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INTRODUCTION The C5 inhibitor eculizumab is the current standard of care for the treatment of PNH. However, some pts receiving eculizumab to treat PNH continue to experience ongoing hemolysis and anemia, resulting in red blood cell transfusion dependence, substantial unmet clinical needs, and considerable health economic burden. This study evaluated the treatment patterns of pts with PNH receiving eculizumab and compared HRU among blood transfusion-dependent (TD) pts versus blood transfusion-free (TF) pts in real-world clinical practice in the United States. METHODS Pts aged ≥12 years with ≥2 claims for eculizumab infusion between April 1, 2014, and September 30, 2019, were identified from the IBM® MarketScan® Research Databases. The index date was the first observed claim for eculizumab infusion with ≥3 months of continuous eligibility prior (baseline period). Pts with ≥1 diagnosis of indications other than PNH for eculizumab (ie, atypical hemolytic uremic syndrome, generalized myasthenia gravis, neuromyelitis optica spectrum disorder) during the baseline period or on the index date were excluded to identify pts with PNH. The full cohort of PNH pts treated with eculizumab were then stratified into the TD cohort (≥1 claim for blood transfusion within 6 months following any eculizumab infusion) or TF cohort. Patient demographic and clinical characteristics in the baseline period were compared between TD and TF cohorts using standardized differences (std diff), with >20% indicating substantial differences. Treatment patterns and HRU (all-cause and PNH-related) were evaluated during the observation period (ie, from index date to earliest date between end of continuous healthcare plan enrollment and end of data availability). Time from index date to treatment discontinuation among pts in the full cohort was assessed using Kaplan-Meier analysis. HRU was compared between TD and TF cohorts using incidence rate ratios (IRRs) adjusted for baseline covariates. RESULTS A total of 151 eculizumab users with PNH were identified as the full cohort; 55 (36%) were TD and 96 (64%) were TF. Mean (range) age was 36.7 (12-74) years among all pts (TD: 35.1 years; TF: 37.6 years). Overall, 56% of pts were female, with a higher proportion in the TD vs TF cohort (67% vs 49%; std diff = 38%). More pts in the TD vs TF cohort had blood transfusions (71% vs 18%; std diff = 127%) and use of corticosteroid therapy (46% vs 32%; std diff = 27%) during baseline. Baseline coagulopathy and aplastic anemia were more common in the TD vs TF cohort (coagulopathy: 49% vs 30%; std diff = 39%; aplastic anemia: 64% vs 43%; std diff = 43%). Myelodysplastic syndrome was present in 10% of the full cohort (TD: 13%; TF: 8%; std diff = 14%). During a mean observation period of 19 months for the overall sample (TD: 20 months; TF: 19 months), pts had a median (interquartile range) of 8 (3-30) eculizumab infusions (TD: 5 infusions; TF: 8 infusions) during maintenance phase; 29% of pts (TD: 21%; TF: 33%) had on average 14 days between maintenance eculizumab infusions; 61% of pts (TD: 66%; TF: 58%) discontinued eculizumab treatment (ie, gap of >42 days between 2 infusions) and the median time to treatment discontinuation was 254 days (TD: 180 days; TF: 337 days). Mean (range) number of blood transfusions among TD pts was 8.5 (1-54). During the observation period, pts in the TD cohort had 2.95 times more all-cause hospitalizations and 4.58 times more hospitalization days compared to pts in the TF cohort (all P < 0.05). Similar trends were observed for PNH-related hospitalizations. Results for all-cause and PNH-related HRU are presented in the Table. CONCLUSIONS This study demonstrated a considerable economic burden among pts with PNH treated with eculizumab, particularly among pts dependent on blood transfusions. TD eculizumab users comprised >36% of the overall sample, indicating that disease activity may not be well controlled. These pts had >4 times the number of hospitalization days compared to TF pts, emphasizing the substantial unmet clinical need despite treatment with eculizumab. These findings suggest that the current PNH standard of care may be insufficient for TD pts. Based on time between dosing intervals, >70% of PNH pts in this study were not dosed per label, and two-thirds of pts discontinued eculizumab within an average of a 1.5-year timeframe. New therapies are needed to reduce the considerable burden of pts with PNH. Disclosures Cheng: Apellis: Research Funding. Sarda:Apellis: Current Employment, Current equity holder in publicly-traded company. Mody-Patel:Apellis: Current Employment, Current equity holder in publicly-traded company. Krishnan:Apellis: Current Employment, Current equity holder in publicly-traded company. Yenikomshian:Apellis: Research Funding. Scoble:Apellis: Current Employment, Current equity holder in publicly-traded company. Mahendran:Apellis: Research Funding. Lejeune:Apellis: Research Funding. Yu:Apellis: Research Funding. Duh:Apellis: Research Funding; Takeda Oncology: Research Funding; GlaxoSmithKline: Research Funding; AstraZeneca: Research Funding; Blueprint Medicine: Research Funding; Novartis: Research Funding; Shire: Research Funding; Merck: Research Funding; Pharmacyclics: Research Funding.

