100 Years of TTP

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