Discussion
It is important for patients with sickle cell anemia prescribed HU to achieve a high HbF and maximal tolerated dose. A recent randomized controlled trial demonstrated that titration to maximal tolerated dose of 29.5mg/kg/day is clinically superior to fixed dose HU at 19.2mg/kg/day dosing and associated with an almost 50% higher HbF level.3 While our clinical program identified lower levels of HU response than randomized clinical trial data, our data did not demonstrate a systematic barrier to achieving a high HU dose and high HbF response based on the use of telehealth dosing or for aggregate socioeconomic data. However, we identified one potential systematic barrier for our satellite clinics to implementing a strategy to achieve a higher HU response. The total number of clinic visits a patient completed in a year was associated with a better HU response. The academic center has the ability to reschedule patients on a near daily basis; however, we conduct satellite clinics monthly to every three months depending on the satellite clinic location. Therefore, improving HU response by targeting more frequent clinic visits may remain a systematic barrier for institutions that conduct outreach sickle cell clinics at scheduled intervals. Promising approaches for satellite clinics would be to incorporate additional telemedicine videoconferences to review HU adherence or apply novel pharmacokinetic technology that can identify an initial maximal tolerated dose rather than dose titration at interval clinic visits.
Patients that admit to poor adherence present a unique challenge to dosing of HU at institutions that titrate to a maximal tolerated dose by targeting mild myelosuppression. Clinicians can either increase a dose of HU despite admitted poor adherence or promote adherence prior to making dose adjustments for myelotoxicity. At our institution, clinicians may defer dose adjustment aimed at mild myelosuppresion until adherence improves. However, without a systematic approach to improve adherence, our center likely maintains lower dosing and lower HbF response as compared to other centers. Recent advances in technology have been developed and tested in pilot studies to improve patient adherence.9-12 These strategies present novel opportunities to improve adherence in centers currently lacking a standardized approach to improved adherence.
Literature has demonstrated the association of poverty, negative socioeconomic factors and poor health outcomes in children.13-15 Our data show that our sickle cell patients cared for in our satellite clinics live in zipcodes with lower socioeconomic indicators. This highlights the need to improve adherence to HU at maximal tolerated dose in order to reduce disparities in acute care for children living with sickle cell anemia in rural or lower socioeconomic neighborhoods without immediate access to local pediatric hematology experts. Our data shows similar HU dosing and response to therapy utilizing a telehealth monitoring of laboratory values with phone call dose adjustments by a nurse clinician. Therefore, interventions to improve adherence to HU in Alabama can be developed and tested in satellite clinics using telehealth HU dose adjustments.
While our data demonstrated that telehealth dosing allowed a similar level of HU response among academic and satellite clinic patients, our study has a few limitations worth noting. To determine hospitalizations and ED visits, we abstracted data from patient recall in the clinic note and our institutional EMR. Our data showed a similar number of hospitalizations between academic center and satellite clinic patients but a higher number of acute care visits among academic center patients. This may represent recall bias of acute care visits among satellite clinics as we do not confirm interval history of acute care visits with local emergency care centers. However, we often receive records or transfers to our hospital for patients admitted with a sickle cell event. Second, we were unable to accurately determine from the medical records whether a patient was continued at a HU dose despite a higher ANC based on poor adherence. Therefore, we could only provide anecdotal evidence that some clinicians in our practice do not aggressively titrate HU in the setting of admitted poor adherence. Finally, we do not collect patient specific socioeconomic indicators as standard of care and therefore relied on zipcode to perform aggregate data analysis.
As acceptance and HU usage increases at academic centers, research must continue to focus on ensuring dissemination of HU to patients with sickle cell living in rural areas. This data suggests that telehealth or telemedicine capacity can be implemented to monitor and titrate HU therapy in rural populations. Clinicians should not be deterred from implementing a telehealth strategy in rural areas or consider the lack of immediate access to lab results a barrier to telehealth. Future data can also evaluate outcomes of HU dosing response at academic centers implementing telehealth during the COVID-19 pandemic.