Clinic speak: alemtuzumab does not affect immune competence in MSers

The immune system seems to be fine after alemtuzumab. #MSBlog #MSResearch #ClinicSpeak

"Several MSers have expressed their concerns about the long-term effects of alemtuzumab on their immune systems. Why? Alemtuzumab works by depleting your immune system and allowing it to recover spontaneously. Alemtuzumab kills or bursts open white blood cells or leukocytes by binding to a specific protein CD52 on the surface of the cell. When alemtuzumab binds to the cells it attracts a large number of other proteins, called complement, to the surface of the cells and these proteins pierce a hole in the cell causing it to burst. Complement is the family of proteins the immune system uses to kill damaged or cancerous cells and invading organisms. When the white cells burst they release their contents into the bloodstream; some of these substances are proteins that mediate the effects of inflammation on the body, which is why alemtuzumab causes an infusion reaction with a raised temperature, chills, rigors and a skin rash in most treated MSers. To dampen down the infusion reactions we pretreat MSers who are about to receive alemtuzumab with steroids, paracetamol and anti-histamines."

"Alemtuzumab is given as short courses on a yearly basis; daily for 5 days in the first year and then daily for 3 days in the second and subsequent years. Subsequent courses are only given if your MS has been shown to reactivate, i.e. you have relapses or develop new or enhancing lesions on MRI. The majority of MSers (two-thirds) only require 2 courses to go into long-term remission. A minority of MSers will require 3, 4 or very rarely 5 courses of alemtuzumab. Please note that reactivation of your MS after alemtuzumab does not mean that you have failed to respond to alemtuzumab it simply means you need another course, this is different to maintenance therapies (give continuously) were disease reactivation is an indication of non or suboptimal response."

"After each course the white cells recover by dividing or proliferating. When the immune system recovers there have been questions about whether or not it is competent to fight infections, cancers and whether or not it can remember the vaccines you have had in the past. This study below shows that when the immune system recovers post-alemtuzumab it is competent and does remember the vaccinations you have had in the past. Another observation that tells us the immune system post-alemtuzumab is competent, or nearly competent, is the lack of so called opportunistic infections in alemtuzumab-treated MSers. I find this data very reassuring."

"There is one caveat; when the white blood cell counts post-alemtuzumab are very low, or have not yet fully recovered MSers are at risk of herpes virus reactivation. Once infected with herpes viruses they persist in the body in a dormant state and can reactivate when the immune system is stressed or compromised. To prevent this from occurring we prescribe prophylactic anti-viral drugs for about 6 weeks to prevent herpes virus reactivation. Despite doing this there is an approximately 1 in 50 chance of developing shingle after alemtuzumab treatment. In the clinical trials the majority of shingles cases were mild or moderate. It is also reassuring to know that shingles responds to anti-viral treatments."

"Someone mentioned in a comment the other day that MSers treated with alemtuzumab are at increased risk of developing secondary cancers. This is not correct. There have been too few MSers treated with alemtuzumab, and the ones who have been treated have been followed for too short a time, to answer this question. Therefore the cancer risk is a theoretical risk at present. In my opinion the cancer risk is low as we have not seen any indicator cancers, those cancer associated with drugs that target the immune system, in any of the MSers treated with alemtuzumab in the trials."

"The one risk from being treated with alemtuzumab is well-defined is secondary antibody-mediated autoimmune diseases that occur months to years after the last course of alemtuzumab. Autoimmune thyroid disease is the commonest disease and occurs in ~30% of treated MSers. The second most common is immune mediated thrombocytopenia, or ITP, that occurs in 2-3% of treated subjects. In ITP the immune system destroys the platelets or cells that help stop bleeding. A much more rare disease is so called Goodpasture's disease when the immune system makes antibodies that can damage the kidney. This last two diseases can be serious, but if detected early and treated most people make an unremarkable recovery. These autoimmune complications of alemtuzumab are why MSers who have been treated with the drug need to be monitored with monthly blood and urine tests for at least 4 years after the last course of treatment. Therefore if you are eligible for alemtuzumab and you want to be treated with this drug you are going to have to be adherent to the monitoring programme. If not and MSers die or have near-death experiences from these treatable complications the regulatory authorities may restrict alemtuzumab's use in the future.  This would be unfair on those MSers who may wish to be treated with the drug in the future."

