Relapse-free survival is progressively shortened in a subset of Black patients with immune-mediated TTP treated in the rituximab era

Immune thrombotic thrombocytopenic purpura (iTTP) is a chronically relapsing disorder caused by autoantibody-mediated deficiency of ADAMTS13. Rituximab is frequently administered to prevent relapses, but whether the durability of rituximab effect is maintained with subsequent treatment courses has not been studied. Using the United States Thrombotic Microangiopathy Consortium (USTMA) retrospective iTTP registry, we evaluated clinical relapse-free survival (RFS) with subsequent courses of rituximab treatment in multiply relapsing patients. Separately, we evaluated overall RFS (composite of time to clinical relapse, ADAMTS13 relapse, or preemptive rituximab) in a prospective iTTP cohort from the Johns Hopkins University and the University of Minnesota. In the USTMA registry, median clinical RFS was shorter after the second or subsequent rituximab-treated episode than the first (2.1 vs 6.0 years; P = .04). White patients' clinical relapse risk after the second and subsequent rituximab courses was not significantly different compared with the first (hazard ratio [HR], 1.86; 95% confidence interval [CI], 0.22-15.80; P = .57), whereas for Black patients, clinical relapse risk was significantly higher after the second or subsequent courses (HR, 2.82; 95% CI, 1.52-5.24; P = .001). In the prospective cohort, overall RFS progressively shortened after each episode of rituximab treatment with the first episode having the longest RFS (2.8 years; interquartile range, 2.0-6.0) and this loss of response durability was most pronounced in Black patients. The durability of rituximab's effect declines with subsequent treatments, which is more pronounced in Black patients, who may benefit from closer monitoring and alternative immunomodulatory approaches such as maintenance rituximab and consideration of other agents.

Authors

Institutions

Publication Details

Journal
Blood Advances
Published
2024-12-03
DOI
https://doi.org/10.1182/bloodadvances.2024013313
Citations
3
Primary Topic
Complement system in diseases
Type
article
Field-Weighted Citation Impact
0.72

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Relapse-free survival is progressively shortened in a subset of Black patients with immune-mediated TTP treated in the rituximab era

Michael D. Evans, Ayotola Fatola, Jay S. Raval, Jenna Brown et al.
3 citations
Blood Advances
Complement system in diseases
0.72
article

Relapse-free survival is progressively shortened in a subset of Black patients with immune-mediated TTP treated in the rituximab era

Michael D. Evans, Ayotola Fatola, Jay S. Raval, Jenna Brown, Susan Eubanks, Radhika Gangaraju, Ara Metjian, Todd Clover, X. Long Zheng, Yara A. Park, Ronald S. Go, Frank Akwaa, Darla Liles, Keith R. McCrae, Nicole K. Kocher, Ming Y. Lim, Meera Sridharan, Ryan Woods, Shruti Chaturvedi, Gustaaf de Ridder, Andrew M. Farland, J. Evan Sadler, Spero R. Cataland, Andrew D. Johnson, Raj S. Kasthuri, Ana G. Antun, Marshall Mazepa, Camila Masias, Lisa Baumann Kreuziger, Harsh Vardhan Upreti, Briana Gibson, Elizabeth E. Davis
article en
3 citations

Abstract

Immune thrombotic thrombocytopenic purpura (iTTP) is a chronically relapsing disorder caused by autoantibody-mediated deficiency of ADAMTS13. Rituximab is frequently administered to prevent relapses, but whether the durability of rituximab effect is maintained with subsequent treatment courses has not been studied. Using the United States Thrombotic Microangiopathy Consortium (USTMA) retrospective iTTP registry, we evaluated clinical relapse-free survival (RFS) with subsequent courses of rituximab treatment in multiply relapsing patients. Separately, we evaluated overall RFS (composite of time to clinical relapse, ADAMTS13 relapse, or preemptive rituximab) in a prospective iTTP cohort from the Johns Hopkins University and the University of Minnesota. In the USTMA registry, median clinical RFS was shorter after the second or subsequent rituximab-treated episode than the first (2.1 vs 6.0 years; P = .04). White patients' clinical relapse risk after the second and subsequent rituximab courses was not significantly different compared with the first (hazard ratio [HR], 1.86; 95% confidence interval [CI], 0.22-15.80; P = .57), whereas for Black patients, clinical relapse risk was significantly higher after the second or subsequent courses (HR, 2.82; 95% CI, 1.52-5.24; P = .001). In the prospective cohort, overall RFS progressively shortened after each episode of rituximab treatment with the first episode having the longest RFS (2.8 years; interquartile range, 2.0-6.0) and this loss of response durability was most pronounced in Black patients. The durability of rituximab's effect declines with subsequent treatments, which is more pronounced in Black patients, who may benefit from closer monitoring and alternative immunomodulatory approaches such as maintenance rituximab and consideration of other agents.

Blood AdvancesVol. 9(2)
University of North Carolina at Chapel Hill (US), Baptist Hospital of Miami (US), Geisinger Medical Center (US), University of Minnesota (US), Cleveland Clinic (US), Mayo Clinic (US), Johns Hopkins University (US), Emory University (US), University of New Mexico (US), Duke University (US), East Carolina University (US), Medical College of Wisconsin (US), Washington University in St. Louis (US), University of Utah (US), University of Minnesota System (US), University of Alabama at Birmingham (US), Baptist Health South Florida (US), Versiti Blood Center of Wisconsin (US), University Pathologists (US), Mayo Clinic in Arizona (US), University of Kansas Medical Center (US), St. Charles Medical Center (US), Johns Hopkins Hospital (US), Wake Forest University (US), The Ohio State University (US), University of Rochester (US), The University of Texas Southwestern Medical Center (US), University of Colorado Denver (US)
University of Minnesota, National Institutes of Health, University of North Carolina at Chapel Hill, National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences
Good health and well-being
Openalex Percentile: Top 28%
Complement system in diseases
0.72
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.