Adherence to Iron Chelation Therapy and Associated Healthcare Resource Utilization and Costs in Medicaid Patients with Sickle Cell Disease
Authors: Vekeman Francis , Sasane Medha , Cheng Wendy Y , Ramanakumar Agnihotram V , Fortier Jonathan , Duh Mei S. , Paley Carole , Adams-Graves Patricia 
Published: October 2019

Abstract
Introduction: While adherence to iron chelation therapy (ICT) is critical for successful iron overload (IO) treatment among patients with sickle cell disease (SCD), published data indicate it is often suboptimal. Deferoxamine (DFO) and Deferasirox (DFX) are ICTs indicated for the treatment of chronic IO in patients with SCD. Lack of patient adherence may impact patient outcomes and increase cost of care. This study evaluated the economic burden of ICT non-adherence in patients with SCD from the state Medicaid program’s perspective.
Methods: Patients with SCD were identified from Florida, Iowa, Kansas, Mississippi, Missouri, and New Jersey (1997-2013) state Medicaid programs. Patients were required to have ≥1 ICD-9 diagnosis code for SCD (282.6), ≥1 prescription for DFO or DFX, and ≥6 months of continuous enrollment prior to the 1st DFO/DFX prescription (index date), which was defined as the baseline period. Adherence was estimated using the medication possession ratio (MPR), defined as the sum of the days of medication supply divided by the number of days between 1st and last prescription fill plus the days of supply of the last fill; a threshold of ≥0.80 was used to define optimal adherence. All-cause and SCD-specific resource utilization per-patient-per-month (PPPM) was assessed using cumulative rates, accounting for all visits observed, and compared between adherent and non-adherent patients using cumulative rate ratios (CRR). All-cause and SCD-specific healthcare costs were computed using mean cost PPPM. Regression models adjusting for baseline characteristics were used to assess resource utilization and cost differences between adherent and non-adherent patients.
Results: A total of 846 eligible patients with SCD were included with 77 in DFO-only, 686 in DFX-only), and 83 in DFO/DFX switch cohort. Mean (SD) MPR was 0.68 (0.27) for DFO-only patients and 0.75 (0.26) for DFX-only patients (p<0.05). Among all users of ICT, 409 (48.3%) were considered adherent. Adherent patients were slightly younger (19 vs. 21 years, p=0.003) than non-adherent patients. Rates of transfusions were comparable between the two groups (mean [SD] transfusions PPPM, adherent: 0.41 [0.47]; non-adherent: 0.40 [0.54], p=0.456) at baseline. The adjusted rate of all-cause IP visits PPPM was lower in adherent versus non-adherent patients (CRR=0.87 [95% CI: 0.83, 0.91]; p<0.001). The adjusted rates of all-cause outpatient (OP) visits (1.10 [1.08, 1.13], p<0.001) and ER visits (1.06 [1.01, 1.10], p=0.010) PPPM of adherent patients were higher in adherent patients than those in non-adherent patients. A similar trend was observed in SCD-specific resource utilization except for rates of ER visits, which were similar between cohorts. From cost perspective, total all-cause and SCD-specific costs were lower in adherent versus non-adherent patients primarily due to lower IP costs (Table 1). SCD-specific ER and OP costs were similar in both cohorts. All-cause pharmacy costs were higher in adherent versus non-adherent patients.
Conclusion: Published studies have reported low adherence to ICT, and a similar trend was found in this study. Adherent patients were observed to have less frequent hospitalizations and lower overall and SCD-specific IP costs compared to non-adherent patients. It should be noted that the rate of OP visits was higher in the adherent patients compared to non-adherent patients suggesting that adherent patients may be more closely monitored potentially resulting in better overall patient management and fewer hospitalizations. Additional analyses are needed to explore differences between adherent and non-adherent patients.
Table 1 Costs PPPM Adherent patients (N=409) [A] Non-adherent patients (N=437) [B] Adjusted cost difference[A] – [B] P -value All-cause, mean [SD] $4,766 [$4,388] $5,304 [$4,725] -$724 0.072 Inpatient $1,911 [$3,647] $2,996 [$4,439] -$947 0.016 Emergency room $27 [$87] $40 [$88] -$203 0.104 Outpatient $580 [$697] $485 [$617] $49 0.500 Pharmacy $2,248 [$1,949] $1,783 [$1,449] $432 0.004 Pharmacy without ICT $215 [$482] $274 [$544] -$50 0.192 SCD-specific, mean [SD] $2,237 [$3,679] $3,116 [$4,301] -$952 0.0160 Inpatient $1,776 [$3,546] $2,782 [$4,268] -$855 0.0160 Emergency room $18 [$63] $28 [$69] -$199 0.1200 Outpatient $443 [$658] $306 [$548] $105 0.1120

Disclosures
Vekeman: Novartis Pharmaceuticals: Research Funding. Sasane:Novartis Pharmaceuticals: Employment. Cheng:Novartis Pharmaceuticals: Research Funding. Ramanakumar:Novartis Pharmaceuticals: Research Funding. Fortier:Novartis Pharmaceuticals: Research Funding. Duh:Novartis Pharmaceuticals: Research Funding. Paley:Novartis Pharma: Employment. Adams-Graves:Novartis Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau.