Overview of Lemtrada treatment, side effects, benefits

1. Lemtrada is one of the most effective MS therapies we have and the only induction therapy on the
table. I rate its clinical efficacy as being in the same zone as natalizumab (Tysabri) and bone marrow
transpolataion (not liscensed as a MS treatment).
Lemtrada offers the advantage of:
1) being an induction therapy over natalizumab (pulse vs. continuous administration)
2) it is safer than BMT
3) Offers the possibility of remyelination by giving the body a break from inflammation, see
below for more on this topic
However, Lemtrada comes with its own relatively unique safety profile that makes most
neurologists, and the FDA, label it as too risky for 1st-line use. I think we need ask ourselves:
1) who should be taking on the risks of Lemtrada as a treatment for MS;
- regulators, neurologists or the MSers themselves?
- I personally believe that if someone with active MS understands their disease and the
risks and benefits of the various treatment options on the table, who am I to deny them
treatment with Lemtrada if they want it as a first-line therapy?
- Surely, it should be about informed decision making and informed consent."
How it Works:
1) Lemtrada's putative mode of action is via depleting your immune system and allowing it to
recover spontaneously.
2) Lemtrada kills or bursts open white blood cells, or leukocytes, by binding to a specific protein
CD52 on the surface of the cell.
3) When Lemtrada 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.
Definition: Complement is the family of proteins the immune system uses to kill damaged or
cancerous cells and invading organisms.
4) When the white cells burst they release their contents into the bloodstream
5) Some of these substances are proteins that mediate the effects of inflammation on the body
- this is why Lemtrada causes an infusion reaction with a raised temperature, chills, rigors
and a skin rash in most treated patients.
- To dampen down the infusion reactions we pretreat patients who are about to receive
Lemtrada with steroids, tylenol and anti-histamines.
Dosing:
Lemtrada 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 Lemtrada.

2. Please note that reactivation of your MS after Lemtrada does not mean that you have failed to
respond to Lemtrada it simply means you need another course
- this is different to maintenance therapies (give continuously- Avonex, Tysabri, orals, etc)
were disease reactivation is an indication of non or suboptimal response.
What happens after the first dose?
After each course the white cells recover by dividing or proliferating.
What are the long term effects on the immune system?
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.
Will I lose Vaccine and Exposure mediated Immunity?
A small study has shown that when the immune system recovers post-Lemtrada it is competent and
does remember the vaccinations you have had in the past.
Another observation that tells us the immune system post-Lemtrada is competent, or nearly competent,
is the lack of so called opportunistic infections in Lemtrada-treated MSers."
Why do Lemtrada treated patients need to take Acyclovir for 4-6 weeks post infusion?
There is one major caveat; when the white blood cell counts post-Lemtrada are very low, or have not
yet fully recovered MSers are at risk of herpes virus reactivation.
Unfortunately, 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 shingles after Lemtrada
treatment. In the clinical trials the majority of shingles cases were mild or moderate. It is also reassuring
to know that shingles can be treated with anti-viral drugs."
Other Risks- Cancer:
Whether or not MSers treated with Lemtrada are at increased risk of developing secondary cancers is at
present unknown. There have been too few MSers treated with Lemtrada, and the ones who have been
treated have been followed for too short a time, to answer this question.
Therefore the increased cancer risk is a theoretical risk at present. In my opinion the cancer risk is low as
we have not seen many of the so called indicator cancers, i.e. those cancers associated with drugs that
target the immune system, in any of the MSers treated with Lemtrada in the phase 3 trials. But on
balance it is too early to make any judgment on this.
Main Risk- Other Autoimmune Disorders
Top 3 being- Thyroid disease, ITP and Goodpastures Disease
The one risk from being treated with Lemtrada is the development of secondary antibody-mediated
autoimmune diseases that occur months to years after the last course of Lemtrada.
Autoimmune thyroid disease is the commonest disease and occurs in ~30% of treated MSers.

3. 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.
These last two diseases can be serious, but if detected early and treated most people make a good
recovery.
Rationale for REQUIRED post-Lemtrada monitoring
These autoimmune complications of Lemtrada 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 Lemtrada and you want to be treated with this drug you are going to
have to be adherent to the monitoring program.
If not and MSers die, or have near-death experiences, from these treatable complications the regulatory
authorities may restrict Lemtrada's use in the future. This would be unfair on those MSers who may
wish to be treated with the drug in the future.
Emma’s note-
This is why I post my labs and are so intent in having them done on time.
It is just plain silly to not follow up with this required monitoring and take unnecessary risks.
Advantages of Lemtrada:
The real advantage of Lemtrada 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.
1) This has advantages for MSers who can't tolerate daily injection or oral therapies.
2) Another advantage is the long-term remission that the majority of MSers go into after a two courses.
3) Woman wanting to become pregnant and start a family will find this attribute of the drug very
appealing. The drug is out of their system in a matter of weeks and will not affect the growing baby if
you wait for the drug to clear before becoming pregnant.
Game Changer: Lemtrada treatment promotes Repair
What has been played down is that a large number of MSers who have disabilities find that they improve
spontaneously after Lemtrada.
- I don't think this is because Lemtrada 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.

4. - 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 early in the disease
course; a similar observation occurs with natalizumab or Tysabri.
- An important point regarding the spontaneous improvement post-Lemtrada 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 Lemtrada has not be as effective in MSers in with secondary progressive MS.