Improving Pain Management in Patients With Sickle Cell Disease

Sickle cell disease (SCD) is associated with debilitating acute and chronic pain that can occur without warning, frequently sending people to the emergency department (ED) or acute-care centers. Opioids are often the backbone of pain management for these patients, and the opioid epidemic plaguing the United States has some health-care professionals concerned about the risks of opioid abuse among patients with SCD.

Two studies presented at the 2017 ASH Annual Meeting shed light on pain-management strategies used by people with SCD. The encouraging results of each study were tempered by persistent challenges for pediatric patients transitioning to adult care.

Opioid Use Is Not a “Crisis” in SCD Patients

In a review of real-world data from more than 10,000 people with SCD, opioid use remained stable over time, unlike the rates of overuse and abuse seen in the general population.1 “The use of opioids by patients with SCD has nothing to do with the opioid epidemic,” lead author Samir K. Ballas, MD, from Thomas Jefferson University in Philadelphia, told ASH Clinical News. “Unfortunately, there is a general conception that patients with SCD take a lot of opioids. In a way, they are innocent victims of the opioid epidemic.”

The researchers reviewed claims from patients (aged ≥9 months) with SCD who were covered by either Medicaid or commercial insurance. Participants in the study were required to have either one inpatient or two outpatient claims per year between 2009 and 2014, and the population was divided into cohorts according to year of diagnosis.

For each of the annual cohorts, there were between 2,619 and 3,285 patients in the commercial insurance group and between 4,807 and 7,007 in the Medicaid group. About half of each cohort were women, but patients covered by Medicaid appeared to be younger than those covered by commercial insurance (mean age = 27 years and 18 years, respectively [ranges not provided]).

The proportion of patients with SCD who were prescribed opioids remained stable each year across the study period, and consistently more Medicaid patients used an opioid (65%-70%), compared with patients covered by commercial insurance (54%-57%; p values not reported). Medicaid patients also had higher numbers of vaso-occlusive crises and days on which opioids were supplied:

  • average number of claims: 8.8-9.3 per year (Medicaid) and 6.1-6.5 per year (commercial)
  • average days supplied: 106.1-122.5 per year (Medicaid) and 93.4-102.1 per year (commercial; p values not provided)

Among both payers, opioid claims and days supplied were stable over time, Dr. Ballas noted, but opioid use increased markedly as pediatric patients aged into the adult health-care system. Between 23 and 64 percent of patients younger than 12 years were prescribed opioids during the study period, compared with between 57 and 87 percent of patients older than 18 years (p values not provided).

“Pediatric patients do well, but once they become adults, they have worse outcomes,” Dr. Ballas said, “and the reasons for this are multifactorial.” This pattern may reflect changes in compliance, adherence, and insurance coverage as patients age, as well as chronic or accumulated damage from SCD.

“Opioids are good analgesics, and the best medications available to treat sickle cell-related pain,” he concluded, “but we still need to monitor patients to make sure [they] are using the drugs appropriately – at least until we have something better.”

The study’s findings are limited by its retrospective design.

Lowering Emergency Department Reliance in Patients With Sickle Cell Disease

Thanks to initiatives to improve care for Wisconsinites living with SCD, fewer patients are visiting the ED to manage pain, according to a longitudinal analysis of ED use among patients with SCD. While children and young adults had lower-than-expected ED reliance (EDR), the researchers, led by Ashima Singh, PhD, MS, from the Medical College of Wisconsin in Milwaukee, noted that ED use among patients in the young-adult “transition” age group increased.2

In this study, investigators estimated EDR among 609 patients with SCD over a five-year period to examine the effect of several SCD-related initiatives in the state.

“EDR among the sickle cell population is an indicator of quality of care and access to outpatient settings,” the authors explained. “In the state of Wisconsin, more recent efforts to improve patient care include setting up a sickle cell clinic for adult patients, creating an electronic health records–based registry for children with SCD, and [expanding the] hydroxyurea indication to all children ≥1 year of age with sickle cell anemia.”

Patients included in the study were enrolled continuously in Medicaid and had at least one sickle cell pain–related ED visit. The researchers defined EDR for pain as the proportion of ED visits among all ambulatory visits (calculated by dividing the number of ED visits for pain by the number of all hospital visits). Excessive ED use was defined as an EDR ≥0.33.

Participants were categorized into four age groups:

  • children (0-18 years; n=248)
  • transition group (those who turned 19 years old during the 5-year study period; n=54)
  • young adults (19-30 years; n=170)
  • adults (31-45 years; n=137)

Results from a linear mixed model (adjusted for age group and hydroxyurea adherence) demonstrated that the overall EDR was 0.24 for the entire population – lower than the “excessive use” threshold.

According to the study’s findings, EDR for children was significantly lower than for adults >30 years old (0.18 vs. 0.23; p=0.009). However, patients in the transition-age groups and young-adult age groups relied more heavily on ED visits than children (0.33 for both vs. 0.18; p<0.001).

When the researchers examined temporal patterns in EDR among age groups over the study period, they found that EDR was continuously below the established threshold of 0.33, though it significantly increased from 0.17 in 2011 to 0.21 in 2015 (p<0.001).

However, the EDR in the transition-age group continued to increase over time, from 0.23 in 2011 to 0.37 in 2015 (p=0.001), suggesting that “further interventions focusing on the transition-age group are needed to improve care and ensure smooth transition from the pediatric to adult health-care systems,” the authors concluded.

The study was limited by its retrospective nature, and because it was conducted in a single state, the results may not be generalizable to the larger U.S. patient population.

Also, both studies were completed before the FDA approval of L-glutamine oral powder in July 2017 (the second FDA-approved treatment for SCD), the availability of which may alter patients’ incidence and management of painful episodes.

Dr. Ballas and authors report financial relationships with Novartis and Global Blood Therapeutics; Dr. Singh and authors report no financial conflicts.


  1. Ballas SK, Kanter J, Agodoa I, et al. Opioid utilization patterns in United States patients with sickle cell disease. Abstract #130. Presented at the 2017 American Society of Hematology Annual Meeting, December 9, 2017; Atlanta, GA.
  2. Singh A, Yan K, Brandow AM, Panepinto JA. Longitudinal trend in emergency department reliance for pain among sickle cell disease patients in Wisconsin. Abstract 901. Presented at the 2017 American Society of Hematology Annual Meeting, December 9, 2017; Atlanta, GA.