Escalating Doses Of Hydroxyurea In Very Young Children With Sickle Cell Anemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 978-978
Author(s):  
Shangli Lian ◽  
Jeremie H. Estepp ◽  
Matthew P. Smeltzer ◽  
Winfred C. Wang
Keyword(s):  
Young Children ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Dose Escalation ◽  
Fixed Dose ◽  
Early Therapy ◽  
Hematologic Response ◽  
Very Young Children ◽  
The Impact

Abstract Background In the HUSOFT and BABY HUG trials (Wang, et al., J. Pediat, 2001 and Lancet, 2011), very young children (6-24 and 9-18 months old at entry, respectively) with sickle cell anemia (SCA) initiated hydroxyurea (HU) at a fixed dose of 20 mg/kg/day, which improved hematologic parameters, provided substantial clinical benefits, and had an excellent safety profile. These results encouraged parental acceptance of HU treatment in very young children with SCA and in some parents promoted an expectation of early therapy. At our institution, select children as young as 6 months of age have initiated HU upon parental request. As in HUSOFT and BABY HUG, these children have begun at a dose of ∼20 mg/kg/day but then had dose escalation, based on hematologic parameters, toward a maximal tolerated dose (Ware, et al., Blood, 2010). Because the impact of dose escalation in this population is unknown, we have retrospectively reviewed our experience. Methods Children with homozygous sickle cell anemia (HbSS) who began HU therapy prior to 18 months of age between June 2010 and October 2012 were retrospectively identified following IRB approval. Demographic data, dosage information, and laboratory results pre-HU and at last clinical follow-up were analyzed. Descriptive data are presented below as means (±SD) unless otherwise noted. Statistical comparisons were performed with the Exact Wilcoxon Signed Rank test. Results Participants (n=6; female=3) were begun on HU because of recurrent dactylitis (n=2) or parental request (n=4). The mean initial dose of HU was 19.1 (±1.6) mg/kg/d, which subsequently was escalated to 25.4 (±4.4) mg/kg/d over an average of 14.8 (±10.5; range, 4.9-32.1) months. HU therapy was interrupted briefly in 2 participants for neutropenia and reticulocytopenia, respectively. Both incidents were felt related to viral suppression and both participants resumed HU at their previous dosage without further toxicities. Hematologic response is summarized in the following table along with hematologic response data reported in the HUSOFT and BABY HUG trials in subjects of comparable age. Discussion Six patients with HbSS who were begun on treatment at a mean age of 12 months had their dose of hydroxyurea escalated over an average follow-up period of 15 months. Hematologic responses included marked increases in Hb level, HbF, and MCV and a decrease in ARC, along with relatively stable neutrophil and platelet counts. When compared with subjects of approximately the same age in the BABY HUG and HUSOFT trials, all of whom were treated at doses of ≤20 mg/kg/d, our patients may have demonstrated more robust changes in their Hb, HbF, MCV and ARC levels, possibly related to their higher hydroxyurea dosing. The ongoing BABY HUG follow-up studies should provide complementary information for subjects who are ≥3 years of age, since they are having dose escalation toward maximum tolerated dose (MTD) and will be evaluated over an extended period of time. Overall, our current data suggest that increasing hydroxyurea dosage starting at a very early age is safe and hematologically efficacious and warrants further exploration with the goal of maximizing clinical benefit. Disclosures: Off Label Use: Hydroxurea therapy in children with sickle cell disease.

scholarly journals Clinical and Laboratory Benefits of Early Initiation of Hydroxyurea with Pharmacokinetic Guided Dosing for Young Children with Sickle Cell Anemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 507-507 ◽  
Author(s):  
Patrick T. McGann ◽  
Omar Niss ◽  
Min Dong ◽  
Anu Marahatta ◽  
Tomoyuki Mizuno ◽  
...  
Keyword(s):  
Young Children ◽  
Sickle Cell ◽  
Cystatin C ◽  
Sickle Cell Anemia ◽  
Research Funding ◽  
Laboratory Data ◽  
Advisory Board ◽  
Young Cohort

