The recommendation from the 2014 National Heart, Lung, and Blood Institute guidelines1 to treat all adults with sickle cell anemia (SCA) and 3 or more moderate to severe pain crises within 1 year with hydroxyurea was rated as strong based on high-quality evidence reviewed in 2008.2,3 Despite benefits in reducing pain crises, hospitalizations, blood transfusions, and possibly mortality, it is thought that hydroxyurea is underused, although the extent of its use is unknown.2 We sought to document the use of hydroxyurea when indicated for SCA in a large insurance claims database.
Data were obtained from the deidentified Optum Normative Health Informatics database, a nationwide sample of commercial health and pharmacy claims from more than 36 million residents in all 50 states and Washington, DC.4,5 Compared with the US population, the database has more patients aged 18 to 54 years, 1.3% fewer women, 2.3% fewer blacks, 6.4% fewer Latinos, and 6.8% more whites.
Adults (aged ≥18 years) with 1 or more inpatient or outpatient claims between January 1, 2009, and June 30, 2013, for probable SCA were identified using International Classification of Diseases, Ninth Revision (ICD-9) codes 282.61 (HbSS disease without crisis) or 282.62 (HbSS disease with crisis) on at least 2 encounters. Patients were selected when they had 3 or more hospitalizations, emergency department (ED) visits, or both within 12 months that included 1 of the 5 most frequent diagnosis codes used for patients with SCA and pain crises (HbSS disease with crisis [282.62]; acute chest syndrome [517.3]; pain in limb [729.5]; chest pain, unspecified [786.50]; other chest pain [786.59]), independent of existing or continuing treatment with hydroxyurea. Treatment was defined as filling 1 or more hydroxyurea prescriptions during the 3, 6, or 12 months of continued enrollment following the third episode.
The percentage of treated patients, 95% confidence intervals, and χ2 for trend were calculated using SAS version 9.3 (SAS Institute Inc). A 2-sided P value of <.05 was considered statistically significant. This analysis was exempted from review by the Western Institutional Review Board.
Of an enrolled population of 26 631 901, we identified 2086 adults with probable SCA (Table). Of these, 677 had at least 3 pain-related hospitalizations or ED visits within 12 months and 570 had at least 3 months of coverage after the third episode. Among them, 86 (15.1%; 95% CI, 12.3%-18.3%) were treated with hydroxyurea within 3 months of their third encounter. The percentage of treated patients increased slightly to 18.2% (95% CI, 15.0%-21.8%) at 6 months and to 22.7% (95% CI, 18.9%-27.0%) at 12 months (P = .002 for trend).
Despite evidence demonstrating the benefits of hydroxyurea in patients with SCA and frequent pain crises,2 this analysis suggests that more than 3 of 4 patients who might benefit were not treated with this safe and inexpensive drug. Several barriers to treatment have been identified, including fear of adverse events, lack of clinician training, and failure to engage in shared decision making.2 Our estimate reflects the combined effect of all barriers to treatment, regardless of source.
This analysis was limited by the use of ICD-9 codes to identify patients with SCA, an approach that can lead to missing potentially eligible patients. In addition, because some pain crises may be managed without hospitalizations or ED visits, some patients with 3 or more crises and suitable for hydroxyurea may not have been included. Furthermore, this definition does not take into account the broadened criteria described in new guidelines for the use of hydroxyurea, such as patients who have daily pain that affects their quality of life.1
Our data do not include the large uninsured or publicly insured population who may have more limited access to health care or awareness of treatment options. Therefore, these findings may not be representative of the entire US population with SCA and may be a conservative estimate of the hydroxyurea treatment gap. To address this gap, it may be necessary to enhance patient outreach and clinician training and develop health care quality measures aimed at increasing the use of hydroxyurea for all patients who would benefit.
Corresponding Author: Nicolas Stettler, MD, MSCE, The Lewin Group, 3130 Fairview Park Dr, Falls Church, VA 22042 (email@example.com).
Author Contributions: Mr Melin had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: All authors.
Acquisition, analysis, or interpretation of data: Melin, Adejoro, Walczak.
Drafting of the manuscript: Stettler, Melin.
Critical revision of the manuscript for important intellectual content: McKierman, Adejoro, Walczak.
Statistical analysis: Stettler, Melin, Adejoro, Walczak.
Administrative, technical, or material support: Melin, Walczak.
Study supervision: Walczak.
Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
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