KEY TAKEAWAYS
- The phase 4 ActIVe study (NCT04400487) evaluated the effects of voxelotor on physical activity, fatigue, and sleep quality in patients with sickle cell disease (SCD).
- The primary aim of the ActIVe study was to examine the impact of voxelotor, a sickle hemoglobin polymerization inhibitor, on physical activity, fatigue, and sleep quality in SCD.
- The ActIVe study suggests that voxelotor may improve the quality of life in SCD patients by increasing physical activity, reducing fatigue, and improving sleep quality.
Voxelotor is a sickle hemoglobin polymerization inhibitor approved for treating sickle cell disease in patients aged 4 years in the United States and the United Arab Emirates. It has marketing authorization in the European Union, Great Britain, Oman, and Kuwait for patients aged 12 years. Voxelotor has been shown to increase hemoglobin (Hb) and decrease markers of hemolysis; however, its effect on quality of life (QOL) is not entirely understood.
In this study, the researchers aimed to examine the impact of voxelotor on physical activity, fatigue, and sleep quality in SCD patients. Participants with SCD and chronic anemia (Hb 8.0 g/dL at screening) received 1500 mg of voxelotor daily for 24 weeks. Hb was measured at baseline, weeks 2, 12, and 24. Actigraphy wristbands were used to assess activity and sleep from baseline to week 24 continually and were required to be worn for 18 hours per day for 8 consecutive days every 2 weeks. The National Institutes of Health Patient-Reported Outcome Measurement Information System 43 (PROMIS-43) was used to evaluate patient-reported outcomes in adults (aged >17 years) and adolescents (aged 17 years); responses deemed meaningful were interpreted at the group level as a 5-point change from baseline (CFB) in PROMIS domains. All participants provided their informed consent/assent.
Ten sites in the United States enrolled 25 patients with a mean (SD, range) age of 25.0 (12.05, 12-51) years; 64% were female, and 92% were Black or African American. The median(range) duration of voxelotor treatment for patients was 22.3 (2.4-25.7) weeks. At week 24, the mean (SD) CFB in Hb was 0.72 (1.21), and 23 of 25 patients (92%) demonstrated an increase in Hb at some point during the study. The CFB in moderate or vigorous activity (defined as 3 metabolic equivalents of task) over 22 weeks, with a median numerical increase of 13.6 min/day (17.0%) from weeks 20 to 22 (n=17 patients who donned the actigraphy device) was seen. During weeks 20 to 22, the median CFB percentage increase in total daily physical activity was 3.8%. At weeks 20 to 22, whole wake time after sleep onset decreased numerically, with a mean (SD) CFB of –9.9 (47.12)min/day (–2.0% [37.8%]).In 11 adults who completed PROMIS measurements at week 24, clinically significant CFB values were observed for fatigue (mean CFB [SD] of –6.9 [5.86]; 6/11 patients with 5-point CFB) and pain interference (mean CFB [SD] of –5.7 [5.66]; 6/11 with 5-point CFB). In addition, sleep disturbance decreased by 5 points in 4/11 patients (mean [SD]: 1.9 [8.06]).
The results of the ActIVe study indicate that voxelotor-treated patients may experience an improvement in QOL, including an increase in physical activity, a decrease in fatigue, and a reduction in wake time after sleep onset. The study was limited by the small number of participants, the low response rate to quality of life (QOL) questionnaires, and the variable use of the wrist-worn actigraphy device. There is a need for additional research on the effects of voxelotor on QOL, including physical activity and sleep quality.
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT04400487
Nirmish Shah, Clark Brown, Biree Andemariam, Modupe Idowu, Alexander Glaros, Robert M. Cronin, Barbara Moehring, Carolyn Hoppe, Sandy Dixon, Brooke Hayward, David M. Purdie, Emily Reihm Meier, Deepa Manwani/ACTIGRAPHY IMPROVEMENT WITH VOXELOTOR (ACTIVE) STUDY: IMPACT OF VOXELOTOR ON PHYSICAL ACTIVITY, FATIGUE, AND SLEEP QUALITY/Inc, M. G. (n.d.). ACTIGRAPHY IMPROVEMENT WITH VOXELOTOR (ACTIVE) STUDY: IMPACT OF… by Nirmish Shah. Library.ehaweb.org. Retrieved July 18, 2023, from https://library.ehaweb.org/eha/2023/eha2023-congress/387612/nirmish.shah.actigraphy.improvement.with.voxelotor.28active29.study.impact.of.html?f=menu%3D16%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2489%2Aot_id%3D27901%2Atrend%3D4016%2Amarker%3D4179
