Hydroxyurea in Children with Sickle Cell Disease: Practice Patterns and Barriers to Utilization.

Abstract

Abstract 242Despite the Multicenter Study of Hydroxyurea (MSH) in sickle cell disease (SCD) documenting the efficacy of hydroxyurea (HU), it is underutilized in adults. Little is known about practice patterns of HU use in children with SCD and barriers to utilization. The objectives of this study were to: 1) evaluate practice patterns of HU utilization in children with SCD and 2) identify barriers to its use. We emailed a pilot-tested survey to members of the American Society of Pediatric Hematology/Oncology. The survey included provider demographics, characteristics of SCD population, criteria used to prescribe HU, and barriers to HU utilization. Descriptive statistics were performed and Spearman correlation used to evaluate factors associated with HU utilization. Thirty-one percent (n=350) of 1128 surveys were returned; 63% (220 of 350) care for children with SCD (97% physicians, 3% nurse practitioners). The median years in practice of these providers was 12 (IQR 5–20). Half of providers were female and 84% practiced in an urban teaching hospital. Half of providers have >100 SCD patients in their practice, with 43% stating SCD patients make up >20% of their practice. Most (87%) had heard of the NHLBI guidelines for SCD published in 2002, 78% had read these guidelines and 61% were aware of the HU Consensus Conference (NIH, 2008). Only 8% of providers have 50–90% of their SCD patients on HU, 54% have 10–30% of SCD patients on HU and 10% have fewer than 10% of SCD patients on HU. Most providers (90%) felt HU was effective or very effective for prevention of pain. Table 1 shows the most common criteria used to start HU. Over half of providers initiated HU therapy in patients aged <4 yrs. Twenty-six percent of providers reported more than 20% of their patients/families refused HU due to: fear of cancer (51%) and other side effects (62%), don't want to take medication (49%), required laboratory monitoring (28%), and don't think it will work (17%). Not all providers prescribed HU to eligible patients and their reasons are shown in Table 2. Provider utilization correlated with awareness of the NHLBI recommendations (r=0.4; p<0.0001) and the HU Consensus Conference (r=0.3; p<0.0001). Our survey suggests substantial variation in HU utilization in children with SCD. Many recommend HU for complications other than pain, despite insufficient evidence for its efficacy for these complications. The absence of a randomized trial of HU in children and the lack of formal guidelines may have led to HU use for indications not studied in the MSH trial. Many providers use frequent pain at home as criteria to start HU, reflecting emerging SCD pain literature and expansion of MSH criteria. Provider-related barriers to prescribing HU focus on reproductive issues (teratogenesis and infertility in males) despite low or insufficient evidence to support these concerns and patient compliance (with HU and the required laboratory monitoring). Common patient-related barriers included carcinogenesis, fear of side effects, and not wanting to take a medication. Barriers to HU use exist both on the part of providers and patients. Evaluating the potential unknown toxicities of HU that influence practice, exploring whether access to care contributes to potential noncompliance, and encouraging adherence research may decrease these barriers. In addition, studies to determine the effectiveness of HU for SCD complications other than pain are urgently needed as HU is currently used for a variety of complications for which this drug may or may not be effective.Table 1Criteria used by providers to start HUCriteriaProportion (%)Acute Chest Syndrome88≥3 painful episodes/year86Requiring hospitalization only42At home or requiring hospitalization44Chronic pain requiring frequent narcotic use70Priapism48Pulmonary Hypertension43Symptomatic Anemia40Stroke36Renal Failure15Ankle Ulcers12Low hemoglobin F levels9Elevated WBC count without evidence of infection6Table 2Provider-related barriers to HU useBarrierProportion (%)Patient compliance with taking medication86Patient compliance with blood tests85Lack of contraception in females85Patient's anticipation of side effects75Patient is too young68Concern for male infertility46Lack of formal guidelines for use in children30Provider discomfort with carcinogenic potential27Cost18Lack of time/resources to explain risks/benefits16Not FDA approved in children12Doubt effectiveness of HU11 Disclosures:No relevant conflicts of interest to declare.