Dr Catherine Flynn
Consultant Haematologist, TCD Associate Clinical Professor,
St James’s Hospital and Coombe Hospital
Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, life-threatening blood disorder affecting young patients with an average age of 40 years at diagnosis. Men and women are equally affected.
There are over 50 patients living with PNH in Ireland. Patients can present with severe fatigue related to anaemia (low haemoglobin), infections or bleeding symptoms caused by bone marrow failure. They may also present with blood clots.
Cause and effect of paroxysmal nocturnal haemoglobinuria
PNH is caused by the acquisition of a mutation in the PIGA gene in blood stem cells, resulting in mature blood cells losing proteins that protect them from the complement system. The consequences are continuous destruction of red cells in circulation, causing anaemia, and jaundice.
Diagnosis can be difficult as anaemia, jaundice and blood thrombosis (clotting) can be caused by many conditions. Once the diagnosis is considered, however, a haematologist can arrange a specific blood test to confirm the diagnosis.
Classic PNH and other blood diseases
PNH can overlap with other blood conditions, including autoimmune or inherited bone marrow failure syndromes and myelodysplasia. Optimal treatment pathways will depend on a careful investigation of an individual’s blood and bone marrow. Those with ‘classic’ PNH with red cell breakdown, jaundice and, sometimes, thrombosis need urgent consideration for anti-complement medication.
Eculizumab is the only anti-complement therapy available in Ireland outside of a clinical trial and is extremely expensive. It is accessed through the National Centre for Pharmacoeconomics (NCPE), but there are strict criteria to be met prior to approval.
New, expensive drugs making a difference
During 2011 and 2016, studies demonstrated that eculizumab treatment has increased the five-year survival for PNH patients to >90%, revolutionising the outcome for PNH patients. Previously, one-third of patients would not survive more than five years from diagnosis due to complications. Eculizumab infusions are considered lifelong treatments, administered at home every two weeks.
Optimal treatment pathways will depend on
a careful investigation of an individual’s
blood and bone marrow.
Treatment does not mean cure
While complement inhibitor treatment improves survival, it is not a cure. Patients require lifelong monitoring. Intravenous eculizumab is time-consuming for patients and often inconvenient. Frequent medical visits are required for treatment of associated infections, regular vaccination and monitoring for silent clotting and associated heart, lung, liver and kidney disease. Moreover, PNH can evolve into other blood conditions, and continued surveillance is required.
Emerging treatment options for PNH
Access to eculizumab is not easy in Ireland due to cost and the strict criteria used to determine patient eligibility. However, many new complement-blocking treatments are on the horizon for Irish patients. These include biosimilar preparations of eculizumab — which are less expensive — and longer-acting preparations such as ravulizumab — which can be given every eight weeks, giving patients more freedom.
A self-administrated complement inhibitor is in the clinical trial phase (Commodore-1) and is actively recruiting Irish PNH patients who are still anaemic on eculizumab. This medicine hopes to allow more independence for patients, as it only requires administration every four weeks. Newer agents, which inhibit the complement pathway at different points, are going through the approval processes of the NCPE and are sometimes available in exceptional cases.
What’s the price of living a normal life?
For Irish patients with this chronic rare condition, the only curative treatment is a bone marrow transplant — a procedure carrying significant risk. For most patients and haematologists, it is a last resort.
Many patients who live with this chronic condition seek a long-term solution, which will allow them to live comfortably. The approval pathway for new drugs is challenging, and these new medications are all costly. Our healthcare system continues to face the economic challenges of expensive medications, and haematologists continue to advocate for our PNH patients who want to live a ‘normal’ life.