Lehrhaupt, Kerri

INTRODUCTION Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, hematologic disease characterized by chronic complement-mediated hemolysis. Treatment with the C5 inhibitor eculizumab has resulted in a reduction in intravascular hemolysis (IVH) and improvements in morbidity and mortality. However, in a single-center cohort of patients with PNH receiving treatment with eculizumab, 72% remained anemic and 36% continued to require transfusions due to ongoing IVH and extravascular hemolysis (McKinley CE, et al.Blood. 2017;130(Suppl 1):3471; Risitano AM, et al.Front Immunol. 2019;10:1157). This study aims to describe the burden of illness in patients with PNH currently being treated with C5 inhibitors (eculizumab and ravulizumab). Overall, the study aims to understand the clinical and hematological outcomes associated with burden of illness in about 150 patients with PNH globally. In these preliminary analyses, the impact of PNH on hematologic and clinical measures is assessed from patients in the United States. METHODS A cross-sectional survey was administered to adult patients ≥18 years of age in the United States with a self-reported diagnosis of PNH, recruited through a patient advocacy group. Inclusion criteria to complete the secure online survey included current treatment with either eculizumab or ravulizumab, informed consent, and agreement to adverse event reporting. This study was initiated in July 2020 and is ongoing. Results presented herein are preliminary. Impact of PNH on hematologic and clinical measures will be assessed using the following variables: diagnosis levels; and any patient history of blood transfusions, thrombotic events, renal impairment, fatigue, and other PNH-associated symptoms as well as dosing frequency and treatment patterns. For these preliminary analyses, descriptive statistics will be reported for patients who have completed the survey. RESULTS As of August 6, 2020, 58 adult patients with a median age of 52 years (range, 21-88) completed the survey, among which 78% were female. Current medications included eculizumab (n = 20 [34.5%]) or ravulizumab (n = 38 [65.5%]), as well as concurrent anticoagulants (n = 9 [15.5%]) and/or anti-thrombotics (n = 2 [3%]). Most patients initiated treatment with eculizumab (n = 20 [100%]) or with ravulizumab (n = 34 [90%]) ≥3 months before. Median (interquartile range) last known hemoglobin level for patients on eculizumab and ravulizumab was 9.3 g/dL (8.0-11.1) and 10.1 g/dL (8.9-11.5), respectively. Overall, 45 (82%) patients reported hemoglobin values <12 g/dL (eculizumab: 90%; ravulizumab: 78%). Forty (69%) patients reported having ≥1 red blood cell transfusion at any point during their disease. Within the previous 12 months, 53% and 26% of eculizumab- and ravulizumab-treated patients, respectively, had ≥1 transfusion, and 12% and 17% were unsure. Among those patients who had ever received ≥1 transfusion, 6% and 13% had >4 transfusions in the previous 12 months for eculizumab and ravulizumab, respectively. Seventeen patients (29%) reported ≥1 thrombotic event at any point during their disease. Seven patients reported thrombotic events over the previous 12 months; six were receiving ravulizumab. The majority (77%) of patients reported fatigue. Fatigue was reported by nearly 95% of eculizumab-treated patients and 68% of ravulizumab-treated patients. CONCLUSIONS Preliminary results from this burden of illness survey demonstrate that a majority of patients with PNH report remaining anemic, despite treatment with C5 inhibitors eculizumab and ravulizumab for a period of ≥3 months. Disclosures Dingli: Sanofi-Genzyme:Consultancy;Karyopharm Therapeutics:Research Funding;Bristol Myers Squibb:Research Funding;Millenium:Consultancy;Alexion:Consultancy;Apellis:Consultancy;Rigel:Consultancy;Janssen:Consultancy.Matos:Kantar:Current Employment.Lehrhaupt:Kantar:Current Employment.Krishnan:Apellis:Current Employment, Current equity holder in publicly-traded company.Sarda:Apellis:Current Employment, Current equity holder in publicly-traded company.Baver:Apellis:Current Employment, Current equity holder in publicly-traded company.