Abstract Background: Hydroxyurea is now the standard of care for children with sickle cell anemia (SCA). Results from the BABY HUG study and recommendations from the 2014 NHLBI Guidelines have led to early initiation (increasingly before 1 year of age) of hydroxyurea for many patients. Given the known variability in hydroxyurea pharmacokinetics (PK), treatment response (HbF%), and maximum tolerated dose (MTD), we hypothesized that individualized dosing would provide the optimal treatment approach. Methods: The Therapeutic Response Evaluation and Adherence Trial (TREAT, ClinicalTrials.gov NCT02286154) is a prospective study of a personalized, PK-guided dosing model of hydroxyurea for children with SCA. Using population PK model-based Bayesian estimation, each participant's PK data are used to generate an individualized starting hydroxyurea dose that targets an area under the curve associated with actual MTD. Clinical follow-up and subsequent dose adjustments target MTD, usually defined by ANC<3.0x109/L. We analyzed clinical and laboratory data for TREAT participants who started hydroxyurea before 2 years of age, to allow for comparison to published results from BABY HUG, which included a similar young cohort but with conservative weight-based dosing of 20 mg/kg/day. TREAT participants had ongoing clinical and research evaluations of organ function, including transcranial doppler (TCD) studies, RBC pit counts, and cystatin C measurements. Results:The analysis of children starting hydroxyurea before 2 years of age included 33 participants (of 47 total TREAT enrollments), who contributed a total of 59.5 patient-years of hydroxyurea therapy. The mean age (±SD) at hydroxyurea initiation was 1.0±0.4 years of age. The average PK-guided, individualized starting dose was 27.8±5.3 mg/kg/day, higher than conventional and BABY HUG initial dosing (20 mg/kg/day). For children who have completed 12 months of therapy (n=24), effects in hematologic laboratory data are remarkable with average 35.9±8.9% HbF and hemoglobin concentration of 10.2±1.1 g/dL after 12 months of therapy (compared to 29.3±8.8% and 9.2±1.3 g/dL at baseline). The majority (70%) of these participants have HbF>30% and almost half achieved HbF>40% after 12 months of hydroxyurea. This hematological response is more robust than what was observed in BABY HUG (HbF=22.4%, Hb=9.1 g/dL after two years of therapy, Wang WC et al. Lancet 2011). In the TREAT cohort, there were no episodes of dactylitis, acute splenic sequestration, or stroke. There were 111 emergency room or sick outpatient clinic visits for this young cohort; 107 ED/clinic visits (without subsequent hospitalization) were for fever, URI symptoms, GI illness, or other non-specific complaints unrelated to SCA, while only 4 (3.6%) visits were for pain. There were 38 hospitalizations in 17 participants, mostly for routine evaluation of fever (66%), but no positive blood cultures and no admissions for febrile neutropenia. The average length of hospitalization was 2.8±2.4 days with 81% of participants discharged within 72 hours of admission. There were 3 episodes of acute chest syndrome in 2 patients, two of whom required PRBC transfusion. Including all types of visits, there were only 6 pain events, equivalent to 10.1 pain events per 100 patient-years, which is much lower than the published 94 events per 100 patient-years in the hydroxyurea treatment arm of BABY HUG (Thornburg CD et al. Blood 2012). There were 37 TCD exams performed in 16 participants, all normal except for one patient with conditional velocities that normalized with hydroxyurea. There were no significant differences from baseline to month 12 in either RBC pit counts or cystatin C values. Conclusions: Hydroxyurea initiation at an early age using PK-guided dosing provides significant clinical benefits for young children with sickle cell anemia. These TREAT study data suggest that initiating hydroxyurea around one year of life using a personalized dosing strategy can provide better clinical and laboratory benefits than starting at the conventional 20 mg/kg/day weight-based dose. Very high HbF levels are observed at modest and well-tolerated doses of hydroxyurea, perhaps because treatment was initiated before the process of HbF inactivation is complete. Continued long-term follow-up of these patients will determine whether these will be sustained and able to prevent both short- and long-term complications of SCA. Disclosures Malik: CSL Behring: Patents & Royalties. Quinn:Silver Lake Research Corporation: Research Funding; Global Blood Therapeutics: Research Funding; Amgen: Research Funding. Ware:Biomedomics: Research Funding; Nova Laboratories: Consultancy; Bristol Myers Squibb: Research Funding; Addmedica: Research Funding; Global Blood Therapeutics: Other: advisory board; Agios: Other: advisory board; Novartis: Membership on an entity's Board of Directors or advisory committees.

