Changes in Hematologic Lab Measures Observed in Patients with Paroxysmal Nocturnal Hemoglobinuria Treated with C5 Inhibitors, Ravulizumab and Eculizumab: Real-World Evidence from a US Based EMR Network

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH), a rare acquired hematologic disorder, can be treated with C5 inhibitors (C5i) such as eculizumab or ravulizumab. This retrospective study is the first to describe real-world treatment patterns and changes in hematologic PNH-monitoring laboratory tests among C5i-treated US patients. Data were extracted from TriNetX Dataworks Network and included patients with a PNH diagnosis between 1 January 2010, and 20 August 2021. Patients were stratified into three cohorts based on their C5i usage: eculizumab, ravulizumab (prior eculizumab), and ravulizumab (eculizumab naïve). Hematological markers (hemoglobin [Hb], lactate dehydrogenase [LDH], and absolute reticulocyte count [ARC]) and relevant clinical events (e.g., breakthrough hemolysis [BTH], complement-amplifying conditions [CAC], thrombosis, infection, and all-cause mortality) were captured any time within 12 months post-index treatment. Of the 143 (eculizumab), 43 (ravulizumab, prior eculizumab), and 33 (ravulizumab, eculizumab naïve) patients, mean age across cohorts was 42-51 years, 55-61% were female, 63-73% were White, and 33-40% had aplastic anemia. Among all cohorts 12 months post-C5i treatment, 50-82% remained anemic, 8-32% required ≥1 transfusion, and 13-59% had BTH, of which 33%-54% had CACs. Additionally, thrombosis was seen in 7-15% of patients, infection in 20-25%, and mortality in 1-7%. These findings suggest many C5i-treated patients experience suboptimal disease control.

Keywords: C5 inhibitors; anemia; breakthrough hemolysis; eculizumab; hematological outcome; hemoglobin; paroxysmal nocturnal hemoglobinuria; ravulizumab; transfusion.

Figure 1

Patient selection. Abbreviations: aHUS, atypical hemolytic uremic syndrome; C5i. C5 inhibitor; EMR, electronic medical record; ECU, eculizumab; MG, myasthenia gravis; NMSOD, neuromyelitis optica spectrum disorder; PNH, paroxysmal nocturnal hemoglobinuria.

Figure 2

Hemoglobin levels from baseline through 12 months of C5 inhibitor (C5i) treatment. Abbreviations: C5i, C5 inhibitor; ECU, eculizumab; IQR LL, interquartile range lower limit; IQR UL, interquartile range upper limit; LLN, lower limit of normal; RAV, ravulizumab; SD, standard deviation. Note: Mean (±SD) hemoglobin levels were graphed. The LLN for hemoglobin was defined as 12 g/dL.

Figure 3

Lactate dehydrogenase (LDH) levels from baseline through 12 months of C5 inhibitor (C5i) treatment. Abbreviations: ECU, eculizumab; IQR LL, interquartile range lower limit; IQR UL, interquartile range upper limit; RAV, ravulizumab; SD, standard deviation; ULN, upper limit of normal. Notes: Mean (±SD) LDH levels were graphed. 1.5 times the ULN for LDH was defined as 360 U/L.

Figure 4

Lactate dehydrogenase (LDH) levels ≥ 1.5 × the upper limit of normal (ULN) from baseline through 12 months of C5 inhibitor (C5i) treatment. Abbreviations: ECU, eculizumab; LDH, lactate dehydrogenase; RAV, ravulizumab; ULN, upper limit normal. Notes: 1.5 times the ULN for LDH was defined as 360 U/L. Due to the small sample sizes, significance testing was not conducted for the analyses, and descriptive analyses were used for comparisons. For a more detailed analysis of LDH, refer to the BTH analysis in Table 3. ^a Number of patients with at least one test during the time period of interest. ^b Number (%) of patients with at least one test result 1.5 times above the ULN.