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. 2008 Feb 15;111(4):2470-5.
doi: 10.1182/blood-2007-09-112987. Epub 2007 Nov 27.

Etanercept Plus Methylprednisolone as Initial Therapy for Acute Graft-Versus-Host Disease

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Free PMC article

Etanercept Plus Methylprednisolone as Initial Therapy for Acute Graft-Versus-Host Disease

John E Levine et al. Blood. .
Free PMC article

Abstract

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.

Figures

Figure 1
Figure 1
Time to CR for patients with GVHD treated with steroids alone or etanercept plus steroids. (A) Time to CR for all patients with GVHD treated with steroids alone (n = 99; dotted line) or etanercept plus steroids (n = 61; solid line). (B) Time to CR for patients who underwent related-donor HCT treated with steroids alone (n = 53) or with etanercept plus steroids (n = 42). (C) Time to CR for patients who underwent unrelated-donor HCT treated with steroids alone (n = 46) or with etanercept plus steroids (n = 19). The 95% confidence intervals for CR rate at 4 weeks are shown as error bars in panels A to C. Overall survival curves through 6 months from initiation of GVHD treatment by treatment group for all patients (D), patients who underwent related-donor HCT (E), and patients who underwent unrelated-donor HCT (F). The 95% confidence intervals for survival at 6 months are shown as error bars in panels D to F.
Figure 2
Figure 2
Mean TNFR1 plasma levels at initiation of GVHD treatment and 4 weeks later. Mean TNFR1 plasma levels were significantly lower in patients without GVHD (□; n = 190) at time points similar to the onset of GVHD (■) compared with patients treated with steroids alone (n = 99) and etanercept plus steroids (n = 61; P < .001). At 4 weeks after initiation of treatment, mean TNFR1 plasma levels in patients in CR (formula image) were significantly lower than at initiation of treatment both in patients receiving steroids alone (33 of 99; 33%) and patients receiving etanercept plus steroids (42 of 61; 69%). Mean TNFR1 plasma levels (formula image) were unchanged in patients not in CR in both patients treated with steroids alone (66 of 99; 67%) and patients treated with etanercept plus steroids (19 of 61; 31%). Error bars are mean plus or minus SEM.

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