Hydroxyurea Treatment of Young Children with Sickle Cell Anemia: Safety and Efficacy of Continued Treatment – the BABY HUG Follow-up Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 7-7 ◽  
Author(s):  
Zora R. Rogers ◽  
Billie Fish ◽  
Zhaoyu Luo ◽  
Rathi V. Iyer ◽  
Courtney D. Thornburg ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Hospital Admissions ◽  
Controlled Trial ◽  
Laboratory Data ◽  
Acute Chest Syndrome ◽  
Follow Up Study ◽  
Hydroxyurea Treatment ◽  
The Impact

Abstract Abstract 7 BABY HUG [Clinical Trials #NCT00006400], an NIH-NICHD sponsored randomized placebo-controlled trial showed that hydroxyurea (HU) administered to 9–18 month old children with sickle cell anemia (SCA) provides substantial clinical benefit. Benefits include a decrease in pain crises, acute chest syndrome events, need for transfusion and hospital admission; hematologic improvement include higher total and fetal hemoglobin concentration, larger red cell size, and lower WBC counts with toxicity limited to transient reduction in absolute neutrophil count (ANC) [Lancet 2011; 377:1663–72]. The parent or guardian of all 176 children who completed at least 18 months of randomized treatment were offered participation in an initial observational BABY HUG Follow-Up Study and 163 (93%) consented to participate. Clinical and laboratory data were collected every 6 months by structured abstraction of the medical record regarding use of clinically prescribed HU (dose escalation recommended), blood counts, clinical imaging, and sickle cell-related events. At the time of enrollment the family did not know their child's randomized study treatment assignment; 133 (82%) initially chose clinical prescription of open-label HU. Acceptance of HU has remained high through 36 months of follow-up; during each 6 month data collection period 68–75% of participants reported having taken HU. Only 2 patients have left the study (due to relocation) and more than 93% of expected data have been collected. Preliminary analyses as of May 2011, including 417 patient years (pt-yrs) of follow up, demonstrate that in comparison to participants not taking HU, children who continue to take HU have statistically lower rates of pain crises requiring emergency department (ED) visits, episodic transfusions, and hospital admissions for any reason, including acute chest syndrome or febrile illness (see table). The substantial decrease in acute chest syndrome episodes is similar to the effect demonstrated with HU use in the randomized BABY HUG trial in younger infants and consistent with published trials detailing the benefit of HU therapy in older children and adults. The decrease in the rate of admission for febrile events in HU-treated patients is also comparable to that in the randomized trial, but the reason for this benefit is uncertain. There was no difference in hospitalization rates for painful events including dactylitis. Two patients in the non-HU group had a stroke. There were no differences between groups in the frequency of a palpable spleen or rate of acute splenic sequestration crises. Through 36 months of follow up children taking HU had persistently higher hemoglobin and MCV, and lower WBC and ANC than those not taking HU. Results of these analyses including growth and development assessments will enhance our understanding of the impact of HU use in children with SCA starting at a very young age. The accruing data from the BABY HUG Follow-Up Study demonstrate a continuation of the substantial benefits of early HU therapy with no discernable additional toxicities. Ongoing follow up of this cohort is essential to fully define these benefits as children grow, and to observe for late toxicity.Event Rate per 100 pt-yrsHUNo HUp valueED visit for Pain Crisis28.853.60.004Episodic Transfusion18.334.00.010Hospital Admission (any cause)74.9133.20.001Acute Chest Syndrome (admission)9.522.30.0001Febrile Illness (admission)30.764.3<.001Pain Crisis (admission)18.630.40.102 Disclosures: Off Label Use: Hydroxyurea is not indicated for treatment of children with sickle cell disease. Use of this medication was for clinical indications and not mandated by this observational study.