"The real advantage of alemtuzumab is the fact that it is an induction therapy; i.e. you get treated with the drug and you don't have to have it continuously. This has advantages for MSers who can't tolerate daily injection or oral therapies. Another advantage is the long-term remission that the majority of MSers go into after a two courses. Woman wanting to fall pregnant and start a family will find this attribute of the drug very appealing. What has been played down is that a large number of MSers who have disabilities find that they improve spontaneously after alemtuzumab. I don't think this is because alemtuzumab is a neurorestorative drug, but it simply reflects that when you suppress and stop inflammation in the brain and spinal cord you allow spontaneous recovery to occur. This is why I don't believe we need drugs to promote remyelination in MS; remyelination will occur spontaneously if we suppress inflammation with sufficiently effective therapies; a similar observation occurs with natalizumab or Tysabri. An important point regarding the spontaneous improvement post-alemtuzumab is the observation that it is more likely to occur early in the course of the disease, before the demyelinated axons die and there is sufficient reserve capacity to allow recovery. You can't remyelinate an axon that is not there; and this is why alemtuzumab has not be as effective in MSers in with secondary progressive MS."



Epub: McCarthy et al. Immune competence after alemtuzumab treatment of multiple sclerosis. Neurology. 2013 Aug 7.

OBJECTIVE: To determine the immunocompetency of MSers treated with the lymphodepleting humanized monoclonal antibody alemtuzumab.


METHODS: In this pilot case-control study, we assessed immunocompetence in 24 MSers after alemtuzumab treatment 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 MSers, 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 MSers studied within 6 months of alemtuzumab treatment.

CONCLUSION: In this small historically controlled pilot study, the investigators' 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 or antibody immune response against a novel antigen after treatment with alemtuzumab.

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

CoI: multiple

Other alemtuzumab posts of interest:

26 Jun 2013
While treatment of multiple sclerosis patients with alemtuzumab results in marked depletion of lymphocytes from the circulation, it has not been associated with a high incidence of serious infections. In a human CD52 ...
28 Jun 2013
It means that we will have the option of using Alemtuzumab in MSers with relapsing disease who are active. This means it can be used as a first line agent and it won't only be limited to MSers with highly active MS. This means ...
15 Jun 2013
"As you can see from the 4 studies below Alemtuzumab (aka Campath or Campath-1h) has a positive effect on brain atrophy, when compared to interferon-beta. It slows the rate of brain shrinkage. In addition it has a positive ...
29 Jun 2013
"Some of you will be asking, after the euphoria of yesterday,how will Alemtuzumab play out in the field? This will depend on a risk benefit assessment; the risks of the drug, the benefits of the drug and the risk of having MS.

30 Jun 2013
You can see that you are more than twice as likely to remain stable or improve in disability when treated with Alemtuzumab compared to interferon-beta. This refers to 2 years follow-up. However, we know that in the vast ...
29 Jun 2013
CCSVI or Alemtuzumab/Campath: which has the longest tail? "An interesting comparison between CCSVI and Alemtuzumab/Campath. Some of you,as I may find studying search volumes interesting." ...
31 May 2013
An immunological laboratory-based study to assess natural-killer status post-Alemtuzumab treatment will start shortly at Barts and The London site soon. The principal investigator is Dr Ute-Christiane Meier in our group.
08 Mar 2013
MSers with untreated, early, RRMS (McDonald, n = 334) were randomized 1:1:1 to subcutaneous interferon beta-1a (IFNB-1a), or alemtuzumab 12 mg or 24 mg. Visual contrast sensitivity was measured for each eye at ...

21 Mar 2013
"My second poster at the AAN today. This shows that compared to interferon-beta, alemtuzumab treatment more than doubles your chances of noticing some improvement in neurological function." ...
12 Feb 2013
#MSBlog: Alemtuzumab increases your chances of sustained or confirmed disability improvement compared to interferon-beta. "Apologies for putting this poster up so late; it is from the Neuroimmunology Meeting in Porto a ...
03 Dec 2012
Alemtuzumab is a humanized monoclonal antibody that is administered daily for 5 days, and then no further therapy is required for 12 months. It causes rapid and prolonged lymphocyte depletion; the consequent homeostatic ...
01 Nov 2012
Cole et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. The Lancet, Early Online Publication, 1 November 2012 ...

