Use of disease-modifying therapies on the rise in SCD: US study
Chronic blood transfusion therapy use remained low over 8-year period
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The use of pharmaceutical disease-modifying therapies (pDMTs) has increased in recent years among both children and adults with sickle cell disease (SCD), according to a study analyzing U.S. claims data.
Over the same eight-year period, the use of chronic blood transfusion therapy (CBT) has remained low and has been concentrated mainly among those with the most severe SCD-related complications.
“These findings suggest treatment intensification in routine practice follows accumulating [complications] rather than preceding it,” researchers wrote. “Expanding CBT capacity and improving pDMT uptake may narrow gaps and better align real-world care.”
The study, “Real-world use of pharmacologic therapy and chronic blood transfusion in sickle cell disease, 2014–2021,” was published in the Annals of Hematology.
Stem cell transplant, gene therapy constrained by several factors
In SCD, inherited gene mutations cause normally oval-shaped red blood cells to assume a sickle-like shape. These sickled cells die much more quickly than healthy red blood cells, reducing oxygen delivery throughout the body. These abnormal cells are also more prone to form clumps, potentially blocking blood vessels and leading to painful episodes called vaso-occlusive crises (VOCs).
“Potentially curative options such as … stem cell transplantation and gene therapies remain constrained by donor availability, cost, and uncertain long-term durability, leaving most patients reliant on disease-modifying therapies (DMTs) to mitigate [disease] and improve survival,” the researchers wrote.
DMTs approved for SCD fall into two broad categories. The first comprises pDMTs, such as hydroxyurea, Endari (L-glutamine), and Adakveo (crizanlizumab-tmca), which are meant to reduce disease complications. The second comprises routine transfusion-based approaches, collectively known as chronic blood transfusion therapy (CBT).
However, “real-world patterns of CBT utilization, and how they compare with, or complement pDMT use, remain incompletely characterized” in SCD patients, “particularly among adults,” the researchers wrote.
Use of pDMTs increased steadily over the study period
With this in mind, a team of researchers in the U.S. set out to measure annual rates of CBT, pDMT, and combined therapy use in SCD patients, and to identify patient characteristics associated with each treatment pattern.
The team tapped into the Optum Labs Data Warehouse to analyze de-identified U.S. claims data spanning from 2014 to 2021. Of the 4,100 people with SCD selected for the study, about one-fifth were children.
Most patients (70%) had not received treatment, while 26% were on pDMTs alone, 3% received CBT alone, and 1% received both. CBT was defined as having at least six blood transfusions within one year.
Patients who received CBT alone or combined CBT and pDMT had higher rates of both acute and chronic SCD complications, as well as severe organ complications, including stroke, kidney disease, and chronic lung complications. Healthcare utilization was also generally higher in these two groups.
Over the study period, any pDMT use increased steadily, use of acute blood transfusion (less than six transfusions in a year) remained flat or declined, and CBT use rose only slightly, by 1%.
The steady rise in pDMT use was likely driven by the “gradual diffusion of newer agents in addition to the availability of hydroxyurea,” the researchers wrote.
Statistical analyses found that older age was significantly associated with lower use of both pDMT and CBT. Compared with pediatric patients, those aged 30 to 54 had 38% lower odds of being on pDMT alone, while those aged 55 and older had 64% lower odds. This age-specific pattern was more pronounced for CBT, with those same age groups having 56% and 80% lower odds of using those treatments, respectively.
Men with SCD accrue more [severe organ damage] … and undergo transfusion more frequently, and alongside higher cerebrovascular risk, these factors can prompt clinicians to escalate disease-modifying strategies.
For pDMTs, the inverse relationship with age may reflect differences in tolerability or perceived benefit, as well as competing treatment priorities in patients managing multiple conditions simultaneously, the team hypothesized.
Male sex was significantly associated with higher odds of pDMT-only use (by 30%) and combined pDMT and CBT use (by twofold) compared with female sex.
“A possible explanation is that men with SCD accrue more [severe organ damage] … and undergo transfusion more frequently, and alongside higher cerebrovascular risk, these factors can prompt clinicians to escalate disease-modifying strategies,” the team wrote.
A history of VOCs was significantly linked to higher odds of being in all three treatment groups, by two to three times. At the same time, severe organ complications were significantly associated with higher odds, by two to three times, of CBT-only use and combined therapy.
“In our national [group] of SCD patients that included pediatric and adult patients from 2014 to 2021, pDMT increased modestly while CBT use remained low and concentrated among patients with [more disease complications],” the team wrote. Still, “most patients were not on a DMT in a given year and older adults were least likely to receive disease-modifying care. Future work should target barriers to uptake and persistence across payers and regions and link utilization to patient-centered outcomes to identify who benefits and when to escalate therapy.”
