Real-World Healthcare Resource Utilization (HRU) and Costs of Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Receiving Eculizumab in a US Population

Abstract

Introduction: To evaluate the economic burden and treatment patterns of patients with paroxysmal nocturnal hemoglobinuria (PNH) treated with eculizumab, a C5 inhibitor, who were defined as blood transfusion-dependent (TD) versus blood transfusion-free (TF) in the US population.

Methods: Patients aged at least 12 years with at least two claims for eculizumab infusion (first claim was the index date) were identified from the IBM^® MarketScan^® Research Databases (April 1, 2014-September 30, 2019). The overall PNH eculizumab user cohort was stratified into the TD cohort (i.e., at least one claim for blood transfusion within 6 months following any eculizumab infusion, including on the infusion date) or the TF cohort (i.e., all non-TD patients). Treatment patterns, healthcare resource utilization (HRU), and costs were evaluated and compared during follow-up (i.e., index date to end of enrollment or data availability).

Results: Of 151 patients in the overall cohort (mean age 36.7 years; 55.6% female), 55 were TD (mean age 35.1 years; 67.3% female) and 96 were TF (mean age 37.6 years; 49.0% female). A total of 61% of patients (TD, 66%; TF, 58%) discontinued eculizumab, with TD patients having a shorter median time to discontinuation (TD, 0.5 years; TF, 0.9 years). TD patients had more all-cause hospitalizations than TF patients (p < 0.05). TD patients incurred higher all-cause direct medical costs (adjusted cost difference = $247,848) and medical-related absenteeism costs (adjusted cost difference = $4186) than TF patients (all p < 0.05), largely driven by hospitalizations. Similar trends were observed for PNH-related HRU and costs.

Conclusions: The economic burden of patients with PNH treated with eculizumab is greater among those dependent on blood transfusions.

Keywords: Absenteeism; Blood transfusion; Economic burden; Eculizumab; Healthcare resource utilization; Medical costs; Paroxysmal nocturnal hemoglobinuria; Retrospective study; Treatment patterns.

Fig. 1

Patient disposition for eculizumab cohort. ICD-10-CM International Classification of Diseases, 10th Revision, Clinical Modification; PNH paroxysmal nocturnal hemoglobinuria. ¹Eculizumab was identified using the HCPCS procedure code J1300. ²Other indications of eculizumab include atypical hemolytic uremic syndrome (ICD-9-CM, 283.11; ICD-10-CM, D59.3), generalized myasthenia gravis (ICD-9-CM, 358.0x; ICD-10-CM, G70.0x), and neuromyelitis optica spectrum disorder (ICD-9-CM, 341.0; ICD-10-CM, G36.0). ³Defined as patients with at least one medical claim for blood transfusion within 6 months after an eculizumab infusion, including on the infusion date

Fig. 2

Kaplan–Maier rates of discontinuation for eculizumab users stratified by blood transfusion dependence^1–6. TD transfusion-dependent, TF transfusion-free. ¹Observation period was defined as the period from the index date (i.e., date of first eculizumab infusion) to the earliest of end of continuous healthcare plan enrollment or end of data availability (September 30, 2019). ²The induction phase was defined as the first 4 weeks of eculizumab treatment (i.e., the 28-day starting period beginning on the index date). ³The maintenance phase was defined as the fifth week of eculizumab treatment and onwards. ⁴Assessed among patients with at least two eculizumab infusions during the entire follow-up period (overall), induction (N = 127) or maintenance phase (N = 137), respectively. ⁵Discontinuation was defined as a gap of more than 42 days between infusions or the last infusion and the end of follow-up (i.e., the earliest of end of continuous healthcare plan enrollment or end of data availability). ⁶Duration of treatment was calculated among the subset of patients discontinuing treatment

Fig. 3

Health resource utilization of transfusion-dependent patients compared to transfusion-free patients among eculizumab users. *p < 0.05. CI confidence interval, ER emergency room, HRU healthcare resource utilization, IRR incidence rate ratio, PNH paroxysmal nocturnal hemoglobinuria. ¹The rate was calculated as the frequency of HRU divided by the total person-years. ²Adjusted incidence rate ratios were estimated using multivariate Poisson models adjusting for baseline covariates. ³The 95% confidence intervals and p values were generated using non-parametric bootstrap procedures using 999 replications. ⁴Included visits with laboratory medical claims, or home services and hospice visits. ⁵A medical service claim was considered to be PNH-related if it is associated with an ICD-9-CM or ICD-10-CM diagnosis of PNH in any position. ⁶Any 95% CI with an upper bound exceeding 11.0 has been truncated in the figure for PNH-related HRU

Fig. 4

Healthcare costs of eculizumab users stratified by blood transfusion dependence status. *p < 0.05. CI confidence interval, ER emergency room, HRU healthcare resource utilization, OP outpatient, PNH paroxysmal nocturnal hemoglobinuria, PPPY per patient per year, TD transfusion-dependent, TF transfusion-free. ¹Costs are from the payer's perspective and are inflated to $US 2020 using the US Medical Care consumer price index from the Bureau of Labor Statistics from the US Department of Labor. ²Adjusted cost differences were estimated using multivariate generalized linear models with gamma distribution and log-link. Covariates included gender and aplastic anemia. ³The 95% confidence intervals and p values were generated using non-parametric bootstrap procedures using 999 replications. ⁴Hospitalization costs included all costs incurred in an inpatient setting, excluding inpatient blood transfusion costs. Outpatient costs included all costs incurred in an outpatient setting excluding outpatient blood transfusion costs, IV administration costs, and eculizumab infusion costs. ⁵Blood transfusion costs included all costs incurred during an inpatient or outpatient blood transfusion. ⁶Other visits included visits with laboratory medical claims, or home services and hospice visits. ⁷Evaluated among patients aged less than 65 years (N = 144)