scholarly journals Impact of TCD Screening Protocol on the Incidence of Hemorrhagic Stroke in Children and Young Adults with Sickle Cell Disease

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3402-3402 ◽  
Author(s):  
Julie Kanter ◽  
Janet Kwiatkowski ◽  
Heather J. Fullerton ◽  
Jenifer Voeks ◽  
Ellen Debenham ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Stroke Prevention ◽  
Hemorrhagic Stroke ◽  
Cell Disease ◽  
Increased Risk ◽  
The Mean ◽  
The Impact

Abstract Background: Primary hemorrhagic stroke is a rare complication of sickle cell disease (SCD) that usually occurs in adults. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) and Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP 2) established routine transcranial Doppler ultrasound (TCD) screening with indefinite chronic red cell transfusions (CRCT) for patients with abnormal TCD as standard of care. Despite a notable improvement in the incidence of infarctive stroke in children with SCD after the introduction of TCD screening protocols, it is unclear how this protocol will affect the rate of hemorrhagic stroke. Presumably, early TCD screening and subsequent initiation of CRCT in high risk patients will prevent the progression of cerebral vasculopathy, which should decrease the risk of hemorrhagic stroke; however this has not been proven. Using the large multicenter cohort of children who participated in STOP and/or STOP 2 trials, we sought to assess whether the rate of hemorrhagic stroke was impacted by the use of TCD screening and/or CRCT. Subjects and Methods: Between 1995 and 2005, STOP and STOP 2 (STOP/2) were conducted at 26 sites in the US and Canada. These studies included 3835 children, ages 2 to 16 y with SCD type SS or S-beta-0-thalassemia. Participation in STOP/2 required at least a single screening TCD for randomization. Patients on STOP 2 also had an observational arm for children started on CRCT who had an abnormal TCD. The Post-STOP study was designed to follow-up the outcomes of children who participated in one or both of trials. For all participants the date of their last encounter in STOP/2 was defined as the start of their Post-STOP period. 19 of the 26 original study sites participated in Post-STOP, contributing a total of 3539 (92%) of the STOP/2 subjects. After exit from STOP/2, these children received TCD screening and treatment according to local practices. Data abstractors visited each clinical site and obtained retrospective data from STOP/2 study exit to 2012-2014 including follow-up TCD and brain imaging results, clinical information, and laboratory results. Two separate neurologists, blinded to STOP/2 status and prior TCD and neuroimaging results adjudicated all suspected strokes. Results: Follow-up data were available for 2850 of the 3539 subjects (81%). Twelve children who had a stroke during the STOP study period were further excluded from this analysis resulting 2838 subjects. The mean age at the start of Post-STOP was 10.5 years and mean duration of follow-up after exiting STOP/2 until time of last medical encounter was 9.1 years. A total of 31 patients had a primary hemorrhagic stroke during the Post-STOP observation period (incidence 0.12 per 100 pt years). The mean age at time of stroke was 16.2+5.6 (median 15.3 range (4.8-30.2) years of age. Of those 31 patients, only 52% had a TCD during Post-STOP prior to the event. Seven of those children who underwent screening had documentation of an abnormal TCD prior to the event (5 during STOP era and/or 3 Post-STOP). However, only 1/7 patients (14%) were documented on CRCT at the time of the stroke (4 patients were receiving HU and 2 patients had unknown treatment). Discussion: Although less common than infarctive stroke, patients with SCD are at increased risk for hemorrhagic stroke. There is an increased risk of mortality for patients who suffer from hemorrhagic stroke (up to 26% in some reports in the 2 weeks after the event). It is unclear if TCD screening and subsequent initiation of CRCT will impact the rate of hemorrhagic stroke in the long term. In our results, a similar incidence of primary hemorrhagic stroke was noted although the patients were overall younger than previously reported (16.5+/- 5.5 years versus 20-29 years in Cooperative Study of Sickle Cell Disease). Many patients who had a hemorrhagic stroke (48%) had not undergone TCD screening during the Post-Stop period. Additionally, although a safe stopping point for CRCT has not been established in patients who have had an abnormal TCD, only 1 patient was documented on CRCT at the time of the event (14%). Thus, it is unclear at this time whether TCD screening and subsequent, lifelong continuation of CRCT could have prevented these other events. Clearly, these results demonstrate that improved implementation of STOP protocol is needed as well as further evaluation of the impact of this protocol on the incidence of hemorrhagic stroke. Disclosures No relevant conflicts of interest to declare.