INTRODUCTION Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, hematologic disease characterized by chronic complement-mediated hemolysis. Treatment with the C5 inhibitor eculizumab has resulted in a reduction in intravascular hemolysis and improvements in morbidity and mortality. Even with the clinical benefit in PNH, eculizumab entails twice-monthly intravenous infusions in a hospital setting in most countries, adversely impacting patients' work productivity (Mastellos DC, et al.Semin Hematol. 2018;55(3):167-175). Lost productivity associated with eculizumab ranged from $344,000 in Russia to $4.3 million in the United States, without caregivers (Levy AR, et al.Blood. 2019;134(Supplement_1):4803). Furthermore, patients in a real-world study treated with eculizumab for 1 year experienced continued impairment in overall quality-of-life relative-to-normative reference scores for the general adult population (Ueda Y, et al.Int J Hematol. 2018;107(6):656-665). This study aims to understand the clinical, humanistic, and economic outcomes associated with burden of illness in about 150 patients with PNH globally. In these preliminary analyses, productivity loss and quality of life (QoL) in patients with PNH currently being treated with C5 inhibitors (eculizumab and ravulizumab) are assessed in patients in the United States. METHODS This cross-sectional survey administered to adult patients in the United States, ≥18 years of age, with self-reported diagnosis of PNH, was initiated in July 2020 and is ongoing. Patients were recruited through a patient advocacy group. Inclusion criteria to complete the secure online survey include current treatment with either eculizumab or ravulizumab, and agreement to provide informed consent and adverse event reporting. To investigate the impact of PNH on employment and activity, the Work Productivity and Activity Impairment-General Health (WPAI-GH) questionnaire was used. QoL was assessed using Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). For the preliminary WPAI-GH analysis presented here, descriptive statistics are reported for patients who have completed the survey thus far. Analyses examining the impact of PNH on FACIT-Fatigue, EORTC QLQ-C30, and other clinical outcomes assessments among patients on anti-C5 therapy are ongoing. RESULTS A total of 58 adult patients completed the survey as of August 6, 2020. Patients' median age was 52 years (range, 21-88) and 78% of patients were female. Twenty patients (34%) were on eculizumab and 38 (66%) were on ravulizumab. Most patients (93%) had initiated treatment ≥3 months prior to enrollment. In total, 23 (40%) patients reported that they were gainfully employed. Overall, 52% of employed patients reported missing hours of work in the prior 7 days due to their health problems (67% eculizumab and 43% ravulizumab). About 77% of working patients reported that their illness affected their productivity at work (89% eculizumab and 69% ravulizumab) due to the same reason. Employed patients reported an average of 13% (standard deviation, 21%) absenteeism (ie, work time lost due to being absent for illness in the previous week; eculizumab, 22% ± 29%, ravulizumab, 7% ± 12%). Patients reported 26 ± 27% impairment while working over the past 7 days (ie, presenteeism; eculizumab, 39 ± 31%, ravulizumab, 18 ± 22%). Total work productivity impairment was on average 32 ± 31% (eculizumab, 46 ± 35%; ravulizumab, 23 ± 24%). Nearly all patients (n = 54 [93%]) reported at least some impairment in their usual activities regardless of employment (eculizumab, 100%; ravulizumab, 90%). On average, patients reported 38 ± 23% of impaired activity in the previous week (eculizumab, 43 ± 20%; ravulizumab, 36 ± 25%). CONCLUSIONS Preliminary results from this burden of illness survey evaluating humanistic and economic outcomes in patients with PNH demonstrated substantial loss of work-related productivity, greatly diminished ability to work, and limitations in patients' usual activities while being treated with the C5 inhibitors eculizumab and ravulizumab. Disclosures Dingli: Karyopharm Therapeutics:Research Funding;Alexion:Consultancy;Bristol Myers Squibb:Research Funding;Janssen:Consultancy;Rigel:Consultancy;Apellis:Consultancy;Sanofi-Genzyme:Consultancy;Millenium:Consultancy.Matos:Kantar:Current Employment.Lehrhaupt:Kantar:Current Employment.Krishnan:Apellis:Current Employment, Current equity holder in publicly-traded company.Baver:Apellis:Current Employment, Current equity holder in publicly-traded company.Sarda:Apellis:Current Employment, Current equity holder in publicly-traded company.