specific vaccines. If you have any specific queries regarding vaccinations and the treatment you are on you should discuss this with your neurologist."


J Neurol Sci. 2014 . pii: S0022-510X(14)00193-2.

Background: Natalizumab is an immunomodulatory drug approved for the treatment of MS. 

Objective: This randomized, multicenter, open-label study evaluated natalizumab's effects on immunization responses to a recall antigen (tetanus toxoid [TT]) and a neoantigen (keyhole limpet hemocyanin [KLH]) in RRMSers. 

Methods: Natalizumab-naive relapsing MSers were randomized (1:1; n=30 per group) to receive TT and KLH immunizations either without natalizumab treatment (control) or after 6 months of natalizumab treatment (natalizumab group). An adequate response to immunization was defined as an increase to at least twofold in specific serum immunoglobulin G (IgG) 28days after the first immunization. 

Results: All evaluable MSers achieved protective levels of anti-TT IgG antibodies, and the proportion of responders to this recall antigen, as well as to primary immunization with KLH, was similar in the presence and absence of natalizumab. 

Conclusion: This indicates that natalizumab treatment does not appear to affect responses to primary or secondary immunization in a clinically meaningful way.


McCarthy et al. Immune competence after alemtuzumab treatment of multiple sclerosis. Neurology. 2013 Sep 3;81(10):872-6.

OBJECTIVE: To determine the immunocompetency of patients with multiple sclerosis treated with the lymphodepleting humanized monoclonal antibody alemtuzumab.

METHODS: In this pilot case-control study, we assessed immunocompetence in 24 patients after alemtuzumabtreatment by measuring antibody responses to 3 vaccines (diphtheria, tetanus, and poliomyelitis vaccine, Haemophilus influenzae type b and meningococcal group C conjugate vaccine, and pneumococcal polysaccharide vaccine). In 20 patients, antibodies to common viruses (mumps, rubella, varicella-zoster, and Epstein-Barr virus) were measured before alemtuzumab treatment, then at 1 and 9-11 months after treatment. Results were compared with well-defined historical controls.

RESULTS: Serum antibodies against common viruses remained detectable after treatment, and vaccine responses were normal to T-cell-dependent recall antigens (tetanus, diphtheria, and polio), a T-cell-dependent novel antigen (meningococcus C), and T-cell-independent antigens (pneumococcal). There was no evidence for a diminished response to vaccinations in 5 patients studied within 6 months of alemtuzumab treatment.

CONCLUSION: In this small historically controlled pilot study, we demonstrated i) retained humoral immunologic memory (in the form of antibodies against common viruses and response to recall antigens), and ii) the retained ability to mount a humoral immune response against a novel antigen after treatment with alemtuzumab.

CLASSIFICATION OF EVIDENCE: This pilot study provides Class III evidence that patients with relapsing-remitting multiple sclerosis appear immunocompetent after treatment with alemtuzumab.

Other posts of interest

30 Jul 2013
METHODS: The 2011/2012 seasonal influenza vaccine (containing H1N1, H3N2, and B strains) was administered to patients with relapsing forms of multiple sclerosis (RMS) treated for ≥6 months with teriflunomide 7 mg (n ...

21 Jun 2012
The mechanism of action of natalizumab has immunosuppressive properties and it is not yet investigated if treatment with natalizumab affects the immunological response to vaccination. This study aims to investigate the ...

26 Jun 2013
The authors conclude that vaccination response is not lost post-alemtuzumab treatment and immunity remains if you have been vaccinated previously. However the numbers are small, and so it is difficult to draw wide ranging ...

1 comment:

  1. Here we are talking about vaccination during natalizumab, but what about vaccination before the terapy? I assume this is safe...
    What about if I had BCG one month ago?


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