Etanercept plus methylprednisolone as initial therapy for acute graft-versus-host disease.
Graft-versus-host disease (GVHD) is a principal cause of morbidity following allogeneic hematopoietic cell transplantation (HCT). Standard therapy for GVHD, high-dose steroids, results in complete responses (CRs) in 35% of patients. Because tumor necrosis factor-alpha (TNFalpha) is an important effector of experimental GVHD, we treated patients with new-onset GVHD with steroids plus the TNFalpha inhibitor etanercept on a previously reported pilot trial (n = 20) and a phase 2 trial (n = 41). We compared their outcomes with those of contemporaneous patients with GVHD (n = 99) whose initial therapy was steroids alone. Groups were similar with respect to age, conditioning, donor, degree of HLA match, and severity of GVHD at onset. Patients treated with etanercept were more likely to achieve CR than were patients treated with steroids alone (69% vs 33%; P < .001). This difference was observed in HCT recipients of both related donors (79% vs 39%; P = .001) and unrelated donors (53% vs 26%; P < .001). Plasma TNFR1 levels, a biomarker for GVHD activity, were elevated at GVHD onset and decreased significantly only in patients with CR. We conclude that etanercept plus steroids as initial therapy for acute GVHD results in a substantial majority of CRs. This trial was referenced at www.clinicaltrials.gov as NCT00141713.
Levine
John E
JE
Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA. jelevine@umich.edu
Paczesny
Sophie
S
Mineishi
Shin
S
Braun
Thomas
T
Choi
Sung W
SW
Hutchinson
Raymond J
RJ
Jones
Dawn
D
Khaled
Yasser
Y
Kitko
Carrie L
CL
Bickley
Daniel
D
Krijanovski
Oleg
O
Reddy
Pavan
P
Yanik
Gregory
G
Ferrara
James L M
JL
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000097:blood; D004359:Drug Therapy, Combination; D000068800:Etanercept; D005938:Glucocorticoids / Q000627:therapeutic use*; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007223:Infant; D007938:Leukemia / Q000628:therapy; D008223:Lymphoma / Q000628:therapy; D008775:Methylprednisolone / Q000627:therapeutic use*; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D016207:Cytokines; D005938:Glucocorticoids; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D000068800:Etanercept; D008775:Methylprednisolone