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.