scholarly journals Optimizing Hydroxyurea Dosing in Sickle Cell Anemia: The Uganda MTD Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 520-520 ◽  
Author(s):  
Chandy C. John ◽  
Robert Opoka ◽  
Teresa Latham ◽  
Heather Hume ◽  
Maria Nakafeero ◽  
...  
Keyword(s):  
Adverse Events ◽  
Board Of Directors ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Dose Escalation ◽  
Fixed Dose ◽  
Primary Study ◽  
Advisory Committees ◽  
Low Resource Settings ◽  
Low Resource

Introduction. Hydroxyurea treatment has proven safety, feasibility, and efficacy for children with sickle cell anemia living in sub-Saharan Africa. Even in malaria endemic regions, hydroxyurea is safe and has been shown to reduce vaso-occlusive events and lower mortality. The optimal dosing regimen is not known, however, and specifically whether a fixed dose at 15-20 mg/kg/day is better than escalation to maximum tolerated dose (MTD) at 25-30 mg/kg/day. Particularly in low-resource settings, additional drug-related toxicities and monitoring costs associated with dose escalation could outweigh potential laboratory and clinical benefits. Methods. Children with sickle cell anemia previously enrolled in NOHARM (NCT01976416) received hydroxyurea at ~20 mg/kg/day during the open-label portion of that trial, after which they transitioned to commercial supply at that same daily dose. All were then offered enrollment in the NOHARM MTD trial (NCT03128515), a double-blinded trial with 1:1 randomization between continuing fixed-dose oral hydroxyurea (20 ± 2.5 mg/kg/day) versus dose-escalation to MTD (30 ± 2.5 mg/kg/day), using hydroxyurea tablets donated by Addmedica. The primary study outcome was the proportion of study participants who achieved either hemoglobin ≥9.0 g/dL or fetal hemoglobin ≥20% after 24 months of treatment. Secondary outcomes included sickle-related clinical adverse events, malaria events, and laboratory toxicities. We now present the main results of the NOHARM MTD trial. Results. A total of 187 children enrolled and began study treatment: 94 children (4.8 ± 0.9 years, 55 males) received hydroxyurea at fixed dose versus 93 who received hydroxyurea with dose escalation (4.6 ± 1.0 years, 47 males). At Month 6 of study treatment the average doses were 19.3 ± 1.7 mg/kg/day and 29.0 ± 3.5 mg/kg/day, respectively, and these dose differences were continued through Month 12 and Month 18. The trial was terminated prematurely by the independent Data Safety Monitoring Board after 146 children had reached Month 18, when the clinical complications and interventions were significantly fewer among children randomized to MTD compared to fixed-dose. The incidence rate ratio (IRR) with 95% confidence intervals (CI) included the following: all sickle-related Adverse Events [IRR = 0.43, CI = (0.34, 0.56), P&lt;0.00001]; vaso-occlusive crises [IRR = 0.43, CI = (0.33, 0.56), P&lt;0.00001]; acute chest syndrome/pneumonia [IRR = 0.27, CI = (0.11, 0.55), P=0.001]; transfusions [IRR = 0.29, CI = (0.20, 0.43), P&lt;0.00001]; and hospitalizations [IRR = 0.21, CI = (0.13, 0.34), P&lt;0.00001]. The rates of Laboratory Adverse Events were similar between treatment arms [IRR = 0.83, CI = (0.60, 1.15), P=NS] and dose-limiting toxicities were equivalent [IRR = 1.01, CI = (0.66, 1.54), P=NS] without any episodes of severe neutropenia or thrombocytopenia. Superior laboratory benefits were observed in the dose-escalation arm, with higher hemoglobin (8.7 versus 8.3 g/dL, P=0.006) and fetal hemoglobin (30.5 versus 18.2%, P&lt;0.0001), and lower reticulocyte counts (157 versus 261 x 109/L, P&lt;0.0001) and neutrophil counts (3.4 versus 5.1 x 109/L, P&lt;0.0001). At the time of study closure, more children on the dose-escalation arm had achieved the primary study endpoint compared to those on fixed-dose hydroxyurea (86% versus 37%, P&lt;0.0001). Conclusion. NOHARM MTD is the first randomized controlled clinical trial to compare hydroxyurea at fixed-dose versus escalation to MTD in either high- or low-resource settings. Hydroxyurea escalated to MTD at ~30 mg/kg/day had superior clinical and laboratory efficacy compared to fixed-dose treatment at ~20 mg/kg/day in this high-risk population, without any increase in toxicity. Optimal hydroxyurea dosing to MTD at ~30 mg/kg/day is therefore recommended for children with sickle cell anemia living in sub-Saharan Africa, which represents an important paradigm shift from the concept of low-dose daily treatment. Increasing access to hydroxyurea at optimal doses will require concerted efforts that include training and implementation strategies, to enable safe and effective hydroxyurea dose escalation for children in low-resource settings. Disclosures Ware: Bristol Myers Squibb: Other: Research Drug Donation; Addmedica: Other: Research Drug Donation; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Nova Laboratories: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: DSMB.

