Impact of acute pain on health care resource utilization and costs in sickle cell disease in the United States

Abstract Objective: Acute pain is common among patients with sickle cell disease (SCD), but there is limited knowledge of its economic burden. This study evaluated the impact of acute pain on health care resource utilization (HCRU) and direct medical costs among patients with SCD. Methods: The TriNetX Linked Network claims database and TriNetX Dataworks-USA electronic health record data were used to conduct a retrospective longitudinal cohort study in individuals aged ≥12 years who were diagnosed with SCD between October 1, 2015, and June 21, 2024. Acute pain was defined as an emergency department (ED) or inpatient encounter assigned an International Classification of Diseases, Tenth Revision, Clinical Modification code for generic pain or SCD crisis, during which intravenous pain medication was administered, or an opioid prescription was given within 7 days of the respective ED/inpatient encounter. The first observed encounter with pain occurring after at least 12 months of continuous health insurance coverage was defined as the index date. Patients with pain during the 12-month baseline period were excluded. Controls were patients with no evidence of pain during the study window and were assigned random pseudo-index dates after at least 12 months of prior continuous health insurance coverage. Patients were excluded if they had a diagnosis of sickle cell trait at any point during the study period or had evidence of gene therapy or stem cell transplantation prior to the index date. Patients were also required to have 12 months of continuous insurance coverage after the index. Analyses compared annual all-cause HCRU and direct medical costs (2023 US dollars) during the first 12 months post index between patients with SCD with and without acute pain. Comparisons were adjusted for demographic characteristics (including age at index, sex, race, ethnicity, geographic region, and type of insurance coverage), baseline clinical characteristics, SCD-related comorbidities (including chronic pulmonary disease, asthma, and hypertension), and SCD treatments (including hydroxyurea, L-glutamine, voxelotor, crizanlizumab-tmca, and erythropoietin-stimulating agents) using multivariable regression models. Results: The study population comprised 1, 966 patients with SCD, including those with (n=1, 082) and without (n=884) acute pain. Compared with patients without acute pain, patients with acute pain were younger (32 years vs 36 years; P. 001), more likely to be insured through Medicaid (73% vs 62%; P. 001), received more treatment with hydroxyurea (26% vs 13%; P. 001), and received more transfusions (25% vs 16%; P. 001) at baseline. Patients with acute pain were more likely to have higher baseline rates of comorbidities, most notably chronic pulmonary disease (27% vs 19%; P. 001) and asthma (23% vs 15%; P. 001). Patients with acute pain had a much greater probability of inpatient (odds ratio OR, 8. 53), outpatient (OR, 4. 56), and pharmacy (OR, 6. 96) HCRU compared with patients without acute pain (all P. 001). This resulted in a statistically significant regression-adjusted increase of 6, 108 in all-cause cost per patient per year, a 43% increase over patients without acute pain (20, 248 vs 14, 140, respectively). Limitation: In the study, acute pain was defined by the administration of intravenous pain medication or an opioid prescription. One limitation is that patients may still experience acute pain without receiving these medications and thus our sample may not include all patients with acute pain. Conclusions: Acute pain was associated with higher probability of 12-month HCRU and increased associated costs among patients with SCD, highlighting the considerable and previously underrecognized economic burden of acute pain in this population. These findings reinforce the necessity for new treatments to address the substantial unmet need in managing SCD-related acute pain.