PNH carries a high disease burden despite treatment

Paroxysmal nocturnal haemoglobinuria (PNH) carries a substantial disease burden and healthcare resource utilization, even in patients already receiving treatment with C5 inhibitors, according to an expert who presented at EHA 2023.

PNH is a rare, chronic, debilitating disorder that most frequently presents in early adulthood and continues throughout the patient’s life. The name of the disease itself describes the clinical consequence of red blood cell breakdown with the release of haemoglobin into the urine. The triad of haemolytic anaemia, pancytopenia, and thrombosis makes PNH a unique clinical syndrome.

Dr Jamile Shammo from Northwestern University in Chicago, Illinois, US and colleagues conducted a retrospective, observational study of 1,138 patients 18 years and older with a diagnosis of PNH. PNH-related hospitalization, treatment response, and signs of anaemia were assessed. [EHA 2023, abstract P796]

The median patient age was 56 years; 59 percent were female. Sixty-seven percent of patients in the cohort had PNH with bone marrow failure. Twenty percent had classic PNH, and 14 percent had unclassified PNH subtypes.

In the year prior to receiving a PNH diagnosis, 52 percent of patients had at least one hospitalization. The median haemoglobin level at baseline was 11 g/dL. Fifty-two percent had anaemia.

Hospitalization, transfusion after 2 years

After a median of 2.6 years of follow-up, 54 percent of patients experienced at least one hospitalization and 21 percent required at least one transfusion. Lower haemoglobin level at baseline was associated with a higher hospitalization rate, longer hospital stays, and higher transfusion rate. Anaemia was linked to higher rates of hospitalization and transfusion.

Fourteen percent of patients received C5 inhibitors. “Despite the well-established efficacy of C5 inhibitors, we found that residual anaemia and haemolysis still affect many PNH-treated patients. In fact, 71 percent remained anaemic after 1 year of treatment,” Shammo shared. “Thirty-six percent still required supported treatment such as transfusion during the follow-up period.”

Fifty-eight percent of patients receiving C5 inhibitors progressed to bone marrow failure. Worse, 29 percent had evidence of intravascular haemolysis, 34 percent had extravascular haemolysis, and 29 percent had breakthrough haemolysis.

Significant unmet needs

“Our analysis points to the importance of anaemia at baseline, which we found to be associated with higher rates of hospitalization and transfusions,” Shammo said. “Importantly, there is an urgent need to address PNH disease burden and develop therapies aimed at improving anaemia, reducing transfusion burden, and improving quality of life of these patients largely affected by extensive treatment requirements.”

PNH can cause death in about 50 percent of affected individuals due to thrombotic complications. Until recently, there is no specific therapy for PNH.

“C5 inhibitors target underlying intravascular haemolysis in PNH. However, they do not address extravascular haemolysis, resulting in sub-optimal response,” explained Shammo. “Despite treatment, some patients still experience anaemia with debilitating fatigue and require transfusions for breakthrough haemolysis episodes.”