scholarly journals Prediction of adverse outcomes in children with sickle cell anemia: a study of the Dallas Newborn Cohort

Blood ◽  
2008 ◽  
Vol 111 (2) ◽  
pp. 544-548 ◽  
Author(s):  
Charles T. Quinn ◽  
Nancy J. Lee ◽  
Elizabeth P. Shull ◽  
Naveed Ahmad ◽  
Zora R. Rogers ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Adverse Events ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Adverse Outcomes ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Clinical Predictors ◽  
Very Young Children

The Cooperative Study of Sickle Cell Disease reported that dactylitis, severe anemia, and leukocytosis in very young children with sickle cell disease (SCD) increased the risk of later adverse outcomes, including death, stroke, frequent pain, and recurrent acute chest syndrome. This model has not been validated in other cohorts. We evaluated its performance in the Dallas Newborn Cohort, a newborn inception cohort of children with SCD. We studied 168 children (55% male, 97% sickle cell anemia) with a mean follow-up of 7.1 years who provided 1188 patient-years of observation. Of the 23 (13.7%) subjects who experienced adverse events, 2 (1.2%) died, 14 (8.3%) had a stroke, 4 (2.4%) had frequent pain, and 3 (1.8%) had recurrent acute chest syndrome. No relationship existed between early clinical predictors and later adverse outcomes, with the possible exception of leukocyte count. Most subjects who experienced adverse events were predicted to be at low risk for those events. No subject who was predicted to be at high risk actually experienced an adverse outcome. The sensitivity of the model did not rise above 20% until specificity fell below 60%. We suggest that this model not be used as a criterion to initiate early interventions for SCD.

