TY - JOUR
T1 - Evaluation of Longitudinal Pain Study in Sickle Cell Disease (ELIPSIS) by patient-reported outcomes, actigraphy, and biomarkers
AU - Pittman, Debra D.
AU - Hines, Patrick C.
AU - Beidler, David
AU - Rybin, Denis
AU - Frelinger, Andrew L.
AU - Michelson, Alan D.
AU - Liu, Ke
AU - Gao, Xiufeng
AU - White, Jennell
AU - Zaidi, Ahmar U.
AU - Charnigo, Robert J.
AU - Callaghan, Michael U.
N1 - Funding Information:
The authors acknowledge all patients and individuals who contributed to the study. They also thank Sanguine BioSciences, Clinical Ink, and CRF Health for their expertise and efforts to make this study possible. Editorial assistance was provided by Teri O'Neill of Peloton Advantage, LLC, an OPEN Health company, and funded by Pfizer Inc.
Funding Information:
Conflict-of-interest disclosure: D.D.P., D.B., D.R., and R.J.C. are employees of Pfizer Inc. P.C.H., K.L., X.G., and J.W. are employees of Functional Fluidics. A.L.F. has received grants from Argenx, Baxalta, Eisai, Eli Lilly & Daiichi Sankyo, Ionis, Ironwood, Medtronic, Pfizer, and Sysmex; and has received grants and personal fees from Surface Oncology. A.D.M. has received grants from Argenx, Baxalta, Eisai, Eli Lilly & Daiichi Sankyo, Ionis, Ironwood, Medtronic, Pfizer, and Sysmex; has received personal fees from AstraZeneca; and has received grants and personal fees from Surface Oncology. A.U.Z. has received personal fees from Novartis; is on a speakers bureau and has received grants and personal fees from Global Blood Therapeutics; and has received personal fees from Emmaus Medical. M.U.C. has received grants and personal fees from Bayer, Biomarin, Global Blood Therapeutics, HEMA Biologics, Kedrion, Octapharma, Pfizer, Roche/Genentech, Sanofi/Bioverativ, Spark Therapeutics, and Takeda.
Publisher Copyright:
© 2021 American Society of Hematology
PY - 2021/4/15
Y1 - 2021/4/15
N2 - Clinical trials in sickle cell disease (SCD) often focus on health care utilization for painful vaso-occlusive crises (VOCs). However, no objective, quantifiable pain biomarkers exist, pain is not specific to VOCs, health care utilization varies between patients, unreported at-home VOCs likely contribute to long-term outcomes, and patient-reported outcomes are seldom considered. This noninterventional, longitudinal, 6-month study aimed to develop tools to identify VOCs in SCD patients with or without health care utilization. Participants wore an actigraph device, tracking sleep and activity. Patients with SCD used an electronic patient-reported outcome (ePRO) tool to collect data on pain, medication, fatigue, and daily function. Patients self-reported when they experienced VOC pain (VOC day). Biomarkers were collected every 3 weeks (non-VOC). Self-reported VOCs triggered at-home or in-hospital blood collection. The study enrolled 37 participants with SCD; 35 completed the study. Participants reported 114 VOC events and 346 VOC days, of which 62.3% and 78.3%, respectively, were self-treated at home. The ePRO and actigraphy captured end points of pain, functionality, fatigue, activity, and sleep; each was significantly altered on VOC days compared with non-VOC days. Biomarkers collected at home or in the hospital on VOC days were significantly altered compared with non-VOC baseline values, including leukocyte-platelet aggregates, microfluidic-based blood cell adhesion, interleukin-6, C-reactive protein, interleukin-10, tumor necrosis factor-α, and thrombin–antithrombin. The Evaluation of Longitudinal Pain Study in Sickle Cell Disease (ELIPSIS) trial shows the feasibility of accurately monitoring out-of-hospital pain by using patient-reported VOC days as potential end points for clinical trials in SCD; it describes the changes in biomarkers and activity measured by actigraphy that may enable improved identification and assessment of VOCs.
AB - Clinical trials in sickle cell disease (SCD) often focus on health care utilization for painful vaso-occlusive crises (VOCs). However, no objective, quantifiable pain biomarkers exist, pain is not specific to VOCs, health care utilization varies between patients, unreported at-home VOCs likely contribute to long-term outcomes, and patient-reported outcomes are seldom considered. This noninterventional, longitudinal, 6-month study aimed to develop tools to identify VOCs in SCD patients with or without health care utilization. Participants wore an actigraph device, tracking sleep and activity. Patients with SCD used an electronic patient-reported outcome (ePRO) tool to collect data on pain, medication, fatigue, and daily function. Patients self-reported when they experienced VOC pain (VOC day). Biomarkers were collected every 3 weeks (non-VOC). Self-reported VOCs triggered at-home or in-hospital blood collection. The study enrolled 37 participants with SCD; 35 completed the study. Participants reported 114 VOC events and 346 VOC days, of which 62.3% and 78.3%, respectively, were self-treated at home. The ePRO and actigraphy captured end points of pain, functionality, fatigue, activity, and sleep; each was significantly altered on VOC days compared with non-VOC days. Biomarkers collected at home or in the hospital on VOC days were significantly altered compared with non-VOC baseline values, including leukocyte-platelet aggregates, microfluidic-based blood cell adhesion, interleukin-6, C-reactive protein, interleukin-10, tumor necrosis factor-α, and thrombin–antithrombin. The Evaluation of Longitudinal Pain Study in Sickle Cell Disease (ELIPSIS) trial shows the feasibility of accurately monitoring out-of-hospital pain by using patient-reported VOC days as potential end points for clinical trials in SCD; it describes the changes in biomarkers and activity measured by actigraphy that may enable improved identification and assessment of VOCs.
UR - http://www.scopus.com/inward/record.url?scp=85103717435&partnerID=8YFLogxK
U2 - 10.1182/blood.2020006020
DO - 10.1182/blood.2020006020
M3 - Article
C2 - 33067606
AN - SCOPUS:85103717435
SN - 0006-4971
VL - 137
SP - 2010
EP - 2020
JO - Blood
JF - Blood
IS - 15
ER -