INTRODUCTION Current pharmacologic management of patients who are diagnosed with paroxysmal nocturnal hemoglobinuria (PNH) includes C5 complement inhibitors, such as eculizumab. The standard dosage of eculizumab, administered via intravenous infusion, is 600 mg/week for the first 4 weeks (induction phase), 900 mg for the fifth dose 1 week later, and 900 mg biweekly thereafter (maintenance phase). There is limited information describing dosing patterns of eculizumab in clinical practice. The purpose of this study was to conduct a comprehensive assessment of the real-world dosing patterns of patients with PNH treated with eculizumab in a large US population. METHODS A retrospective longitudinal cohort study using provider-based claims data from the Symphony Health Integrated Dataverse® was conducted. Patients were ≥12 years of age and received ≥2 infusions of eculizumab between October 1, 2014, and September 30, 2019. The index date was defined as the first medical claim for eculizumab infusion with ≥3 months of prior continuous clinical activity, defined as ≥1 claim of any type per quarter (ie, the baseline period). Patients with ≥1 diagnosis of another indication for eculizumab, including atypical hemolytic uremic syndrome, generalized myasthenia gravis, and neuromyelitis optica spectrum disorder, during the baseline period or on the index date were excluded to identify patients with PNH. Patient baseline demographic and clinical characteristics, including PNH-related comorbidities and PNH-symptoms, were described. Mean starting dose and the proportion with high (>600 mg), label-recommended (600 mg), and low ( RESULTS A total of 707 patients with PNH who had ≥2 infusions of eculizumab during the study period were included in this analysis; mean observation period was 23.9 months. Mean age was 45.4 years, 55.7% were female, and 35.9% were from the South. The majority of patients (77.1%) were insured through a commercial insurance plan. Respectively, 32.5% and 6.8% of patients had a diagnosis for aplastic anemia and myelodysplastic syndrome during baseline. The most frequent comorbidities in this sample included hypertension (26.6%), coagulopathy (26.6%), and renal failure (20.5%). In addition, 85.1% of patients experienced anemia (other than aplastic anemia) at baseline. The mean (standard deviation) starting dose during the induction phase was 862 (412) mg; the proportion of patients with high, label-recommended, and low starting dose was 64.1%, 30.6%, and 5.4%, respectively. The mean (standard deviation) and mode dose was 859 (391) mg and 900 mg during the induction phase, and 1011 (333) mg and 900 mg during the maintenance phase. Respectively, 67.9%, 25.9%, and 6.2% of patients had a high, label-recommended, and low mean dose during the induction phase, and 45.9%, 41.6%, and 12.5% had a high, label-recommended, and low mean dose during the maintenance phase. CONCLUSIONS This study demonstrates that the majority of patients with PNH treated with eculizumab were started on a dose in the induction phase that was higher than the label-recommended dose of 600 mg, and the mean dose received during the maintenance phase was higher than the label-recommended dose of 900 mg in approximately half of all patients. Future analyses that investigate budget impact of eculizumab in patients with PNH should account for real-world dosing patterns in order to comprehensively assess costs and benefits. Disclosures Cheng: Apellis: Research Funding. Sarda:Apellis: Current Employment, Current equity holder in publicly-traded company. Mody-Patel:Apellis: Current Employment, Current equity holder in publicly-traded company. Krishnan:Apellis: Current Employment, Current equity holder in publicly-traded company. Yenikomshian:Apellis: Research Funding. Scoble:Apellis: Current Employment, Current equity holder in publicly-traded company. Kunzweiler:Apellis: Research Funding. Vu:Apellis: Research Funding. Cheung:Apellis: Research Funding. Duh:Merck: Research Funding; Pharmacyclics: Research Funding; Takeda Oncology: Research Funding; GlaxoSmithKline: Research Funding; AstraZeneca: Research Funding; Blueprint Medicine: Research Funding; Novartis: Research Funding; Shire: Research Funding; Apellis: Research Funding.