LDH blood test can gauge fatigue, quality of life in treated patients
LDH levels may help doctors to determine best treatment strategy
An enzyme called lactate dehydrogenase (LDH), which is a marker of red blood cell breakdown, may be used as a proxy measure for fatigue and quality of life in people with paroxysmal nocturnal hemoglobinuria (PNH) who are being treated with Ultomiris (ravulizumab) or Soliris (eculizumab).
That’s according to a new analysis of data from the open-label Phase 3 clinical trial ALXN1210-PNH-301 (NCT02946463), which compared Ultomiris with Soliris in treatment-naïve patients, or those who had never been treated with complement inhibitors.
Because the level of LDH can be determined from a blood sample, it could offer doctors an easy-to-measure marker to help plan the best treatment strategy or find out how well a treatment is working in their PNH patients.
The analysis, “Predictors for improvement in patient-reported outcomes: post hoc analysis of a phase 3 randomized, open-label study of eculizumab and ravulizumab in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria,” was published in the journal Annals of Hematology. The study was funded by Alexion, AstraZeneca Rare Disease, which markets both Ultomiris and Soliris. At the time of the analysis, three of its investigators were employees at the company.
PNH can lead to breakdown of red blood cells
In PNH, red blood cells become liable to an attack by the complement system, a group of dozens of proteins working along with the immune system to protect the body from infection and remove debris from cells and tissues.
The attack causes hemolysis, or the breakdown of red blood cells. As a result, people with PNH may experience symptoms like fatigue, shortness of breath, and pain, which together can take a toll on quality of life.
The ALXN1210-PNH-301 study showed complement inhibitors Ultomiris and Soliris work equally well to lower the need for blood transfusions — a supportive treatment often used to ease fatigue — and to return LDH to a level within the normal range. Both Ultomiris and Soliris also worked equally well to improve patient-reported fatigue and quality of life.
Now, a team of researchers sought to identify what may have driven such improvements in these patients.
Data came from all 246 participating adults, with a mean age of 45.5 years, who were started on Ultomiris or Soliris a median of 3.9 years after receiving their PNH diagnosis; 125 were randomly assigned to Ultomiris and 121 to Soliris.
As a criterion to enter the study, all patients had to have an LDH level that was equal to or greater than 1.5 times the upper limit of normal.
Over a treatment period of 183 days, or about 26 weeks, reductions in LDH were found to be linked to improvements in both fatigue and quality of life.
Fatigue was scored using the Functional Assessment of Chronic Illness Therapy-Fatigue tool, and quality of life using the European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30. In both, the higher the scores, the better.
Patients whose LDH level was less than 1.5 times the upper limit of normal after 183 days of treatment showed better overall improvements in global health scores on both tests compared with those whose LDH level remained at higher levels.
Patients had rapid, sustained increases in scores on both tests
Rapid, sustained increases in the scores on both tests were seen, even though there were no significant changes in the levels of hemoglobin, or the protein in red blood cells that carries oxygen throughout the body.
Younger age, male sex, and reductions in LDH levels from baseline (the study’s start) to day 183 were among the many factors predicting improvements in fatigue scores.
On the quality-of-life test, a low global health score at baseline, reductions in LDH levels, and improvements in hemoglobin levels with transfusions from baseline to day 183 were significant predictors of improvements in global health scores.
Hemoglobin levels alone, however, did not significantly affect the global health scores on either test.
“Understanding key clinical drivers of improvements in [quality of life] and fatigue during C5 [complement] inhibitor therapy is important for developing appropriate management strategies for patients with PNH,” the researchers concluded.