Fatigue, symptom burden, and health‐related quality of life in patients with myelodysplastic syndrome, aplastic anemia, and paroxysmal nocturnal hemoglobinuria

Escalante, Carmen P.; Chisolm, Stephanie; Song, Juhee; Richardson, Marsha; Salkeld, Ellen J.; Aoki, Etsuko; Garcia‐Manero, Guillermo

doi:10.1002/cam4.1953

Cited by 42 publications

(48 citation statements)

References 28 publications

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“…Patients with PNH report severe fatigue, 20 and treatment with eculizumab is associated with significant improvements in the FACIT-Fatigue scale and EORTC QLQ-C30 subscale scores. 6,8 Because patients were required to be clinically stable on eculizumab before study entry, FACIT-Fatigue scores were relatively high at baseline (ravulizumab-ravulizumab, 43; eculizumab-ravulizumab, 41; range, 0-52; high scores indicate less fatigue).…”

Section: Discussionmentioning

confidence: 99%

One‐year outcomes from a phase 3 randomized trial of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria who received prior eculizumab

Kulasekararaj

Hill

Langemeijer

et al. 2021

European J of Haematology

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Ravulizumab every 8 weeks showed non‐inferiority to eculizumab every 2 weeks in a 26‐week, phase 3, randomized controlled trial in adults with paroxysmal nocturnal hemoglobinuria (PNH) who were clinically stable on eculizumab (NCT03056040). We report results from the first 26 weeks of the extension period in which patients continued ravulizumab (n = 96) or switched from eculizumab to ravulizumab (n = 95). At week 52, mean (SD) lactate dehydrogenase levels increased 8.8% (29%) with ravulizumab‐ravulizumab and 5.8% (27%) with eculizumab‐ravulizumab from primary evaluation period baseline. During the extension period, four patients (ravulizumab‐ravulizumab, n = 3; eculizumab‐ravulizumab, n = 1) experienced breakthrough hemolysis, but none associated with serum free C5 ≥ 0.5 μg/mL. Mean Functional Assessment of Chronic Illness Therapy (FACIT)‐Fatigue scores remained stable through week 52. During the extension period, proportions of patients avoiding transfusion remained stable (ravulizumab‐ravulizumab, 86.5%; eculizumab‐ravulizumab, 83.2%); 81.2% and 81.1%, respectively, had stabilized hemoglobin. All patients maintained serum free C5 levels < 0.5 μg/mL. Adverse events were generally similar between groups, and rates were lower in the extension period. Adults with PNH on stable eculizumab therapy who received ravulizumab over 52 weeks experienced durable efficacy, with consistent efficacy in patients who received eculizumab during the primary evaluation period and then switched to ravulizumab. Ravulizumab was well tolerated.

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Section: Discussionmentioning

confidence: 99%

One‐year outcomes from a phase 3 randomized trial of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria who received prior eculizumab

Kulasekararaj

Hill

Langemeijer

et al. 2021

European J of Haematology

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“…Patients with PNH experience severe fatigue and reduced QoL, 19 which may be exacerbated in those who have other symptoms of PNH or a history of thromboembolism. 20 Improvements in fatigue and QoL seen during the primary evaluation period 13 were generally maintained throughout the extension period.…”

Section: Discussionmentioning

confidence: 99%

One-year efficacy and safety of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria naïve to complement inhibitor therapy: open-label extension of a randomized study

