Adherence, Clinical and Economic Outcomes in Patients with Sickle Cell Disease with Recurrent Vaso-Occlusive Crises Treated with L-Glutamine, Voxelotor, or Crizanlizumab Covered By Medicaid and Commercial Insurance in the United States

Introduction

Sickle cell disease (SCD) is a rare hemoglobinopathy characterized by sickled hemoglobin, which leads to vaso-occlusive crises (VOCs). Hydroxyurea and red blood cell transfusions (RBCTs), in addition to supportive care, have long been standard of care for patients with SCD with recurrent VOCs. Three chronic therapies, L-glutamine, voxelotor, and crizanlizumab, were recently approved by United States (US) regulators for the treatment of patients with SCD. Patients in the US are mainly covered by Medicaid and commercial insurance. This study descriptively compares real world adherence, VOC outcomes, and economic outcomes in patients with SCD with recurrent VOCs treated with either L-glutamine, voxelotor, or crizanlizumab covered by Medicaid and commercial insurance.

Methods

This retrospective analysis used the Merative™ MarketScan® Databases between January 1, 2015 and September 30, 2022, to identify patients with SCD, ≥2 VOCs/year during any 2 consecutive years, and ≥12 months continuous enrollment before and after the second VOC in the second consecutive year. Patients covered by Medicaid or commercial insurance with ≥1 claim for L-glutamine, voxelotor, or crizanlizumab at any point were included; the first claim was the index date. Patients were required to have ≥12 months of continuous enrollment before the index date (baseline) and ≥ 12 months of continuous enrollment after and including the index date (follow-up). Demographics were assessed at index. Adherence (i.e., proportion of days covered [PDC]) for index therapies were measured during follow-up. Mean number of VOCs and total healthcare costs were summarized descriptively during baseline and follow-up for those covered by Medicaid and commercial insurance. Measured VOCs include only those leading to a healthcare visit given this is captured from a claims database. Total healthcare costs were analyzed for patients with Medicaid fee-for-service (FFS) plans and commercial insurance.

Results

A total of 363 patients with Medicaid (L-glutamine: 217; voxelotor: 86; crizanlizumab: 60) and 77 patients with commercial insurance (L-glutamine: 37; voxelotor: 24; crizanlizumab: 16) initiated a recently approved chronic therapy and met inclusion criteria. Of the 363 patients with Medicaid, 223 were covered by FFS Medicaid. Mean (standard deviation [SD]) age was 22.2 (10.6) years and 29.2 (13.5) years for patients covered by Medicaid and commercial insurance, respectively. Most patients were female (Medicaid: 54.5%; Commercial: 61.0%).

Mean [SD] PDC was below 0.50 for both patients covered by Medicaid and commercial insurance (Medicaid: 0.36 [SD:0.28] and commercial: 0.43 [SD: 0.31]) and was lower for those covered by Medicaid. For both patients covered by Medicaid and commercial insurance, mean [SD] number of VOCs were similar in the follow-up and baseline periods (Medicaid: follow-up: 7.55 [8.93] vs baseline: 7.55 [SD: 8.38]); commercial: follow-up: 5.95 [13.37] vs baseline: 5.58 [10.56]).

The mean total healthcare costs were higher during follow-up compared to baseline for both patients covered by FFS Medicaid and commercial insurance, and the difference in costs was numerically higher for patients covered by commercial insurance (FFS Medicaid: +$42,547 vs. commercial: +$89,656). Most of the increase in the healthcare costs in the follow-up period was directly due to the recently approved chronic therapy costs for both patients covered by FFS Medicaid (67.2%; +$28,579) and commercial insurance (69.2%; +$62,019).

Conclusion

Although not all recently approved chronic therapies are indicated for VOC reduction, both patients covered by Medicaid and commercial insurance that received these therapies continued to experience frequent VOCs that require healthcare visits and had higher healthcare costs mostly due to these therapies. These results highlight the need for improved treatment options for patients with SCD with recurrent VOCs, as well as strategies to improve adherence to existing therapies.

Udeze:Vertex Pharmaceuticals Incorporated: Current Employment, Current equity holder in publicly-traded company. Jerry:Vertex Pharmaceuticals Incorporated: Other: Funded this work. Evans:Merative: Current Employment. Li:Vertex Pharmaceuticals Incorporated: Current Employment, Current equity holder in publicly-traded company. Jain:Vertex Pharmaceuticals Incorporated: Current Employment, Current equity holder in publicly-traded company. Andemariam:Connecticut Department of Public Health: Research Funding; Fulcrum Therapeutics: Other: Data Safety Monitoring Board / Adjudication Committee; Sanofi Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Health Resources and Services Administration: Research Funding; Vertex: Consultancy, Membership on an entity's Board of Directors or advisory committees; bluebird bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Editas: Other: Data Safety Monitoring Board / Adjudication Committee; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Hemanext: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; American Society of Hematology: Research Funding; Afimmune: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Accordant: Consultancy, Membership on an entity's Board of Directors or advisory committees.