Study Finds Predictors of Response to Ravulizumab, Eculizumab in PNH

Levels of lactate dehydrogenase (LDH), a proxy for intravascular hemolysis (IVH), were significant predictors of fatigue and quality of life outcomes in patients with paroxysmal nocturnal hemoglobinuria (PNH) treated with complement 5 (C5) inhibitors, according to a post hoc analysis of phase III noninferiority study data published in Annals of Hematology.

“Treatment goals, particularly for C5-inhibitor naive patients, should focus on the improvement of LDH levels and subsequent avoidance of IVH, which C5 inhibitors have been demonstrated to successfully achieve,” wrote the study’s lead author, Hubert Schrezenmeier, MD, from the Institute of Transfusion Medicine at the University of Ulm in Germany.

Lactate Dehydrogenase Associated With Fatigue, Quality of Life Outcomes

The analysis included 246 patients with PNH naïve to C5 inhibitors that received ravulizumab or eculizumab. The primary outcomes were LDH and hemoglobin levels. Patient-reported outcomes were evaluated with Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scores for fatigue and European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) scores for quality of life.

Reportedly, improvements in absolute mean LDH levels were significantly associated with improvements from baseline in both mean FACIT-F score (P=.0024) and EORTC QLQ-C30 global health score (P<.0001) at day 183. The authors noted that improvements were produced despite nonsignificant increases in hemoglobin levels.

Ultimately, “understanding key clinical drivers of improvements in [quality of life] and fatigue during C5 inhibitor therapy is important for developing appropriate management strategies for patients with PNH,” Dr. Schrezenmeier and colleagues concluded.

Reference

Schrezenmeier H, Kulasekararaj A, Mitchell L, et al. 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. Ann Hematol. 2024;103(1):5-15. doi:10.1007/s00277-023-05483-0