Ravulizumab Boosts Activity Levels, Quality of Life in Patients with PNH

David Dingli, MD, PhD

Credit: Mayo Clinic

Patients with paroxysmal nocturnal hemoglobinuria (PNH) treated with ravulizumab achieved quality-of-life and activity scores within the range of the healthy US general population, including tiredness, sleep, and physical and mental health levels, according to a new study.¹

These results were obtained from the 32-week prospective, observational cohort REVEAL study among eligible individuals with the rare, chronic blood disorder who wore a digital wearable activity-tracking device and reported patient-reported outcome (PRO) data.

“The findings from the REVEAL study show that ravulizumab-treated patients with PNH who achieve good disease control (primarily indicated by lactase dehydrogenase levels within the near-normal range) demonstrate physical and mental health, fatigue, resting heart rate, daily activity, and sleep parameters that are within the range of US general population norms,” wrote the investigative team, led by David Dingli, MD, PhD, department of hematology, Mayo Clinic.

PNH is a progressive and potentially life-threatening blood disorder, characterized by red blood cell destruction and white blood cell and platelet activations.² Symptoms of PNH include fatigue, stomach pain, and difficulty swallowing, impacting the quality of life for a patient.

Ravulizumab is a complement component 5 (C5) inhibitor that is the standard of care for PNH in the US – treatment can reduce thrombosis risk, improve survival and quality of life, and reduce fatigue from the blood disorder.³ However, there are limited data on how the therapy affects sleep patterns, daily activity, and work productivity among individuals with PNH.

REVEAL was designed to evaluate data on resting heart rate, physical activity, and sleep collected via a wrist-worn Fitbit device and PRO data collected via weekly surveys over 32 weeks in adults with PNH on maintenance therapy with ravulizumab or eculizumab.¹

Surveys in the trial included the Functional Assessment of Chronic Illness Therapy (FACIT) – Fatigue, Patient-Reproted Outcomes Measurement Information System (PROMIS) Global Physical Health, PROMIS Global Mental Health, PROMIS Sleep-Related Impairment and Sleep Disturbance, and the Work Productivity and Activity Impairment Questionnaire – Specific Health Problem (WPAI-SHP).

Correlations between activity data on the wearable tracker and PRO scores, including fatigue, sleep, and quality of life, served as the primary endpoints. Exploratory analyses aimed to evaluate these results against the US general population values reported in the available literature.

A total of 28 ravulizumab-treated patients were enrolled in the study, with a median age of 34 years and consisting of 54% female patients. All patients were on an 8-week ravulizumab infusion schedule. Across the 32-week study period, 82% of PRO surveys were completed and returned in the identified timeline.

Overall, PRO scores reported by ravulizumab-treated patients were within the normal range for the US general population. Over 32 weeks, the mean FACIT-Fatigue score (40.0), PROMIS Global Physical Health (51.0), Global Mental Health (51.0), Sleep-Related Impairment (50.0), and Sleep Disturbance (49.0), remained within the general population normative values.

Meanwhile, the average overall work impairment from the WPAI-SHP was 22.0% for ravulizumab-treated patients. For the general population, a WPAI of 17.0% was identified in patients aged 30–39 years.

With a data collection rate of 81% during the study period, wearable activity data showed the mean resting heart rate (67 bpm), daily step count (7476), and sleep duration (7.7 h) remained within the range of the US general population rates. Notably, in patients receiving ravulizumab, a higher number of daily steps showed a weak, but positive, correlation with PROMIS Global Physical and Mental Health scores.

“These findings show that in some instances PRO scores can reflect activity levels in patients with PNH, but further investigation and additional data collection are needed to support this point,” Dingli and colleagues wrote.

References

1. _{Griffiths EA, Min JS, Lee WN, et al. Patient-reported outcomes and daily activity assessed with a digital wearable device in patients with paroxysmal nocturnal hemoglobinuria treated with ravulizumab: REVEAL, a prospective, observational study. Health Qual Life Outcomes. 2024;22(1):62. Published 2024 Aug 9. doi:10.1186/s12955-024-02279-2}
2. _{Schrezenmeier H, Röth A, Araten DJ, et al. Baseline clinical characteristics and disease burden in patients with paroxysmal nocturnal hemoglobinuria (PNH): updated analysis from the International PNH Registry. Ann Hematol. 2020;99(7):1505-1514. doi:10.1007/s00277-020-04052-z}
3. _{Stern RM, Connell NT. Ravulizumab: a novel C5 inhibitor for the treatment of paroxysmal nocturnal hemoglobinuria. Ther Adv Hematol. 2019;10:2040620719874728. Published 2019 Sep 10. doi:10.1177/2040620719874728}