Schrezenmeier

Kulasekararaj

Mitchell

et al. 2020

Therapeutic Advances in Hematology

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Background: Ravulizumab, the only long-acting complement C5 inhibitor for adults with paroxysmal nocturnal hemoglobinuria (PNH), demonstrated non-inferiority to eculizumab after 26 weeks of treatment in complement inhibitor-naïve patients during a phase III randomized controlled trial. We present open-label extension results with up to 52 weeks of treatment. Methods: Patients assigned to ravulizumab every 8 weeks (q8w) or eculizumab every 2 weeks during the randomized primary evaluation period received ravulizumab q8w during the 26-week extension. Efficacy endpoints were lactate dehydrogenase (LDH) normalization, transfusion avoidance, breakthrough hemolysis (BTH), LDH levels, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale, and stabilized hemoglobin. Serum free C5 levels and safety were assessed. Outcomes as of the data cut-off (4 September 2018) were summarized using descriptive statistics. Results: Overall, 124 patients continued ravulizumab, and 119 switched from eculizumab to ravulizumab. During the extension, 43.5% and 40.3% of patients in the ravulizumab–ravulizumab and eculizumab–ravulizumab arms, respectively, achieved LDH normalization; 76.6% and 67.2% avoided transfusion. BTH decreased in the eculizumab–ravulizumab arm; no events were associated with free C5 ⩾0.5 μg/mL while receiving ravulizumab. Overall, 73.4% and 65.5% of patients in the ravulizumab–ravulizumab and eculizumab–ravulizumab arms, respectively, achieved stabilized hemoglobin. Similar proportions of patients achieved ⩾3-point improvement in FACIT-Fatigue at week 52 (ravulizumab–ravulizumab, 64.5%; eculizumab–ravulizumab, 57.1%). All patients maintained free C5 <0.5 μg/mL during the ravulizumab extension, including those who experienced C5 excursions ⩾0.5 μg/mL while receiving eculizumab during the primary evaluation period. Adverse events were comparable between groups and decreased over time. Conclusion: In adult, complement inhibitor–naïve patients with PNH, ravulizumab q8w for up to 52 weeks demonstrated durable efficacy and was well tolerated, with complete and sustained free C5 inhibition and a decreased incidence of BTH with no events associated with loss of free C5 control. Trial registration: ClinicalTrials.gov identifier, NCT02946463

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“…However, this does not fully explain why none of the patients actually followed the alert to contact the medical team. In particular for the most common reported symptom "fatigue", the patients may have shown signs of resignation as they had already previously learned of the sometimes limited therapeutic options (13). Second, fatigue is a highly complex symptom, which is di cult to assess by a simple question and thus may have triggered potentially false alarms.…”

Section: Discussionmentioning

confidence: 99%

“…Based on this extensive experience of ePRO systems in cancer, aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) patients are ideal candidates for such ePRO interventions. AA and PNH are rare chronic conditions, characterized by symptoms of bone marrow failure such as fatigue, bleeding and infections (11)(12)(13) in AA and by complications of hemolysis and thrombosis in PNH (14,15). Despite major improvements in therapies in the past decades, AA and PNH patients often remain symptomatic with signi cantly reduced HR-QoL as well as requiring longterm followup due to their risk for disease relapse, severe complications and late effects (16)(17)(18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

Feasibility of electronic patient-reported outcome monitoring with self-management advice and warning system in aplastic anemia and paroxysmal nocturnal hemoglobinuria – a pilot study (ePRO-AA-PNH)

Baenziger

Weisshaar

Arokoski³

et al. 2021

Preprint

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Introduction: Electronic patient-reported outcome (ePRO) systems have demonstrated to improve patient outcome in cancer, but have not yet been evaluated in patients with aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH). This pilot study evaluated the feasibility of an ePRO monitoring, self-management advice and warning system customized for AA and PNH patients.Methods: After adapting an ePRO system to the needs of AA and PNH patients (ePRO-AA-PNH), the application was tested by patients and their medical team for 6 months. Based on a predefined algorithm symptom reporting triggered self-management advice and prompts to contact clinicians in case of severe symptoms. Meanwhile the medical team could monitor ePROs in real-time and receive alerts of severe symptoms electronically. Results: Nine patients completed the study, showing a high adherence rate to the weekly symptom-reporting (72%), which decreased from 91 % to 53 % over the study period. Satisfaction was high: ePRO-AA-PNH was found easy to use, to understand and to integrate into daily life. Most patients (78%) would continue and all would recommend the application to other AA/PNH patients. Technical performance was rarely a barrier and healthcare providers saw ePRO-AA-PNH as a useful supplement, but missed the integration to clinical workflows and the hospital electronic health records (EHR). Conclusion: An ePRO system customized for AA and PNH was feasible to patients and their medical team in terms of adherence, satisfaction and performance, showing a high potential for these rare and chronic conditions. However, the integration into clinical workflows and hospital EHR is crucial for routine use.Trial registration: ClinicalTrials.gov identifier: NCT04128943, October 16 2019, https://clinicaltrials.gov/ct2/show/NCT04128943

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Fatigue, symptom burden, and health‐related quality of life in patients with myelodysplastic syndrome, aplastic anemia, and paroxysmal nocturnal hemoglobinuria

Cited by 42 publications

References 28 publications

One‐year outcomes from a phase 3 randomized trial of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria who received prior eculizumab

One‐year outcomes from a phase 3 randomized trial of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria who received prior eculizumab

One-year efficacy and safety of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria naïve to complement inhibitor therapy: open-label extension of a randomized study

Feasibility of electronic patient-reported outcome monitoring with self-management advice and warning system in aplastic anemia and paroxysmal nocturnal hemoglobinuria – a pilot study (ePRO-AA-PNH)

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