With rare disease day approaching, this is a good time to discuss the first 100 years of
TTP. The first case of TTP was reported in 1924; however, there was little
known about the disease with no successful treatments until 1991. As such, for 67
years, TTP patients had a 90% mortality rate.
The good news is we have made incredible progress in the last 33 years.
In 1991 the
CanadianApheresis Study Group concluded that plasma exchange (or plasmapheresis) is
more effective than plasma infusion in the treatment of TTP. The use of plasmapheresis
dramatically reduced to less than 10% mortality rate. Over the years, fresh
frozen plasma was replaced by solvent detergentplasma, to reduce plasma side effects on TTP patients.
Since 1991,
we have had four major benefits to allow TTP to be monitored, prevent relapse
and for treatment:
- ADAMTS-13 enzyme was
discovered. If the ADAMTS-13 enzyme has less than 10% activity, then it is
generally concluded the patient has TTP. Measurement of ADAMTS-13 activity is
also used for forecasting a TTP occurrence. A low measurement may justify to a
hematologist that measures should be taken to increase ADAMTS-13 activity. Note
in the US, Fast4TMA can provide ADAMTS-13 activity testing to any US patient at their home with results
in about 24 hours.
- Rituximab wasconcluded as a first line treatment for TTP. The use of rituximab will
increase the ADAMTS-13 activity. For a patient with a case of TTP, rituximab
will help to stop the TTP symptoms. For a chronic TTP patient, rituximab can be
used to increase ADAMTS-13 activity to prevent or delay a TTP recurrence. Although
a first line treatment, availability of rituximab can be an issue as the drug
is considered is off-label for TTP patients, since it was not approved for treatment
of TTP from an organization such as Health Canada or US FDA. Nevertheless, rituximab
is widely used to treat TTP, so hopefully availability issues will be reduced.
- Caplacizumab
is a drug which will reduce TTP symptoms and allow more time to treat TTP. A study concluded
treatment with caplacizumab provided a faster normalization of the platelet
count, a lower incidence of TTP-related death, and lower recurrence of TTP. The
patient presentation of TTP is urgent since an untreated patient has a 90%
mortality rate. This may not be an issue if the patient arrives at the hospital
early with minor symptoms, the doctors immediately diagnose TTP and the patient
reacts well to plasmapheresis. The issue is with patients who do not seek diagnosis
early, it may take a long time for diagnosis, the facility may not perform
plasmapheresis and the patient may be slow to respond to treatments. Use of
caplacizumab for all TTP patients will save lives, suffering and other costs
such as hospital bed/ICU time, treatment time and plasma use.
- RecombinantADAMTS-13 protein designed to address an unmet medical need in people with
congenital TTP (cTTP) by replacing the deficient ADAMTS13 enzyme. It has not
yet been approved to treat acquired TTP (aTTP). The protein can be provided at
home or in a clinic and allows the ADAMTS-13 activity to increase without plasmapheresis.
Hopefully studies will conclude this protein can be provided to aTTP patients. This
could be a game changer.
I’m hoping my
message to TTP patients is that our world is getting better. Plasmapheresis lowers
our mortality rate to below 10%, but we now have treatments which may remove
the stress of plasmapheresis. Hopefully these treatments will be made available
to all TTP patients.
Thanks,
Bruce.
@BruceFightsTTP
