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A downward trend in opioid prescribing practices for patients with sickle cell disease (SCD) followed the CDC's 2016 opioid guidelines for chronic pain, an analysis of claims data showed, but so did a steady increase in pain-related hospitalizations.

Compared with expected pre-guideline trends, the opioid dispensing rate, days of opioids supplied per prescription, and morphine-equivalent dosage all significantly declined from March 2016 to December 2019 among SCD patients (P<0.001 for all), reported researchers led by Hyeun Ah Kang, PhD, of the University of Texas at Austin.

Meanwhile, an upward trend in hospitalizations for vaso-occlusive crises (VOCs) accompanied those changes in prescribing, according to findings detailed in . In December 2019, about one in five SCD patients (19.6%) in the study had a VOC-related hospitalization, a full 7 percentage points higher compared with expected trends based on a scenario where the 2016 guidelines were never released (12.5%).

While the CDC's 2016 guideline was not intended to limit pain treatment for patients with SCD -- who often experience VOCs that may not be relieved by non-opioids -- the agency did not specifically exclude this group from its recommendations. The guidelines have been associated with decreased opioid use in the overall population and in patients with chronic pain.

"People with SCD are treated with excessive suspicion of faking pain and 'drug-seeking,' and are frequently undertreated for acute pain -- and there's good evidence that can increase the risk of hospitalization," said C. Patrick Carroll, MD, director of psychiatric services for the Johns Hopkins Sickle Cell Center for Adults in Baltimore, who was not involved in the study.

"That suspicion, along with lack of clinical expertise in an incredibly complex illness, render our patients vulnerable to swings in clinical culture around opioids, whether to undue optimism regarding chronic pain or excessive fear when treating acute pain," he told 乌鸦传媒. "The guidelines were a pivot-point and catalyst for clinical culture change, and it's plausible they interacted with the factors I mentioned to produce unintended consequences -- and we have seen some evidence that acute care rates have increased."

The study findings are particularly important, said Kang and co-authors, because reducing hospitalizations and emergency department visits are considered major treatment goals both by SCD patients and their physicians.

Federal guideline and policymakers "should carefully consider the negative outcomes that their interventions may present in vulnerable populations, as well as clearly communicate the intention and scope of the interventions," they wrote.

The CDC, referring to "lessons learned" from the development of the 2016 guideline, issued an updated guideline in 2022 that specifically excludes SCD -- as well as cancer-related pain, palliative care, and end-of-life care -- from its opioid recommendations for chronic pain. The updated guideline recommends that in the case of SCD, clinicians should refer to the on managing acute and chronic pain in SCD.

"While there are many aspects of the updated guidelines I applaud -- particularly a more careful approach to opioid failure and dose reductions in chronic pain -- what we owe people with SCD is a disease-specific evidence base for important clinical decision points, and developing multidisciplinary treatment centers that can guide implementation of good clinical care nationwide," Carroll said.

The study from Kang's group used health insurance claims data from the Merative MarketScan Commercial Database, ultimately including 14,979 patients with SCD (mean age 26 years) from January 2011 to December 2019. Individuals with SCD were included if they were 1 year of age or older, had no cancer diagnosis, and had pharmacy coverage for the month of measurement.

In January 2011, the opioid dispensing rate was 81.3 per 100 persons with SCD (81.3%). This rate declined during the pre-guideline period ending in February 2016 but accelerated after the March 2016 guideline. By December 2019, the dispensing rate for patients with SCD was 13 percentage points lower compared with a no-guideline scenario (57.6% vs 70.7%, respectively). Significant decreases were also seen in the number of days supplied and morphine milligram equivalents per prescription.

Monthly VOC-related hospitalization rates at the start of the study (23.1 per 100 patients) declined slightly up until the guidelines came out (0.10 per month), at which point the rate increased by 0.03 month until the end of the study.

In an exploratory subgroup analysis by age group, changes were seen to a greater degree among adult patients, but similar changes were seen in pediatric patients, notable since the guideline was intended to apply to patients 18 years and older with chronic pain.

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