Costs Associated with the Care of Very Young Children with Sickle Cell Anemia (SCA): Analysis from the BABY HUG Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 171-171
Author(s):  
Winfred C. Wang ◽  
Suzette O. Oyeku ◽  
Zhaoyu Luo ◽  
Sheree L. Boulet ◽  
Scott T. Miller ◽  
...  
Keyword(s):  
Young Children ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Inpatient Cost ◽  
Acute Chest Syndrome ◽  
Costs Of Care ◽  
Very Young Children ◽  
Thomson Reuters ◽  
Hydroxyurea Treatment ◽  
Hydroxyurea Therapy

Abstract Abstract 171 Background: The BABY HUG trial was a multi-center double-blinded randomized comparison of hydroxyurea (HU) versus placebo in infants (mean age 13.6 mo. at entry) with HbSS/Sβ° thalassemia who were followed for 2 years [Lancet 377(2011):1663–1672; Clinical Trials #NCT00006400]. Hydroxyurea therapy was associated with less pain, dactylitis, acute chest syndrome (ACS), hospitalization (HSN), and transfusion (TX) and with improved hematologic values; toxicity was limited to mild-moderate neutropenia. On the basis of the safety and efficacy data from this trial, it was concluded that hydroxyurea therapy can be considered for all very young children with sickle cell anemia (SCA). With anticipated broader use of hydroxyurea in this population, we examined estimated medical costs of care (based on Medicaid reimbursement) in treated versus placebo subjects. Methods: The BABY HUG database (C-TASC, Baltimore, MD) was utilized to compare inpatient events in subjects receiving hydroxyurea with those receiving placebo. Unit costs were estimated from the 2009 Thomson Reuters MarketScan® Multi-state Medicaid Database for children with HbSS (ICD-9 codes 282.61 or 282.62), ages 1–3 years. Inpatient costs included emergency department (ED) costs for admissions from an ED in about 80% of the 748 admissions in the database. Inpatient cost estimates were based on length of stay (LOS) modified by a diagnosis of ACS or splenic sequestration (SpS) or a procedure code for a TX. Outpatient expenses were estimated based on the schedule required for BABY HUG (and recommended for clinical use) and a “standard” schedule for 1–3 year-olds with SCA based on management protocols at 3 pediatric sickle cell centers in the US. Results: 96 subjects were randomized to hydroxyurea (83 completed the trial); 97 received placebo (84 completed the trial). In the full study, there were 232 hospitalizations (for any cause) in those receiving hydroxyurea and 324 in those on placebo; inpatient data were captured for only the final 77% of admissions (between 2/06 and 9/09). The LOS for subjects receiving hydroxyurea (mean 3.7, median 3, range 1–9 days) did not differ from those receiving placebo (3.6, 3, 1–13). Estimated inpatient and outpatient costs are shown in Tables 1 and 2. When inpatient and outpatient expenses were combined, the annual cost for 1–3 year-old children with SCA was $11,345 on hydroxyurea and $14,815 on placebo, a difference of $3,470. Discussion/Conclusion: Despite increased outpatient care expenses from clinic visits, laboratory monitoring, and hydroxyurea, savings on inpatient care resulted in an overall reduction in estimated annual per patient expenditure of approximately 23%. A limitation of our analysis was the dependence on MarketScan Medicaid data in lieu of the availability of specific expenses of the subjects participating in the BABY HUG study. Medicaid data may understate costs of care; based on prior analyses, we estimate that costs to private payers may be 20–30% greater than Medicaid reimbursements. We conclude that increased use of hydroxyurea treatment in children with SCA can lead to significant medical cost savings. Disclosures: Off Label Use: Hydroxyurea is not indicated for treatment of children with sickle cell disease. Use of this medication was for clinical indications and not mandated by this observational study.

Abnormalities of the central nervous system in very young children with sickle cell anemia

1998 ◽  
Vol 132 (6) ◽  
pp. 994-998 ◽  
Author(s):  
Winfred C. Wang ◽  
James W. Langston ◽  
R.Grant Steen ◽  
Lynn W. Wynn ◽  
Raymond K. Mulhern ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Young Children ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Very Young Children ◽  
The Central Nervous System
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