26 Mar 2012
OBJECTIVE: To report the long-term safety and efficacy results from CAMMS223 comparing alemtuzumab with interferon β-1a in early, active relapsing-remitting multiple sclerosis (RRMS). What are the long-term effects of ...
08 Nov 2012
The purpose of the CAM-THY trial is to try and prevent side effects of alemtuzumab (formerly known as Campath-1h). Although alemtuzumab is an effective treatment of MS, it has side effects; in particular 1 in 3 MSers develop ...
28 Oct 2012
"The aim of this presentation was to present the phase 3 trial data on Alemtuzumab in early RRMS as a therapeutic strategy that probably works by depleting circulating lymphocytes. The slides may be a little complicated as ...
28 Aug 2012
In response to a comment yesterday about alemtuzumab being a social phenomenon I did some on-line research using Google Trends to compare alemtuzumab to CCSVI. Methods: I used the search terms alemtuzumab, ...

20 Aug 2012
This means that alemtuzumab will no longer be available as a licensed product in the UK once existing supplies run out. This action is not being taken for any reasons related to product safety, efficacy or supply, but as part of ...
21 Aug 2012
"Yesterday's post on the withdrawal of alemtuzumab to prevent off-license use of the oncology version of alemtuzumab (Mabcampath) resulted in a flurry of discussion and criticism. With some of the latter occurring off-line.
20 Jan 2012
As you know alemtuzumab or campath-1h has remarkable efficacy in relapsing MS. In clinical trials and off-label use in MS, alemtuzumab has been administered intravenously (IV). Alemtuzumab is approved for chronic ...
20 Dec 2012
OBJECTIVE: Alemtuzumab is potentially a highly effective treatment for relapsing multiple sclerosis (MS) acting via complement-mediated lysis of circulating lymphocytes. Variability in post-treatment lymphocyte recovery time ...

13 Apr 2012
Research: Alemtuzumab (formerly known as campath) limits Brain damage. Epub ahead of print: Button et al. Magnetization transfer imaging in multiple sclerosis treated with alemtuzumab. Mult Scler. 2012 Apr 5.
30 Jul 2011
"What is alemtuzumab? You may know the drug as Campath-1h. This is a powerful immuno-modulator that is given as a course of intravenous infusions. It depletes the immune system and allows it to recover. I refer to it as an ...
01 Nov 2012
University of Cambridge news: New MS drug proves effective where others have failed.... Nature News Blog: MS treatment shows success in clinical trials...... Lancet editorial: Alemtuzumab for multiple sclerosis.
27 Aug 2012
It put back the cladribine application 6 months in the US and delayed the FDA decision until after the EMA decision. I believe the negative EMA decision affected the FDA's decision. Let's hope that Alemtuzumab does not go ...

03 Oct 2011
In a phase 2 clinical trial of annual alemtuzumab for the treatment of relapsing-remitting MS, 6/216 (2.8%) patients developed immune thrombocytopenia (ITP). "Thrombocytes or platelets are the cells in the blood responsible ...
21 Nov 2012
Results: Clinical and surrogate markers of inflammation were suppressed. In both the RR and 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 ...
18 Jul 2011
"This was not a negative study; Alemtuzumab is still a very promising disease-modifying therapy! The patients in this trial were less active than previously therefore the trial lacked power to detect a difference in relation to ...
05 Sep 2012
Survey results: alemtuzumab's market withdrawal. "It is clear that the majority of MSers who completed this survey disagree with Genzyme's decision and strategy to withdraw Alemtuzumab from the market." "The depressing ...

11 Jul 2011
A press release on the headline results of the Alemtuzumab vs. Interferon-beta-1a trial: "Sanofi said Lemtrada worked better than an older drug, Rebif, in preventing relapses, as patients treated with Lemtrada were 55 percent ...
11 Sep 2011
"Based on its superior efficacy Alemtuzumab should command a premium price. However, the cost will affect its cost-effectiveness and its license in the UK under NICE. Ideally we would like to use Alemtuzumab in early MS; ...
11 Jun 2012
"My slides from my presentation at the European Neurological Society Meeting in Prague. The analysis shows that alemtuzumab is more effective than interferon-beta-1a (Rebif) in rendering someone with active MS free of ...
09 Sep 2011
This is more of the same (good) news, with regard to Alemtuzumab. This un-controlled and unblinded study indicates that Alemtuzumab (an antibody that kills white blood cells) quells disease activity in MSers who have ...

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